GENERAL MEDICAL COUNCIL
FITNESS TO PRACTISE PANEL (MISCONDUCT)
Thursday 3 April 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
WAKEFIELD, Dr Andrew Jeremy
WALKER-SMITH, Professor John Angus
MURCH, Professor Simon Harry
(Transcript of the shorthand notes of T. A. Reed & Co.
Tel No: 01992 465900)
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
ANDREW JEREMY WAKEFIELD
Examined by MR COONAN, Continued 1
THE CHAIRMAN: Good morning, all of you. Good morning, Dr Wakefield. Mr Coonan, you were in the middle of examination in chief for Child 12.
MR COONAN: Sir, that is right. Thank you.
ANDREW JEREMY WAKEFIELD
Examined by MR COONAN, Continued
Q Last night I was in the Royal Free notes and we had looked, albeit briefly, at the outpatient appointment on 18 October at page 12. Would you go to page 68, Dr Wakefield, there is a letter dated 20 October 1996. In fact, as we shall see in a minute, it is the first of two letters written on the same day by Mrs 12, one to Professor Walker-Smith and one to you, and I shall look at both in turn. Looking at this one first, from Mrs 12 to the professor:
“I am writing follow [Child 12’s] visit to the Royal Free Hospital last Friday 18 October 1996”.
That is obviously a reference to the outpatient appointment:
“My husband and I have thought long and hard about this situation since the appointment. We have also re-read Dr Wakefield’s proposed clinical and scientific study notes.”
I will come back to that in a minute. She sets out some of her concerns in relation to the gastrointestinal problem, and then the third paragraph reads:
“Obviously I do not wish to put my son through any procedures unnecessarily …”
Then, finally, the last paragraph:
“I keenly await the results of the blood tests and if you feel they warrant further investigations my husband and I are happy for him to be referred on to Dr Wakefield’s study project. As you pointed out, it might not help  but if not hopefully it will be of benefit to others.”
That is obviously a letter from Mrs 12, as I said, to Professor Walker-Smith: can I ask you about two aspects of that? First of all, were the results of the blood tests a matter upon which you would have to make any judgement?
Q The phraseology, I am looking at the last paragraph: “… happy for him to be referred on to Dr Wakefield’s study project”, I appreciate it is her phraseology but it is necessary from time to time to ask for your view about other people’s phraseology: what do you say about that?
A I think if one goes back to the first paragraph, she has clearly been supplied (not by us, that is not by Professor Walker-Smith or myself) with the document, the proposed clinical and scientific investigation and I think as it turns out this was provided to her in draft form by Mr Barr. This was unknown to me but, clearly, she took from this that this was in some way my – or exclusively or predominantly – study project, and that is reflected, I believe, in that last paragraph.
Q So it may be timely therefore to look at the route by which she obtained, as she describes them, the clinical and scientific study notes, so I am now going to go into volume 1 of the Panel bundle at page 246. The letter we were looking at was dated 20 October 1996, and this letter is dated 14 October, from Richard Barr to Mrs 12:
“As requested, I am enclosing a copy of the Proposed Clinical and Scientific Study, as requested by you recently.”
It comments that the information is confidential.
If you turn then to page 247, that is the document that Mr Barr enclosed with that letter: does that accord with the point you were making a few minutes ago?
A Yes, it does.
Q You have used the word “draft”, again, I do not want to go through a tiresome exercise but just two references, page 249, is there unfinished business on that page?
A Yes, clearly, five lines down there are missing details on Dr Dhillon’s contact details.
Q And on page 255?
A There are annotations by me between the first and second paragraphs.
Q If others wish to ask you about that point then no doubt they will but perhaps I could deal with it in this way: at that stage was the document in draft form?
A Yes, it was.
Q I said there were two letters of 20 October, and so would you now look at the other letter addressed to you, which is at page 266 of volume 1, from Mrs 12 to yourself. Perhaps we should remind ourselves of some of the contents of this letter:
“Following our first communication in the middle of July this year, [child 12] has at last been seen by Professor John Walker-Smith. His appointment was last Friday, 18 October 1996. Professor Walker-Smith took some blood … for analysis but did not feel sure that [child 12] would need referring to yourself for further investigations. His main reasons were the absence of blood in the faeces and the lack of diarrhoea.
Both my husband and I found the lead up to the appointment quite stressful … At the time we did tell Professor Walker-Smith …”
And she sets out the gastro-intestinal details, which I will not read out, and in the fourth paragraph she says:
“The appointment with Professor Walker-Smith was left such that I should call the hospital in two weeks time and see what the blood test results showed. If there are any positive indicators then I think [child 12] will be referred to you for further tests – have I understood the situation correctly?”
I want to pause there: did she understand the situation correctly?
A I believe that Professor Walker-Smith may have told her that as part of my contribution to this there may be analysis of biopsies in a research setting if a colonoscopy and biopsy was undertaken and that may be what she is referring to here.
Q “Both my husband and I are happy for [child 12] to undergo these tests as we feel there is a problem somewhere in this area. I am sure children of his age do not usually soil themselves every day as he does. I know you are very busy, but you are able to telephone me at some point to discuss this further I would greatly appreciate it.”
Did you telephone her?
A I do not remember but it is likely that I did.
Q Is there any reason why you should not?
A None at all. She had asked me to and I am happy to oblige.
Q “Finally, I would like to say how nice it was to meet you at the JABS open meeting on 4 October in London. I found your short discourse both informative and interesting. I wish you all the best with your research.”
Help the Panel, Dr Wakefield, would you, about the JABS open meeting at which you attended on 4 October: what was your purpose in going there?
A I believe that I had received an invitation to give a presentation to a group of parents and professionals, which I was happy to accept, and which, clearly, I did.
Q What was the subject matter of the presentation?
A I do not remember precisely but it will have been the sort of story that I have told the Panel; it will have been an historical reference to how I came to look at inflammatory bowel disease, at the association with measles, the possible association with vaccination and the emergence of what appeared to be a new condition in children, that is autism or regressive autism associated with gastrointestinal problems.
Q To what extent did MMR feature in that presentation?
A Latterly, towards the end of the presentation MMR will have featured quite strongly because it was an important factor in the story of autism and bowel disorder.
Q Were any of the clinicians there?
A There will have been other clinicians or other doctors giving presentations, I believe, but I have no memory of who they were.
Q But in relation to, for example, Professor Walker-Smith, or Dr Murch (as he then was), were any of those clinicians present as far as you can remember on this occasion?
A No, they were not.
Q Would you turn to page 116 of the GP records? This is the following day, 21 October 1996, from Professor Walker-Smith to Dr Stuart, GP, a letter which was copied to yourself, and the professor writes:
“Thank you so much for referring [child 12], certainly he seems to fit the spectrum of autism.”
Pausing there: in relation to matters which have unfolded up till now in relation to this child, did you have any input into the formulation if that opinion?
Q “I am interested that he in fact does not have a very significant gastrointestinal symptoms …”
Then he sets out some of the findings, and he goes on:
“Some of the previous children I have had referred to me with autism have had clear-cut gastrointestinal symptoms with quite severe abdominal pain and intermittent bleeding and we have gone ahead with our programme of colonoscopy and intensive investigation. However, in [child 12’s] case there is relatively minor gastrointestinal symptoms, I felt it right to perform a full blood count ESR, CRP and I will discuss further with [Mrs 12] concerning the need for intensive further investigation and if the parents wish us to proceed we could certainly arrange this. For the moment I have told [Mrs 12] to be in touch about the results of the blood tests and I have not given another outpatient appointment.”
Again, in relation to those matters, the end of the letter, the investigations which are identified, would you prospectively have any input into assessing whether or not further investigation would be required?
A No, I would not.
Q There is another letter, of the same date, in the Royal Free notes, so would you turn to page 66, and I should say for the record that that last reference GP 116 is also to be found at RF67. Looking, please, at page 66, Professor Walker-Smith writes to you:
“It is interesting to see this child who really has the features of autism …”
Again, did you have any input into the formulation of that opinion, as it were, being written to you?
“… but rather minimal gastrointestinal symptoms. I did not feel it right in facto to proceed with our intensive programme at the moment until we have had ethical committee approval and it is clear that the parents wish us to proceed.”
Leaving aside the question of parental wish, when you received this letter in October 1996 what did you understand Professor Walker-Smith to be referring to when he said that he did not feel it right to proceed with “our intensive programme … until we have had ethical committee approval…”?
A I am not certain. I think when one takes this previous letter into context, that he has clearly assessed this child and is clearly assessing the children very much on an individual basis. There is no blanket approach to these children. They are assessed according to their clinical presentation and the merits of whether they require further investigation. As to the reference to ethical approval, I cannot answer that and I think I will leave that to Professor Walker-Smith.
Q In relation to your reaction to it, and looking at the conceptual approach which you have given to the Panel, does that sit easy with that?
A My perception of ethical approval was twofold. One was under EPC 162-95. It was permitted to conduct research on intestinal biopsies taken during routine colonoscopy. Under 172-96, biopsy analysis was also included but there were other research elements in which I was involved; for example, complement genetics and studies of vitamin B12 metabolism. It was my understanding that we were seeking ethical approval, at least from my perspective, for the conduct of those additional research studies for the correlation of any research findings with clinical findings for the purpose of publication. So there was no need at any stage to have ethical approval for clinically indicated investigations.
Q A month later, Professor Walker-Smith wrote again to Mrs 12, and you will find this at page 38. It is 25 November. The professor writes to Mrs 12 in these terms – I will not read it all out.
“Many thanks for your letter of 20 October.”
We have looked at that.
“I have now got back the blood tests. One was slightly abnormal. As I see that you are keen for us to proceed with investigation I think it would be appropriate for us to arrange for Child 12 to come in for a colonoscopy. I explained in the outpatients what this involved.”
And he sets out the explanation.
“The children are usually admitted for the course of a week and various other aspects of the protocol are undertaken. If you would like us to proceed … please let my secretary know…”.
Did you have any role to play in the assessment of the blood tests when they came back?
A No, I did not but I should say, and this is entirely in accordance with Professor Walker-Smith’s earlier intention. He had conducted screening blood tests. One was abnormal. By that stage the parent had written elucidating in further detail her son’s gastrointestinal symptoms. The parents are keen and therefore Professor Walker-Smith was acting entirely in accordance with his previous recommendation.
Q Would you turn the page back to page 37, in view of this quite quickly, Mrs 12 tells Professor Walker-Smith that she would like the investigation to go ahead, asks him about the nature of the blood test abnormality and then, at page 35, on 27 December, Professor Walker-Smith is writing to Mrs 12, setting out what the slight abnormality of the blood test was and says that Child 12, as he understood it, was coming in to have a colonoscopy. Dr Wakefield, did you play any part in the decision of a colonoscopy at any stage as these months are unfolding?
Q The child was admitted on 6 January. We can see that on page 19 of the Royal Free notes. Did you take any part in the admission process?
Q And there were, following a plan which we can see on page 21, a number of investigations to be carried out. Do you see half-way down the page?
Q Signed by Dr Davey with the code 004.
“PLAN 1. Bloods
3. Barium meal & follow through
It would appear that that plan was noted on the 6th. Did you take any part in the formulation of that plan?
Q In relation to the individual investigations, either at that time or at any stage up to and including the time The Lancet paper was published, did you have an opinion one way or the other about the nature of these investigations?
A I felt they were entirely clinically indicated.
Q We can see if we go back to page 21, if you drop down towards the bottom of the page, Dr Davey has at a ward round with Professor Walker-Smith set out three things. First of all, the result of a colonoscopy, the fact that he was not to have MRI or LP and that on Wednesday there would be the barium meal. As a matter of fact, this child did have a lumbar puncture and MRI according to the documents. Just keep a finger on page 21 and turn into page 34. I am going to proceed on the basis that this child did have MRI and LP. Did you have any part in any decision that this child subsequently has an MRI or LP?
Q Did you cause this child to undergo a lumbar puncture?
Q So far as the range of investigations are concerned, and just leaving aside the additional feature here that the child appears to have undergone procedures contrary to the note on page 21 – leaving aside that point – who did you understand was making decisions in relation to these investigations severally?
A Professor Walker-Smith.
Q One of the types of investigation concerned the EEGs and evoked responses. I would like you now to move on into the Royal Free notes towards the back. You pick this up first of all at page 128. I just want to get our bearings here because a number of these are photocopies of each other on this run of documents. I am going to pick it up, I think, on page 130. First of all, if you look at page 130 there appears to be an overlap with another document. Do you see that?
Q Is that your signature right at the bottom?
Q Is that a signature which relates to the document underneath?
A Yes, it must be.
Q The document underneath, is that page 131?
A I believe it is, yes.
Q Let us look at page 130 first. At the top of the page there is a report. Perhaps we could just do it this way first. The report – do you see the number in the top left-hand corner?
Q F4224. If you turn to page 131, you see the test number F4224?
Q Let us look at page 130 in terms of the request form. Is there any writing on that document which is yours?
Q And if you go back one page to 129, which appears to be the next one up in the overlapping pile?
Q Because of the three lines of doctor’s signature, do you see the test number, top right-hand corner?
Q Any writing on that document yours?
Q Then we go then to 131, a document bearing exactly the same test number and looking at the document as a whole, is that your writing?
A Yes, it is.
Q And just looking at it carefully, is it all your writing?
A No. There are aspects of it at the bottom left-hand column corner there is an annotation which is not mine; the test number is not my writing and in the panel with the tick boxes at the bottom, there are some numbers which, again, are not my writing.
Q What role were you playing here when you completed this form?
A In exactly the way that I had completed these forms with other children, I was acting in a clerking role, having agreed if a test was ordered by the clinicians – this test in particular – then I would arrange that with the department.
Q So far as the reason for the request is concerned, on this document, you have written “Autistic spectrum disorder + bowel disorder following MMR.” What was that entry intended to convey?
A This, again, was a provisional diagnosis, a working differential diagnosis. I think by that stage, it was emerging after having seen twelve children, or at least eleven children by this stage, that autistic spectrum disorder, a broader term rather than disintegrative disorder, was more appropriate and that may be the reason for the change.
Q Following this child, we can look briefly, please, at a number of pieces of correspondence. First of all, if you look in the Royal Free notes at page 31, this is a letter from Professor Walker-Smith to the GP, Dr Stuart. It is 25 April 1997. It is copied to you. The professor tells Dr Stuart:
“We have had quite a remarkable success with the use of Sulphasalzine or 5ASA derivatives in children with autism and evidence of lymphoid nodular hyperplasia and non-specific colitis as we found in Child 12. I think it would be appropriate to consider a therapeutic trial of one of these agents, these drugs appear not only to help gastrointestinal symptoms but also rather surprisingly helped behavioural symptoms. I have therefore suggested that you might consider a therapeutic trial of Olsalazine…”.
It sets out the dosage. Dr Wakefield, from your standpoint, why might you have been interested in receiving a copy of that document?
A Quite apart from my continue interest in the clinical well-being of these children, we were, as I mentioned yesterday, in the process of planning a clinical trial. I had offered, with the research liaison nurse, Ms Thomas, to conduct a semi-formal follow-up of these children in order to assess whether their parents considered there to be benefit or not as part of the possible justification for such an experimental trial.
Q A couple of weeks later, if you go to page 30, Mrs 12 wrote to you on 3 May 1997. She says:
A small point: any significance in the fact she addressed you as “Andy” rather than “Dr Wakefield”?
A Actually it is not a small point, but I do not want to go into too much detail. She will have asked me, “How should I address you”. My response will have been instinctive, but it has to be seen against the background of these parents’ experience with the medical profession. There had, for many of them, been a degree of loss of trust, if you like, a loss of faith in the medical profession who they felt, for one reason or another, and no blame attached, had been unable to deal with their children’s problems. If I had said, “I would like you to address me as Dr Wakefield,” I do not think that would have necessarily helped in our relationship, because it would have possibly thrown up the same kind of barrier that had, at least in their perception, caused them problems in the past.
Q You did not find it untoward that she should be using that form of address?
A Not at all.
Q And you did not tell her to change that form of address?
Q She says:
“I am writing with reference to your telephone call three weeks ago. You asked me to contact you again if I had not received an appointment for [Child 12] to be seen again at the Royal Free within a couple of weeks.”
Can you help the Panel with that background in terms of telephone calls and the role you were adopting at that stage?
A I think she was awaiting an appointment and had mentioned this to me, and I agreed to act as her liaison to ensure that such an appointment, which was entirely routine, was made if it was deemed necessary.
Q An appointment as you understood it for what?
A I think this would have been a follow-up outpatient appointment, that is the only appointment I can think.
Q In the second paragraph she says:
“You also said you would be able to write a report for me outlining the bowel inflammation [Child 12] has.”
We can see what she says: “I understand how terribly busy you are …” and so on. Why did you say that you would be able to write a report for her outlining the bowel inflammation that Child 12 has?
A From memory one of Child 12’s clinical problems was faecal incontinence and very, very loose motions over which he had no control at all, and she was spending an enormous amount of money on nappies, disposable nappies, for him. I believe that she wanted a letter of explanation to someone by way of providing those nappies through some system which would reduce the cost to her. That is my understanding.
Q Whatever the reason may have been, did you see it as being your role to write such a report?
A I cannot remember. It certainly was not something that was influential in any way in his outpatient or inpatient clinical management, but I have no evidence that such a report was written and she may in the circumstances have used the discharge summary or a copy of it to communicate the information to whoever was providing the resources for those nappies.
Q Again, in even offering to write a report were you – again, it is my expression and either accept or reject it if you like – in any way going into clinical waters that you ought not to have been?
A No, I did not consider the provision of nappies for his incontinence a matter that was involved in his clinical management at all.
Q If you look at page 26 there is a letter on 25 February 1998 from Jill Thomas the research nurse which is copied to you and addressed to Mr and Mrs 12. There is a reference in the first part of the letter to a visit by Child 12 to the hospital, setting out the results of tests including one result demonstrating evidence of persistent viral infection. Jill Thomas says to Mr and Mrs 12:
“If you need to discuss these further please contact Dr Wakefield. I have passed on your query about gluten free diets to Dr Wakefield.”
Again, can you tell the Panel please what is your role first of all in relation to gluten free diets, if any?
A I had by that stage some experience of the background or the rationale for the use of gluten and casein free diets in the management of children with autism. It was an experimental approach but there were anecdotal reports of efficacy and some clinical trials that had been conducted, particularly in Norway, so I had a background knowledge of the merits of such an intervention and would have been able to and happy to provide that generic information to any parent or anyone who asked about it.
Q Again, any breach as you saw it of the terms of your employment?
A Not at all, I was not prescribing or recommending prescription.
Q Was it appropriate in your view for Jill Thomas to steer Mr and Mrs 12 towards you for any discussion about the immune system?
A Again, I could have provided background information but nothing that was going to influence his clinical management in any way.
Q Prior to that – perhaps we could just highlight it in the unfolding account – on page 27 in October of the previous year she had written to Jill Thomas and had asked the question,
“How are things progressing on the research front? It seems ages since I heard from anyone.”
It may be appropriate for you to describe Jill Thomas’s role.
A Jill Thomas was a highly experienced paediatric nurse who was brought onto the team in two respects. She provided an invaluable service as a liaison between the clinical and research aspects of this, she was a point of contact and a source of information for parents because this was a group of parents that needed an extraordinary level of input and reassurance, ongoing contact and information. In addition and apart from that she was also involved in running the first national registry of paediatric inflammatory bowel disease, a completely separate project.
Q There is another intervention by you that I would like you to comment on. If you turn to page 9 in the Royal Free notes and you take 9 to 11, is your signature and indeed the date on page 11?
Q What is this document?
A This is a report to the Medicines Control Agency about possible adverse reactions to vaccines and it is a confidential report sent to clinicians who had been involved in the child’s care and there is a request for them to complete this and return the document to the Medicines Control Agency.
Q In the course of the proceedings there appears to be a suggestion that you ought not to have been doing this, or if I can turn it the other way why should you be doing it and not a clinician?
A Firstly it is a document that in no way has any impact whatsoever on the inpatient or outpatient management of any child. It is a document that is distilled from the clinical record of that child and there is no direction or requirement for this document to be filled in by a clinician or the clinician in charge of the child’s care – that is number one. Number two – and Professor Walker-Smith may have an opinion on this and I will be corrected if I am wrong – when these were received I was asked by him if I would fill them in. I was very happy to do that, it was in no way a breach of my contract, I did so and they were returned to the Medicines Control Agency.
Q Outpatients clinics: you have given evidence to the Panel about your attendance from time to time at those clinics. Can we look at one illustration, please, if you turn to page 75. I appreciate, as will the Panel, that this is not your document but it appears to be a note of a conversation following the leaving of a message by Mrs 12 on 18 June 1997. The note says – I am looking at the sixth line – “Dr Wakefield will see Mrs 12 in clinic on 4 July.” There are further observations as to what the writer says to Mrs 12 and at the bottom of the entry, “Dr Wakefield is aware of need for report on bowel inflammation.”
Two things: what is the reference to the fact in her words that you will see Mrs 12 in clinic on 4 July? Any comment you want to make about that?
A No, that is likely to have been entirely accurate. As I mentioned earlier I sat in on these clinics and would likely have been present at that one.
Q The reference to a report on bowel inflammation.
A I think this goes back to the issue that was discussed earlier in relation to the request for help in getting nappies for his incontinence.
Q Finally, in relation to the interventions and appointments we move ahead quite a number of years, please, to GP bundle page 26. For current purposes I do not think it is necessary to read out the whole of this document, but on 7 February 2002 you wrote to Mrs 12, we can see from your signature on page 27,
“I am writing to you to give you the results of detailed analysis of Child 12’s biopsy tissue taken at the Royal Free Hospital … This biopsy was done as part of an investigation into your child’s symptoms and the possibility that the measles virus may be playing a part in the inflammation that has produced these symptoms.
The testing was carried out at the Unigenetics Laboratory at the Coombe Women’s Hospital, Dublin by Professor John O’Leary and his team.”
Apart from the scientific explanation set out in that document my question is directed to this: what role are you playing when you are writing to her in 2002?
A What I am doing here is providing the results of the research analysis undertaken on Child 12’s biopsies and that is entirely in line with my role in this issue.
Q Is the report relevant to that which is attached to the letter as we can see at pages 28 and following?
Q Thank you very much. Can I turn from medical matters and research matters to the question of legal aid? There is a reference to legal aid that I would like you to look at in volume 1 of the Panel bundle at page 242. This is a legal aid certificate for Child 12 and for my purposes the only thing I need from this is the date, at the bottom right-hand corner, 9 October 1996. Did you ever get to know that this child had a legal aid certificate?
Q When did you get to know that?
A No, I cannot remember, but as it turns out this is the only child who was, to our knowledge involved in litigation – subsequent knowledge. It turns out that this is the only child who had a legal aid certificate prior to their referral and investigation at the Royal Free Hospital.
Q But at the time of the referral or about the time of the referral and investigation did you know then that he had a legal aid certificate?
A I have no memory of it.
Q Did this child become one of the Legal Aid Board children?
A Yes, I think he did.
Q Did you have any understanding or appreciation of any litigation motivation by the mother at or about the time of referral.
A No, the mother’s motivation is evident in the letters that she has written to Professor Walker-Smith and that is the gastrointestinal symptoms and problems that she felt were present in her child.
Q Can I just turn to the backdrop of the live charges, head of charge 23. In relation to 23(a) and the stem, as with all the other children, and 23(b), the same issue arises, what, as far as you are concerned, research was being carried out in relation to this child?
A Laboratory based analysis of biopsies taken during routine clinical colonoscopy.
Q What about the investigations, colonoscopy, MRI, LP, that we have looked at in the clinical notes?
A No, these were all entirely clinical.
Q So far as inclusion criteria (I am looking at 23(b)(i) and (ii)) were they relevant, so far as you were concerned, in the investigation and management of this child?
Q Consent forms are referred to in head of charge 23(c), would you have expected consent forms in respect of the clinical investigations that you have described?
Q If you go to the Royal Free notes and go to page 77, what is the status of that document?
A This is a Royal Free Hampstead NHS Trust Consent Form for routine investigation, in this instance colonoscopy and biopsy.
Q Is that what you would expect if the investigations were being considered to be clinical?
Q In relation to the biopsies and subsequent laboratory analyses that you have described, would you expect consent forms for that activity?
Q If you turn back to page 76, is that what you would expect for that activity?
A Yes, it is.
Q I omitted to ask, Mr Sheldon reminded me, in relation to the question of clinical investigations on the one hand and the research activity on the other, I forgot to ask you whether you would require ethical committee approval for the research activity.
Q Did you have that?
Q What was that?
Q On the consent form for research biopsies at page 76, is that linked with any EC approval either required or obtained?
A Yes, this is a consent form pursuant to 162/95.
Q Finally this, the Lancet publication, so far as your role in the drafting process is concerned, what materials did you have available?
A As with all the other children, I had the full contemporaneous clinical records. I believe I had some early developmental records from the Red Book and the detailed histopathology proforma designed and completed by Professor Paul Dhillon.
Q Thank you very much, that is all I am going to ask you about child 12 and turn to the last child, child JS. Could I ask you to go the Royal Free notes and the local hospital notes, volume 1? Dr Wakefield, there is no charge in relation to this child so far as you are concerned but there are aspects of the evidence that I am going to invite you to comment on for the assistance of the Panel. Can we start by having the Royal Free records open at page 80, it is a letter dated 16 April 1996, from Mrs JS, and it is written to yourself:
“Dear Dr Wakefield,
Thank you for your telephone call last week. I enclose a record of [JS’s] development and regression following the MMR vaccine.”
The record is slightly out of order but begins at page 79, then you have to jump the letter and start again at page 81, and it runs through to page 92, is that right?
Q Then if we go back to the letter at page 80: how did it come about that there was a telephone call between you and Mrs JS?
A This was one of very many calls that I had received from parents. She will have called me in this instance, and left a message on my answer machine – I am not sure why I was not present at that time but – I will have been responding to her call.
Q What did she tell you?
A Hers was a particularly distressing story, again, her son [JS] had been developing normally and had received a first dose of his MMR vaccine but started having problems. He had had onset, I believe, of developmental changes and onset of gastrointestinal symptoms. He had then at some stage in error received a second dose of the MMR and this comes back to what I described very early in my evidence as a “re-challenge case”, a case that is similar, indeed, to Child 4, and following re-exposure he underwent catastrophic deterioration, losing all residual skills, losing self-help skills, developing progressive faecal and urinary incontinence. He was extremely distressed. One of the features of these children that had been difficult to interpret was abdominal pain because they could not articulate their symptoms in the way that a normal verbal child could and often this manifests as odd posturing, leaning on things, running around, frantic activity – I am sure the Panel have experienced colic and when you have abdominal colic, intestinal colic, it is impossible to stay still. This child was just like that. He was running around. He was impossible to control. He kept escaping from home. The mother was at her wit’s end. It was a very distressing case.
Q Is that what she was able to tell you in that conversation?
A Whether it was all articulated in that conversation or in the letter that she sent as well I do not know, but it was certainly then.
Q I am not going to take you through the detail of the letter. The Panel, if necessary, can read it; others may take you to it but have you had an opportunity of refreshing your memory by reading the letter?
A I have.
Q Is that in accordance with your recall of the general sense of what she was telling you?
A Yes, it is.
Q Did you call her back after receiving the documents?
A I will have called or written. I do not remember but I will have communicated with her in some way, yes.
Q Whether it was either by letter or in another telephone call, were you able to give her any advice?
A Yes, as with all other children, I made it clear to her that if she wanted referral for the investigation of her child’s symptoms, if that is what she wanted then she would need to make contact via her general practitioner with Professor Walker-Smith.
Q So again, how would you describe your role at that stage?
A Again, as with the other children, I was acting as a signpost for this mother for the possibility of her getting care for her child.
Q The next event I would like you help about is later on in April (the same month) on 29 April, because if you turn to page 77 in the Royal Free bundle you will see a letter addressed to you from Dr Mills, consultant community paediatrician, copied to Professor Walker-Smith, Mr & Mrs JS and the GP Dr Shore:
“I understand that you have recently spoken to the mother of this four year old boy who lives in XXX.”
Pausing there, that is correct, is it not?
A That is correct, yes.
Q “You suggested to her on the telephone that a referral to Professor Walker-Smith may be appropriate and Mrs JS has contacted me asking if I would make a referral.”
Is that in accordance with your understanding of what you said to Mrs JS?
A Yes, that puts it really rather well but my suggestion to the mother was that a referral to Professor Walker-Smith may be appropriate – I am not saying it was or was not, simply offering that it may be – and if she felt that was the case then she would need to get a referral. In this case she sought the referral, not from the general practitioner as it turns out but from Dr Mills the community paediatrician.
Q Dr Mills summarises the history that he had in the next paragraph and in the following paragraph:
“The family date JS’s problems to happening after MMR vaccine at the age of 18 months and they are convinced that this is the etiology of his autism.”
The last paragraph on that page:
“Mother has asked me to make a referral to your team. Could you let me know what you would be able to offer …
I am quite happy to be open-minded about unsubstantiated causes and possible future treatments, but I am not keen on sanctioning detailed investigations unless there seems to be some logic behind them.”
Further down the page on this document, which, of course, as we know comes from the Royal Free records, there is some writing: is that your writing?
A Yes, it is.
Q Would you read it out, please?
A It says, “Discussed with Dr Mills: happy to make.”
Q Following this letter that you received, did you have a phone conversation with Dr Mills?
Q Can you remember now who phoned who?
A I would imagine that in accordance with Dr Mills’ request in the last two lines on page 77, asking, “Could you let me know what you would be able to offer [name mentioned] and his family, I will have responded to that ---
THE CHAIRMAN: If there are any new members of the press present please make sure that the anonymity of this child is preserved.
THE WITNESS: My apologies, Mr Chairman: Then in accordance with this request for me to contact him I will have done that.
MR COONAN: If you look at the top of page 78, the fourth line down:
“I look forward to hearing from you.”
Q Can you remember now the precise terms of the conversation with Dr Mills?
A It will have been in exactly the same format as my previous discussions with doctors. It will have been a description of the generic background to our thinking, the collective approach to this particular problem and the reiteration that any referral would need to go – which is noted at the beginning of this letter – to Professor Walker-Smith: not to me, not to my team but to Professor Walker-Smith.
Q As far as the note that you make is concerned, what did that reflect your understanding at the time?
A Based upon the information that I was able to provide to Dr Mills, and based upon the fact that at that time he seemed to be keeping an open mind, he seemed happy to make that referral.
Q Was that note that you have made a contemporaneous note?
A Yes, it was.
Q That was in April 1996, and I am now going to look at some correspondence, as it were, which shifts sideways because I want you to comment on a number of passages. For this exercise we need to look at the local hospital records. This is on 3 June 1996 to the GP from Dr Mills. I am going to take you towards the bottom of, first, page 114.
“The family remain convinced that JS’s problems developed after MMR vaccine and they have been in contact with several other families around the country who believe the same. They have recently tracked down a Dr Wakefield, Gastro-enterologist at The Royal Free Hospital in London. I have discussed the issue with Dr Wakefield myself and his team are undertaking research into measles associated chronic diarrhoea. They have, incidentally, identified several children who apparently have autism as an association and he was very keen to offer JS detailed gastroenterological investigations, including a brain scan in London.”
Then over the page at 115, the second paragraph:
“I have to say I was rather reluctant to refer JS to a far flung centre for gastrological investigation and research. However, I did agree to undertake some blood tests to look for more subtle evidence of malabsorption after which we can reassess the situation. It does seem unlikely that any of this is actually going to help JS’s behaviour or day to day management.”
The point I just want to address with you, Dr Wakefield, is this. The note that you made on page 77, “Discussed with Dr Mills Happy to make”, again looking at what Dr Mills subsequently wrote in June to Dr Shaw, would you help the Panel again, please. What was your understanding at that time that Dr Mills had been saying to you?
A At that time, when we had our telephone conversation, it was my understanding that he was happy to make or to consider the referral. If he had been unhappy to make the referral, I would have written “Unhappy to make”. In the interim ---
Q Sorry. Help the Panel about the word “make”?
A “Make” refers to making a referral to Professor Walker-Smith.
Q Then if we move on to page 142, this is part of a letter from clinical psychologist, Betsy Brua, to Dr Mills. On page 142 there is a passage which I am going to pick up on the third paragraph, under the heading of “Investigations”.
“Mrs JS is still in touch with Dr Wakefield at the Royal Free Hospital who is apparently saying that JS could come in for a week’s investigation which would include a brain scan before Christmas. This would be free of charge.
I was fairly confrontational with Mrs JS about how she dashes from one approach to another and she acknowledges that she is inconsistent. I have also said how little I thought a brain scan would show. She however feels strongly that she wants to pursue the work with Dr Wakefield. I got the impression that she would do it with or without our support.”
Just this. We are now in November. To what extent were you in touch with Mrs JS during the period, the contact having started in our about April?
A Mrs JS, I believe, continued to make contact with me in her increasing desperation to get help for her son, JS, but as to this letter, this is now several degrees removed from anything that I said and I really cannot answer in any way for what was written here.
Q If you turn to page 144. On 6 November Mrs JS wrote to Dr Mills. She says in the third paragraph.
“I have, this week, heard from Dr Andy Wakefield who has sent me the enclosed information about Hellers disease. This sound[s] so much like JS’s history that we find it most alarming.”
I want to look, please, at the information that she tell the community paediatrician, Dr Mills, that she had received from you. Would you turn to page 145 and look at those pages following, 145 to 161. Did you give her or send her that material?
Q The second document which was attached to this letter is a document beginning at page 162 running through to 182. Did you send Mrs JS that document?
A No, I did not.
Q In her covering letter, she refers at page 144 again to “enclosed information about Hellers disease”. Is there a reference in the document beginning at page 145 to Hellers disease?
A Yes, there is.
Q Turn to page 149. Does that relate to Hellers disease?
A Yes, it does.
Q The other document, which in fact is a Dawbarns’ fact sheet, does that relate to Hellers disease?
A It makes no mention of Hellers disease.
Q I want to pause for a moment in the unfolding chronology. JS was not one of The Lancet children, but did you know whether or not this child had Legal Aid?
A Yes, I did.
Q And when did you know that?
A I cannot remember precisely, but the mother will have informed me of that fact, presumably soon after it had been obtained during the period of our correspondence.
Q Have you had any doubt about the suggestion that you supplied the document at 162 to Mrs JS?
A Absolutely not. I did not have these documents.
Q Can I now leave that background material, and move back to the Royal Free records, page 76. On 6 November you wrote to Professor Walker-Smith about this patient, in these terms:
“This is a child that I would like to be included in our study if you consider him suitable. His community paediatrician, Dr Mills, was initially enthusiastic about referring him. He now seems to have gone cold on this. Nonetheless, JS has been awarded Legal Aid, who will pay for the investigations and this is [in] hand. I would be grateful if you would therefore arrange to see him as an outpatient to assess him for possible investigation in our trial.”
Can we just look, please, at a number of the elements of that letter. In the first line you refer to “our study if you consider him suitable”. What are you conveying to Professor Walker-Smith there?
A What I am conveying with the accompanying documents from this mother would be the fact of his problems and the fact that his mother has requested help, that he might be suitable depending on Professor Walker-Smith’s opinion for inclusion in what was our joint clinical and scientific investigation – clinical on the part of Professor Walker-Smith and his team, and scientific on my part.
Q You say as of 6 November that Dr Mills was initially enthusiastic about referring him. Was that true?
A That was my impression, yes.
“He now seems to have gone cold on this.”
Was that your impression at that time?
A It was.
Q And the question of Legal Aid, which you dealt with a few minutes ago. Does it follow that by this stage you knew that he had a Legal Aid certificate?
Q What was the basis for you saying to Professor Walker-Smith that, first of all, he had Legal Aid, and that Legal Aid would pay for the investigations? What were you conveying there?
A This goes back to the terms of the Legal Aid Board pilot study in those circumstances where, for example, a general practitioner was not willing to make an ECR despite the clinical indications being present in a child, as deemed the case by Professor Walker-Smith and his team, in those circumstances there may be funding available from the Legal Aid Board to pay for, for example, an overnight stay, colonoscopy, MRI, EEG.
Q In the next sentence you say that you would be grateful if he, Professor Walker-Smith, would arrange to see him as an outpatient. On what basis would you be saying to Professor Walker-Smith that you would in effect like this patient to be seen at outpatients?
A Again, it goes back to the first line of this letter – “if you consider him suitable”. His suitability would be assessed by Professor Walker-Smith in the outpatients, with the documentary record from the mother, and that is the suggestion that I am making to Professor Walker-Smith.
Q On 7 November, the following day, Professor Walker-Smith writes back to you and says to you, on page 74:
“Many thanks for your letter. If Dr Mills and Mr and Mrs JS are keen for me to see JS, I would be happy to do so.”
It is written directly to you. Is that the sort of response that you would expect Professor Walker-Smith to make?
A Yes. Here Professor Walker-Smith is taking an executive decision, and quite appropriately he feels that both Dr Mills’ and the parents’ agreement to him seeing this child would be necessary.
Q At page 75, Professor Walker-Smith writes to Dr Mills in these terms:
“Dr Wakefield has passed on correspondence concerning JS. Through Dr Wakefield we have been looking at a group of children with autistic symptoms related to MMR vaccine and have found that a significant number of children have had gastrointestinal symptoms.”
Pausing there, was that an accurate description that Professor Walker-Smith uses, that it was, as it were, through you that “we have been looking at a group of children…” et cetera, et cetera?
A Yes. It is accurate to the extent that all of the referrals, I believe, at that stage, the instigation of the request from the parents had been through a telephone conversation or letter to me initially.
Q Then, on the third line:
“When these have been present we have so far found endoscopic abnormalities in all five children we have investigated. I would be quite happy to see Mr and Mrs S and to discuss the situation with them and to indicate what investigations might be appropriate and then to get your advice as to the right [way] for us to proceed.”
Is that the sort of letter you would expect from your standpoint in relation to the role you were playing in these arrangements?
A Yes, I had no part in these arrangements. This was Professor Walker-Smith writing to offer his services to Dr Mills should he require them.
Q I need to look at two letters between Dr Mills and Professor Walker-Smith because these letters bring you into a series of letters with Dr Mills himself. By way of background, could we just look briefly at those two letters. Page 73. On 15 November Dr Mills writes back to Professor Walker-Smith thanking him for his letter. In the first paragraph he says:
“The family made direct contact with Dr Wakefield themselves following information from the JABS Parent Support Group. I have spoken to Dr Wakefield and I consider that JS is not appropriate for the investigation schedule he recommends at present.”
Pausing there, had you had another conversation with Dr Mills?
A I do not think so.
Q How many conversations do you recall having with Dr Mills?
A I think only one.
Q In relation to the investigation schedule as he describes it, it is his use of the word obviously “recommends”, but how did you see it, were you recommending any particular structure or schedule?
A No, certainly not. What I was giving him was a generic background.
“I understand that Dr Wakefield has been continuing to send the family information. In particular, he has been sending them information from a firm of solicitors who seem to specialise in litigation in relation to immunisation.”
Perhaps we can deal with this straightaway, had you been sending the family information from solicitors?
A Absolutely not.
“I agree that your research findings are very interesting … I do not think that your research programme is appropriate for him at present. This … may change and the family may disagree with my views.”
Then in the last two lines he says:
“I am beginning to wonder whether you and your department are rather pressurising this family …”
I want to ask about you personally, Dr Wakefield, and about your department. Were you in any way pressurising this family?
A Not at all, this was a spontaneous call from the mother initially desperately asking for help for her very sick child, and ours was a compassionate response to that in an effort to try and get someone, in this case Professor Walker-Smith, to shed some light on what might be the problem. There was absolutely no pressure whatsoever at any stage from anyone in my group.
Q Professor Walker-Smith responded to that letter and we can pick it up at page 72. I just observe in passing, before we look at the letter, that this reply from Professor Walker-Smith was copied to you, do you see at the bottom of the page?
A I do.
“Many thanks for your letter. I can quite understand you feeling that it may not be appropriate for us to see JS at the moment. However, I would be happy to hear from you again should the position change.
In relation to your last comments, I am certainly doing nothing to pressure the family to see us. In fact, my department is somewhat overwhelmed by the response of parents who believe that their children have autistic and gastrointestinal symptoms following MMR. I personally had no idea that there were such large numbers of patients in the community across the country where the parents have made this association. I am sure Dr Wakefield, who is not actually a member of my own department, would also say the same.”
A I would concur entirely with that letter.
MR COONAN: Sir, maybe you might care to take a break at this stage.
THE CHAIRMAN: Thank you. It is quarter past eleven; we will now have our mid-morning break and resume at 25 to 12. Dr Wakefield, you are still under oath so please do not discuss this case.
MR COONAN: Dr Wakefield, we had been looking together at the correspondence in November 1996 between Professor Walker-Smith and Dr Mills at the Royal Free bundle pages 72 and 73, and you told the Panel that the letter at page 72 had been copied to you. I now want to look, please, at your involvement in the issue that had arisen during that latter correspondence and for these purposes you need to take the local hospital records, volume 1. Could you turn to page 191, please. This letter was from yourself to Dr Mills, is that right?
Q And copied to Professor Walker-Smith. We can deal with it straightaway in the first line:
“Professor Walker-Smith has passed on a copy of your letter to me dated 15 November 1996.”
I think in fact it was addressed directly to Professor Walker-Smith, is that right?
A Sorry, I meant it had passed on to me, yes.
Q Let us look at the body of the letter:
“In it you make several serious allegations. I wish to make it quite clear that I have at no stage sent this family any information from solicitors dealing in litigation in relation to immunisation.”
Was that true?
“Secondly, Mrs JS phoned me initially and has continued to request investigation as part of our protocol.”
Was that true?
“I find the accusation that we are pressurising this family grossly unfair and without any substance whatsoever. Mrs JS, perhaps quite justifiably, has sought inclusion of her son in our investigations. It is our opinion that children with late onset autism such as JS have been under-investigated and their parents’ anxieties often dismissed too readily by those in charge of their care. I look forward to receiving your comments before deciding on how to proceed with this issue.”
Were you upset about this?
A Yes, very.
Q Just share with the Panel, please, why you were upset about it?
A Dr Mills had, without reference back to Mrs JS as to the source of the specific information that she had given to him, and without making contact with me but by writing directly to one of my colleagues, had made serious allegations about me.
Q His reply can be found at page 195:
“Dear Dr Wakefield,
Thank you for your letter. I am sorry if you feel that the information contained in my letter of 15 November [we have looked at that] is inaccurate.
Mrs JS gave me a fact sheet from Dawbarns Solicitors [that would appear to be a reference back to Royal Free records page 162] concerning mumps, measles and rubella vaccine and measles and rubella vaccine. She also gave me a study proposal entitled ‘A New Syndrome: Disintegrative Disorder and Enteritis following Measles/Rubella Vaccination’ with yourself named as the co-ordinating investigator. Mrs JS told me that you had given her both these documents. It is quite possible that she may have been confused about the origin of the document and failed to admit that they had come from separate sources. However, I certainly was led to believe that you were the source of both documents, particularly as the Dawbarns document encourages parents to contact yourself if ‘your child has developed persistent stomach problems (including stomach pains, constipation or diarrhoea) following the vaccination’. The article comments that you are looking into Crohn’s disease.
I apologise if I have incorrectly attributed the source of this document to you.”
So he deals with that issue and then he goes on to deal with the second matter, a matter originally raised with Professor Walker-Smith. He sets out a number of features which he points to. Perhaps I should read it, the top of page 196:
“I fully accept that the family contacted you in good faith and that you encouraged them to discuss with me the possibility of referral to your department for further investigation. I recollect that you and I have spoken on several occasions on the telephone concerning the possibility of referring JS. I have always been interested in your research, but have always been of the view that, given JS’s current clinical state, his lack of any gastroenterological symptoms of any significance and the extensive nature of the investigations that you are recommending, your programme would not benefit JS at present.
As I recollect, I made this view known to you and Mrs JS on a number of occasions. In addition. I have asked one of my paediatric colleagues to review JS and she is of the same view.
In view of all these facts, I was rather surprised to receive a letter from Professor Walker-Smith on 7 November continuing to recommend referral to your department.”
Pausing there, Dr Wakefield, had there been at any stage a recommendation for referral to your department?
A No, there had not.
Q He sets out his opinion: “JS is an extremely difficult child to deal with clinically …” and he sets out the reasons why.
“Like JS’s parents and yourselves, we are desperate to find something that will alleviates both JS’s symptoms and the family’s distress. However, on reviewing your research programme, myself and my paediatric colleagues have felt that this is not what JS needs at the moment.
I hope that you will now take the clinical decision of those people who are currently looking after JS that investigation by your department is, at present, not a pressing need. If JS’s clinical situation should change in the future, or indeed if the results of your investigations indicate that JS may benefit, then I will be happy to change my clinical advice.”
Then your response, to complete this issue, is to be found at page 192:
“Thank you for your letter and comments of 12 February. I appreciate your taking the trouble to respond and I now consider this matter closed.”
That was 19 February 1997 and, as a matter of fact, there had been no referral or admission of this child to the Royal Free.
Q I want now to go back to the Royal Free records and open them at page 71. You may care to have in mind the letter from Dr Mills that I read out significant parts of a few minutes ago at local hospital records page 195. On 16 April 1997 you wrote a letter to Professor Walker-Smith:
“Further to our conversation I would be very grateful if you would reconsider JS for admission and investigation. His behaviour has deteriorated to the extent that he is absconding from home and has been found wandering down the middle of the road, and on one occasion fell into a waterway. The strain on the family is absolutely enormous and I do believe that he is someone that we may be in a position to help. There is legal aid funding to pay for his investigation which I appreciate you will need to discuss with David Leigh. His mother is keen for him to be investigated at your earliest convenience.”
We can obviously look at the content of that, and I need to ask you why in the light of Dr Mills’ letter at page 195 of the local hospital records, given his (Dr Mills’) view, why at this stage some two months later you are inviting Professor Walker-Smith to reconsider JS for admission and investigation. How does that come about?
A At this stage Mrs JS had contacted me again and was beyond desperate. Her son had escaped from the home and escaped death by the grace of God. He had no sense of danger whatsoever and he could not be left unattended for a moment. There was a very real possibility at this stage that he was going to be taken into a permanent placement away from his family. They were desperate for that not to happen, but it seemed inevitable in view of the fact that they could no longer cope. She was convinced that many of his problems arose from his physical symptoms; she could not be absolutely certain but she was sure that he was suffering from pain in association with his diarrhoea and it was a cry de Coeur to me which I was absolutely obliged to pass on to Professor Walker-Smith in any effort that we could make to help this child.
Q When you said in the letter that “we may be in a position to help”, from your standpoint what sort of help might be available?
A I think the only thing on my mind at this stage was acting as a signpost, a conduit, for this child to get clinical care from Professor Walker-Smith.
Q Did you have any idea in your mind at that stage what might possibly be the result of such clinical care if he had access to it.
A Yes, indeed. As with the other children, it may have been possible if it was felt appropriate for investigation and biopsies that we could conduct similar research analysis to see if there was any evidence of viral infection in his intestine.
Q How frequently at this stage did you have contact with Mrs JS?
A I am unable to say precisely but she was calling me on a regular basis.
Q Can you now turn to page 199 in the local records? Professor Walker-Smith writes to Dr Mills on 23 April, you having written to Professor Walker-Smith on 16 April, and this letter is copied to you:
“I am writing to you again as I understand from Dr Wakefield that the family are considerably distressed concerning [JS]. We have begun to have some quite remarkable success in treating children with autism and evidence of bowel inflammation with Sulphasalazine and related drugs. I do believe it really would be helpful for us to do these investigations in [JS] or for me to at least see the child to assess the situation. I enclose a copy of our protocol and would be grateful if you would reconsider this issue once more.”
Professor Walker-Smith can speak for himself, obviously: is that letter the sort of letter that you would have been content to have seen following your conversation with Professor Walker-Smith, or your letter addressed to Professor Walker-Smith?
A Yes indeed, he has responded to my request to him and he has acted in an entirely appropriate manner by contacting Dr Mills again and seeking to offer the help of this department.
Q In the letter Professor Walker-Smith refers to “a copy of our protocol” and next to the letter, at pages 200-203A, there is a document and for these purposes I take it that that is in fact the protocol in this sense that Professor Walker-Smith was referring to?
Q We have not looked at this document, as far as I recall it, during the course of these proceedings. First of all, can you tell the Panel who drafted this?
A This would have been drafted by Professor Walker-Smith and myself.
Q What was the purpose of it?
A This is the document that I have referred to several times before. There had been a series of errors of communication, which I accept, at least in part, responsibility for between the referring doctor’s department such that the letters had gone to the wrong department or to the wrong person and we had decided in order to avoid that for the future we would produce a detailed description, again in a generic sense, of the background to what we were doing and what was intended, and this is in essence what I will have communicated to the general practitioners when we had contact.
Q What, communicated orally?
A Orally, indeed, yes.
Q Since we have not looked at it, what I am going to do is ask you to read this since, as you have said, it is the essence of what you had been saying orally to other GPs. I fully understand the Panel, of course, can read this at their leisure but it is the last patient we are dealing with and it is the opportunity to deal with the essence of what you were saying to them: would you do that, please?
A Certainly, the title:
“Introduction to the rationale, aims and potential therapeutic implications of the investigation of children with classical autism or the autistic spectrum disorder who have gastrointestinal symptoms.
What is the background to this study?
Following publication of data demonstrating a possible link between measles virus, measles vaccination and inflammatory bowel disease (1-6), we have been contacted by an increasing number of parents who have described their children, features both of autistic spectrum disorder (especially ‘late onset’) and also symptoms suggestive of intestinal dysfunction, including pain, diarrhoea, bloating and food intolerance. Behavioural symptoms and signs were reported to parallel intestinal disturbances, and specific foods in some cases appeared to trigger both deterioration in behaviour and gastrointestinal symptoms.
The syndrome of regressive autism occurs when normally developing children suddenly, or over a period of several months, have marked behavioural changes and developmental regression. This is often in association with what has been described as some loss of co-ordination of bowel and bladder function (Reviewed by Rutter et al, 7). Behavioural changes include social withdrawal, reduced response to sounds, complete loss of communication, unusual sensory behaviours and development of simple rituals and hand and finger stereotypes, much like those of classic autistic children. However, regressive autism differs from classic autism by the loss of acquired motor and self-help skills and usually, too, by the lack of more complex stereotype patterns. This disorder can sometimes be linked to measles encephalitis, cerebral lipoidoses or leukodystrophies, but in most cases no cause is ever identified. In those cases reported to us, many parents have consistently and spontaneously linked the onset of MMR vaccination. In a similar series reported from the US, there has been a consistent link with MMR vaccination (8, 9).
Evidence is accumulating for the involvement of immune mechanisms in the pathogenesis of autistic spectrum disorders, including regressive autism. This includes the presence of circulating antibodies to myelin basic protein (10, 11) and the putative brain serotonin receptor (12). Guptha et al noted marked differences in immunological parameters in autistic children compared with age-matched controls (13): these included abnormalities of various lymphocyte subsets, decreased lymphoproliferative responses to mitogens and altered serum levels of various immunoglobulin classes and subclasses (14). Overall ---“
Q Would you just pause with the rather more detailed science, and I invite the Panel to read that at their leisure but I think we can go, can we not, to page 202, to the heading “What does this study hope to achieve”? Would you pick it up there?
“The purpose of this preliminary clinical study is, firstly, to adequately and appropriate investigate the gastrointestinal signs and symptoms manifested by these children: investigation is merited on clinical grounds. It is our experience that these clinical features often have been ascribed to the inevitable consequence of behavioural abnormalities upon bowel function, and as a consequence the children have not necessarily been investigated adequately. It should be stressed, therefore, that the investigations are clinically indicated in all cases that are admitted for evaluation. The validity of this approach is borne out by the fact that most children investigated so far have significant and consistent intestinal pathology (lymphoid nodular hyperplasia and microscopic colitis). Secondly the study is to seek the presence, and to characterise the nature of any intestinal and cerebral pathologies in affected children. In view of the coincident changes in both behaviour and intestinal symptoms we believe that this form of regressive autism and perhaps other behaviour problems within the autistic spectrum may be linked to chronic intestinal inflammation.
It is our aim to investigate and institute appropriate therapeutic measures aimed at controlling the intestinal inflammation and correcting any nutritional deficiencies that may be present. The impact of these measures on behaviour will be monitored. Preliminary experience has shown that mesalazine or enteral nutrition may have a sign benefit in some cases.
Finally, we hope that the possible role of MMR will be elucidated and that further insights into the pathogenesis of regressive and classic autism will be provided.
Why should these children be investigated at the Royal Free Hospital?
The Department of Paediatric Gastroenterology and the Inflammatory Bowel Diseases Study Group are uniquely qualified to investigate this new syndrome. Not only has Professor Walker-Smith’s team (which transferred from the Medical School of St Bartholomew’s hospital on 1.9.95) a large experience in diagnostic paediatric colonoscopy, but also the range of tests required to investigate these children appropriately, and the basic scientific investigations required for analysis of tissues (including recognition of viral antigens) are all sited at the Royal Free Hospital. The molecular technology for detection of virus genetic material in blood, CSF and biopsy specimens has been optimised by molecular biologists in the Inflammatory Bowel Disease Study Group. In addition, investigations have been arranged with other workers both within the Royal Free and other institutions.”
Q Page 203A was put in at a later stage in these proceedings, do you see that?
Q Before we get on to that, this document, pages 200 and 203, again leaving out the dense detail of the science but where the elements addressing the question of what this study hoped to achieve, and the question why the children should be investigated at the Royal Free, were those issues that were addressed by you whenever you spoke to a GP or other medical professional, before this child was referred?
Q I say “this child”, a given child?
Q I think page 203A and 203B were put in at a later stage in the proceedings. I think you have a slightly different version that you are in a position to produce to the Panel?
Q Perhaps that could be done. (Same handed and marked as tab 14/D2). Dr Wakefield, can you now, taking this document D2/tab 14, indicate to the Panel where there is a difference between that document and the document which is currently before the Panel in the local hospital records?
A Yes indeed. This is the final version. You will see in the version that is in the local hospital records that is double or one and a half spacing, and that is often the way with drafts so that changes can be put in the spaces. This is single space this document and on the penultimate page there is the addition as to how referrals should be made to Professor John Walker-Smith and his department.
Q That is on the third page, and if you go back to the documents in the local hospital records it is self-evident, if you look at the bottom of page 203 and 203A, it does not follow on in the text, is that right?
Q And it does not have any reference to the person to whom the referral should be made.
Q Was this document, D2/tab14, in its completed form sent to doctors where appropriate?
Q I turn back now, please, to the Royal Free notes, just to look at a number of documents briefly. There is a letter from Dr Mills to Professor Walker-Smith, 12 May 1997, page 68. This letter was not copied to you. Is that right?
Q Can we now look, please, at page 66, a letter from Professor Walker-Smith to Dr Mills, copied to you, as you can see at the bottom of page 67.
“Many thanks for your letter. The successes that we have had with treating autistic children is an unexpected secondary aspect of our study, we had expected improvement with the gastrointestinal symptoms with use of 5 ASA derivatives and Salazopyrine, but we had not expected the parents to tell us there had been such an improvement in behaviour. We are in fact with the help of Dr Marc Berelowitz, planning a further study to analyse the successes …”.
Just pause there. As far as you understood it, what was that a reference to?
A This was a reference to the experimental study of 5-amino salicylates that I have been referring to.
“… but our work at the moment has been to provide a diagnostic service to determine the gastrointestinal manifestations of these children.”
As you understood it, was that an accurate assertion by Professor Walker-Smith?
A From his perspective, it is absolutely correct, yes.
“Dr Wakefield has written a paper with submission to the Lancet, which discusses the links between MMR and autism, it is under review at the moment and we are awaiting that decision.”
I take you to the date this letter was written – 29 May 1997. Dr Wakefield, can you help about that reference to a paper and The Lancet?
A Yes. This will be what ultimately came to be the published paper, The Lancet paper of the first twelve, which was clearly, therefore, under review at this stage.
Q What does that mean – “under review”?
A It means that the paper has been completed to the satisfaction of all the participating authors and that it has been submitted to the journal for consideration for publication.
“I am afraid it is not true that my department was energetic in requesting me to refer JS to you, the pressure is coming from his parents who have heard about the success with other children. My own position in this work is entirely responsive, when I transferred from Barts to the Royal Free I was quite sceptical about the research work of Dr Andy Wakefield…”.
Just pause there for a minute. Was that correct as you saw it?
“… but since I came here it is absolutely obvious to me that there is a large unmet need of children with autism who have a variety of gastrointestinal symptoms ranging from quite mild symptoms to quite major ones. The unexpected outcome of this research has led to us being very interested in the treatment of these drugs.”
This letter was copied to you. There is a reference there to “research”. How did you read that reference when your received this letter?
A I saw that as being a reference back to my previous work, about which he had expressed scepticism originally.
Q Then he says, and I think I should read it in fairness to Professor Walker-Smith, at the top of the next page:
“… I must again emphasise, that I am reacting to parent pressure, the other children who come from distant authorities, the referring authority has agreed to fund these children’s referral as an EC and the initiative must come from the general practitioner. I am myself not soliciting for patient to be referred to us, but I am reacting to the parents requests.”
Did you at any stage see it as Professor Walker-Smith soliciting patients?
A Not in the slightest, no.
Q Did you ever solicit patients?
Q That, as we can see, was 29 May and I want you now just to turn back a page to page 65. On 11 June 1997 there is a letter to you from Kirsten Limb at Dawbarns.
“Have you been able to fix up an appointment for JS to be tested? Things are getting worse regarding his stomach pains, ‘piles’ and peri-anal irritation and he now seems to be developing joint pains.
… (his mum) is very keen to bring JS to the Royal Free if you can manage it.”
Do you understand what that letter was addressing, and why it was that Kirsten Limb should be writing to you?
A Kirsten Limb was the scientific research assistant at Dawbarns. What this letter represents is a rather embarrassing situation for the medical profession. The mother has now sought to prevail upon Kirsten Limb, in a compassionate position, so it has nothing whatsoever to do with litigation, and is drawing my attention to the fact that this child’s symptoms continue to deteriorate and is of the hope or the opinion that an appointment might be forthcoming, and the mother may have asked her in this instance to try and intervene on behalf of her child, to encourage that appointment to take place.
Q Will you now turn to page 62. We see a letter from the mother directly to yourself on 5 July.
“Dear Dr Wakefield,
I am writing to ask if you could please refer my son, JS, for tests to see if there is any way he can be helped following the devastating damage caused by his MMR injection in 1992.”
And she sets out some of the current, relevant matters of his condition, which we can see.
“I would very much like to be referred to you as during my last appointment with doctors here it was made very clear that there is nothing they can do to help him medically bar seeing a psychiatrist for drugs and keeping him in an autistic unit.
I feel my doctors do not believe that JS has been damaged by the vaccination – in spite of the fact that he was a perfectly normal baby, and a bright, affectionate and highly verbal toddler. And in spite of the fact that the vaccine he was given was later withdrawn by the government because it carried a high risk of adverse side effects.
My husband and I feel we must explore every possibility to help our son. As it is now JS has no future at all – other than being sedated and confined in an institution.”
That letter, as a matter of fact, was copied to Dr Mills. The reference to that is at local hospital records, page 210. Were you in a position to refer JS in the light of that letter?
A I was not in a position to refer him at any stage. I was only in a position to act as a conduit for his mother’s concerns. In a previous communication to the Royal Free, I think Dr Mills had said that if there was a change in his condition, his symptoms, then he would reconsider. Here was clear evidence of a deterioration in his symptoms and I confess that I was somewhat perplexed as to why that had not caused him to change his mind.
Q At any rate, would you turn to page 63? Can I ask you this. Did you pass that letter from Mrs JS to you to Professor Walker-Smith?
A Yes, I did.
Q Professor Walker-Smith says:
“I am sorry that NHS funding is not available for JS to be seen by us.
If it is possible for you, I would be happy to see JS as a private outpatient in order to see if he were suitable for investigation and to discuss what is involved.”
It is copied to you. Following that, and I think we can take these fairly swiftly, was there an outpatient appointment – turn to page 2 – 30 July 1997. Again, do you recognise the writing there?
A That is Professor Walker-Smith’s writing.
Q Did you play any part in this outpatient appointment?
A No, I did not.
Q Following that outpatient appointment, you will find a letter at page 60 from Professor Walker-Smith to yourself. In the top left-hand corner, there is a reference to the clinic, 30 July, and a reference to “PP”, no doubt a reference to “private patient” – 30 July – and the letter is dated the 31st.
“You will recall that I have seen this child privately as Dr Mills wasn’t prepared for the child to be seen on the NHS. I have left it with the parents now to inform me whether they wish us to proceed for future investigation.”
Then I want you to look at this question.
“Is this one of the children that you may be able to have funds to cover the child’s admission on the NHS for investigation”
What did you understand that question to be directed to?
A This is a reference back to my allusion in previous correspondence to the possibility that Legal Aid Board funding might be used to cover the clinical investigations of this child.
Q Then, on page 58 and 59, just noting in passing, did Professor Walker-Smith then write to Dr Mills with a report of the outpatient appointment?
A Yes, he did.
Q There are in the notes examples of correspondence between the Royal Free, Professor Walker-Smith and Worcester Health Authority relating to the question of funding for a referral. Were you involved in any way with any of those to-ings and fro-ings and correspondence that I have just summarised?
Q Then, on page 8, towards the tail end of the pieces of correspondence, I just wan you to deal with this. On 10 November Professor Walker-Smith, in a letter copied to you, writes to the deputy contracts manager at the Royal Free.
“Dear Miss Lewis
I am very concerned to have your letter suggesting that JS cannot come for an admission on the 12th November. I think it is essential that this child does have a colonoscopy. This kind of service is just not available elsewhere for children with autism and for the special investigations which Dr Wakefield can offer.”
The rest of it is self-evident. It is copied to you. What do you understand the reference to be to “special investigations which Dr Wakefield can offer”? What does it refer to?
A These are the research investigations in my laboratory, using immuno-histochemistry for the detection of measles virus.
Q And as a matter of fact, we can complete the sequence. We can just see from page 17 of the Royal Free notes that this child was admitted between 12 and 14 November, and that should be “1997”. There appears to be a typo there. Did you have any role to play in the admission process of this child?
Q Did you have any part to play in the decision, or otherwise, to carry out various investigations?
Q Whilst we have the notes open, could I just take you, please, to page 43. What is that a reference to?
A This is a Royal Free Hampstead NHS Trust consent form for routine investigation, in this case colonoscopy, under general anaesthesia and biopsies.
Q Would you turn back to page 33? What is that document?
A This is a consent form for research biopsies pursuant of 162-95.
Q Did you carry out any research in relation to this child?
A Yes, I did. We undertook analysis of his biopsies.
Q That is all I ask you about Child JS. There are two short matters, two miscellaneous points I have. In relation to each of The Lancet children, and we have looked at eleven of them, do you accept as a matter of fact that each one of them was seen under the auspices of the NHS?
Q Either via ECRs or otherwise?
Q It may be that the Panel might find it helpful if you produced a short glossary of some of the terms that you have been referring to thus far. I think you have prepared such a document. Perhaps you could formally produce it now.
A Certainly. (Document marked tab 15 of D2).
Q Do you have a copy?
A I do.
Q As you will appreciate, this was prepared, by definition, before you gave your evidence, and the intention is that it should distil your evidence that you have given to the Panel in a helpful aide memoir for them, can you please just double-check that you are content with it and that it fairly reflects what you have been saying to the Panel about the use of these terms, from your standpoint?
A (After a pause for reading): Yes, I am happy with that.
MR COONAN: Thank you very much. Sir, that completes Dr Wakefield’s evidence in relation to the children and I am now going to start the topic of transfer factor which will take a little time.
THE CHAIRMAN: It would probably be appropriate in that case – I know it is slightly earlier than normal but then we can resume slightly earlier than normal as well after lunch.
MR COONAN: I am entirely in your hands.
THE CHAIRMAN: It is 35 past 12 so we will resume at 35 past one because it is better for us to assimilate the information and the evidence that we have received this morning and also that it will not break the continuity in your thought process that you will be going through this afternoon.
MR COONAN: Thank you very much.
THE CHAIRMAN: We will resume at 35 past one; Dr Wakefield you are still under oath and still in the middle of giving your evidence.
THE CHAIRMAN: Good afternoon. Mr Coonan.
MR COONAN: Sir, we are going to deal with the topic of transfer factor and, by way of introduction, could I just draw your attention to the heads of charge. You will see that 40(a) is live and head 41, but the topic also relates to head 38 but, more particularly, 39(a) (iii). We will deal with the specifics of 39(a)(iii) when we come to The Lancet itself, but in order to lay the ground I need to go through the topic of transfer factor as a whole.
Sir, for the purposes of the evidence there will be a need to look at a single reference in your bundle 1 and in the main we will be looking at volume 2 with a few references at volume 3, but they are much later on. Do you have volume 1 there, Dr Wakefield?
A I do, yes.
Q During the course of your evidence last week you touched briefly on the concept of a patent and how medical schools and so forth treated or dealt with the questions of patents. We will come in some detail to the question of a patent in 1997 but before that – and again it has been referred to in the course of the evidence so I want you to deal with it – was there a previous patent in 1995?
A Yes, there was.
Q Do we see a reference to that at page 127 in volume 1?
A That is correct.
Q The first main paragraph just deals with a certain amount of background and then in the third paragraph on the page there is a matter I would like to highlight and then ask you a couple of questions. It is a letter written to Brian Blatch, the secretary of the School, on 12 July 1996.
“In 1995, immediately prior to the publication of our article in the Lancet linking measles vaccine to inflammatory bowel disease …”
Is that the paper that you referred to earlier in the course of your evidence?
A It is.
“I read a paper showing that persistent measles infection in cultured cells could be treated with a novel molecular therapy … That weekend I sat down and wrote a patent, in order to try and protect the interests of all parties concerned, covering the diagnosis and treatment of inflammatory bowel disease using reagents and therapies directed against measles virus. You will appreciate that at this stage we have no conclusive evidence of causation and no specific therapy for treatment of patients with inflammatory bowel disease directed towards the measles virus. Nonetheless I thought it was worth putting in provisional cover since, on publication of our vaccine paper, it would then fall into the public domain and any chance of patenting it would be lost.”
Did that summarise the background and your motivation in taking out a patent in 1995?
A Yes, very much so. Once something is in the public domain then in patent law as I understand it, if it is evident to someone skilled in the art, then it is not patentable and therefore albeit that this was entirely speculative at this stage, I felt that it was worth at least submitting a provisional application.
Q Was this the first patent you had ever applied for?
A Yes, it was.
Q Before writing the patent, as you say in this paragraph, in order to try and protect the interests of all parties, did you either tell the medical school or seek its permission before lodging the application?
A No, I do not think I did.
Q Did you understand that you in fact required permission before doing this?
Q Had anybody ever told you about it?
Q After the patent had been registered was there a discussion with the medical school about it?
A Yes, there was. It was my understanding that we had received a directive to protect the interests of the medical school in matters like this where there may be intellectual property rights attached to any discovery or potential discovery, and that is what I was seeking to do here.
Q Was there any advice given to you following this 1995 patent about future applications?
A Yes, there was, the process by which a patent should be filed if any future patents were so filed.
Q Can you remember any particular element of that advice?
A There was to be a clear distinction between the discoverer or discoverers and the person who held the intellectual property rights, in this case the Royal Free Hospital School of Medicine.
Q Did you at that stage receive any specific advice from anyone that you needed to get permission first before seeking to lodge a patent to protect the interests, let us say, of the medical school.
Q That is all I ask you about the 1995 patent and we can put volume 1 away. Would you have to hand, please – we will not need it immediately – volume 2 of the Panel bundle.
Let us come to the question of transfer factor itself. To set the scene can I just place before you two uncontroversial matters: first of all, child 10, as we can see from our chronology of referrals, was admitted to the Royal Free on 16 February 1997 and was investigated on the 17th and, clearly, discharged shortly thereafter. I am not concerned with the precise date but it was round about that time.
Q With that as a piece of background information can you tell the Panel, first of all, whether there came a time when you became aware of the existence of this substance called transfer factor?
A Yes, there was. I had attended a conference in the United Stated and I had met with Professor Hugh Fudenberg who was introduced to me as an eminent immunologist who had a specific interest in autism and who was an expert in the field of transfer factor.
Q Can you tell the Panel approximately when this was?
A It will have been some time in 1996 I think.
Q As a result of meeting with Professor Fudenberg what did you learn about transfer factor?
A I learnt that transfer factor was a potential if somewhat poorly characterised immune therapy. Transfer factor is reported and has been reported in the scientific literature to be able to confer upon someone who is not immune to a specific agent such as measles virus, for example, immunity to that virus, so without actually having been exposed to the measles virus the transfer factor taken from someone who has been exposed to measles virus, that immunity can then be transferred to the recipient such that when they are exposed to the virus and infected with it they are able to handle that virus and clear the infection without severe adverse consequence.
Q Is that what you learnt from Professor Fudenberg at that early stage?
Q Did you see either then or at some time after then a potential for the exploitation of that substance?
A Yes, I did. If it was the case that these children had become persistently, that is chronically, or in the long term infected with measles virus because their immune system was unable to clear it, there was the possibility that transfer factor, a measles virus specific transfer factor, might be able to help their immune system or educate their immune system appropriately to clear that virus.
Q Did you do any reading around the subject following that discussion or discussions with Professor Fudenberg?
A Yes, I did. I found the concept fascinating. I was slightly sceptical but I obtained all of the literature that I could get my hands on and read around the subject. Some of the literature was better than others but it was nonetheless, clearly in the minds of many scientists, including immunologists, a real and potentially valid concept.
Q Did you consider who might benefit from exploiting the potential use of this substance?
A Yes, those individuals who, for one reason or another, some abnormality of their immune system’s response to the infection, were unable to clear the virus without this specific agent boosting their immune system to enable them to do so.
Q Did you consider therefore the question of exploitation via a patent?
A Yes, I did.
Q We will go straightaway to that. If you look in volume 2 and start, please, by turning up page 474. I am going to read this letter, it is addressed to Ruth Bishop: what was her position?
A I believe that Ruth Bishop was part of the medical school’s initiative to create a commercial enterprise, a way of dealing with potentially valuable and exploitable discoveries made by members of the school.
“Please find enclosed copy of a further patent that we have filed regarding the issue of measles and Crohn’s disease.”
Pausing there, in relation to the filing of this document did you get formal permission before you did it?
A The measles virus and Crohn’s disease one?
Q Yes, “a further patent that we have filed regarding the issue of measles and Crohn’s disease.” This is 1997 and it is a reference to the patent which follows.
A Did I get permission? No.
Q Did you understand you needed to get permission?
Q You then go on:
“It appears that we may now have a treatment for this condition based upon a substance called Transfer Factor which, although it has been around for a long time in other forms, can now be made specifically for measles virus. I felt that in view of the potential of this therapeutic and the imminent disclosure of data we should cover this application since it was not adequately covered in the first patent. The patent, as you will see, is filed in the School’s name and that of NIT Research Foundation who produce the Transfer Factor and with whom we are collaborating on our clinical trial. The School may wish to fund this at this time. In the meantime I will cover the cost with Roy Pounder. I do feel, however, that this is a potentially valuable strategy and gets us away from the anxieties expressed by the Dean over diagnostics and litigation, although a diagnostic kit is still a desired goal of our research.”
Can you summarise for us, therefore, the background to that letter and we will look at the patent in a minute?
A Yes, in the filing of this patent what I am doing is acting on the prior instructions of the medical school to dissociate the inventors from the owners, the patent was rightly, in my opinion, jointly filed in the school’s name and that of Professor Fudenberg’s research foundation, since they had done a great deal of the work in relation to transfer factor and funding from the school had been somewhat difficult to come by but I was personally willing to meet the initial costs of these patents, albeit that the medical school would be the beneficiary because I felt that it was at least professionally a worthwhile approach.
Q If you turn the page to 475, that is a letter from Ablett and Stebbing to you, and just help us, we had some evidence about Ablett and Stebbing but can we have it from you, please?
A Yes, Ablett and Stebbing are a chartered patent attorney company on Baker Street, and Peter Stebbing was the patent attorney with whom I had specific dealings.
Q For those who may not know as much as others about it, what do patent attorneys do?
A Essentially, they take the evidence that you present to them and they distil it into a specific document, which seeks to protect your intellectual property in that matter.
Q On page 475 we see the applicant, Royal Free Hospital School of Medicine and Neuroimmuno Therapeutics Research Foundation, is that Professor Fudenberg’s research foundation?
A It is.
Q On page 477 there is the invoice I think in respect of registration and preparing the application: did you pay that?
A I did.
Q Page 479 is the formal filing receipt of the patent, dated 6 June 1997, and again the applicants are identified. Then we come to the body of the patent itself. This document is a document which deals with the claims in respect of transfer factor. Is that a term which is used in patent law?
A That is correct, yes.
Q What is it? It may have different meanings in different parts of the law but what does it mean as you understand it in this area?
A A claim is that specific element of the patent that defines what it is you are seeking to protect from infringement, from, for example, competitors.
Q Who drafted the document which we see at page 480, running through to page 491?
A Peter Stebbing.
Q Did he have any written material upon which to base this document?
A Yes, he did, he had a scientific overview from me.
Q I am not going to slavishly follow the wording of this document but I want you, please – and it is an important matter – to summarise the two major claims set out in this document at 480 and 481 in particular.
A The patent seeks to claim for the use of transfer factor in two ways. Firstly, as a therapeutic agent for the elimination of measles virus from the tissues from the body of patients, individuals infected with measles virus, that is people who have got an established infection and associated with that established infection a chronic disease and for some reason by virtue of a deficiency in their immune system are unable to clear the virus. The second claim is for transfer factor in the role of a prophylaxis or vaccine, and that needs to be clarified in some detail because it has been the source of confusion. Particularly it has been the source of confusion with respect to its possible role as a competitor to MMR and that is not the case, and the reason is that the success of live viral vaccines such as MMR, such as measles, such as the mumps, such as rubella, such as the chicken pox vaccine, rely on the fact that they are able to induce an antibody response, that is they are able to induce in the host immune system the production of circulating proteins or proteins that are present at the surface lining of the body, such as the intestinal tract or lungs, that upon encounter with the virus neutralise it immediately. In other words, the patient does not become infected, and the consequence of that is that it breaks the chain of transmission of that virus from an infected individual, or one who has been exposed, to a naïve or unexposed individual who has not previously seen measles, and that is the basis of the success of live viral vaccines.
In contrast, transfer factor does not do that. It does not induce antibodies. Specifically, what transfer factor does, and I think Professor Lachmann has referred to this, he said it induces that arm of the immune system that is known as the cellular immune response, and the role of that aspect of the immune system is to target infected cells in individuals who already have got the infection: in other words they have been exposed; the virus has got into the body; has infected cells and then that provokes the cellular part of the immune system to clear the virus. So in contrast with live viral vaccines, transfer factor as a vaccine could not break chains of transmission and therefore at the population level it could not be a successful vaccine. However, there are a group of individuals, a small number of children and other individuals, who by virtue of defects in their immune system, either genetically based or acquired, such as in patients infected with HIV, who cannot mount a response against viruses and in those individuals a live viral vaccine is contraindicated, it is specifically contraindicated, and this can be found upon the product insert for the vaccines themselves. Why? Because if they are given a live viral vaccine and their immune system is incompetent then that viral vaccine can replicate within the body and cause severe adverse consequences and possibly death. So, in that group of patients, that group of individuals in whom the vaccine, the live viral vaccine is specifically contraindicated, transfer factor may have a role. The reason for articulating this argument, and the reason for making, filing this claim is based upon a paper that was published in the New England Journal of Medicine by Steele et al, and at some stage that may be introduced, but just to give you the background: it has been said during the course of these proceedings, I think by Professor Zuckerman and by Professor Lachmann that there really have not been many good studies (if any) of transfer factor. In fact there have, and this was one such paper, published in the New England Journal of Medicine, which as I am sure you are aware is a pre-eminent journal, this was a randomised control clinical trial of children in remission from lympoblastic leukaemia who are very susceptible to chicken pox and adverse reactions to chicken pox, including encephalitis and death, and the reason for that … Sorry Mr Chairman.
THE CHAIRMAN: I was just going to ask Mr Coonan: I do not mind listening to all these things but I just wonder whether they are in any way related to the ---
MR COONAN: I was letting it run just for a moment, after a purpose, but I take your point.
MS SMITH: May I intervene to say I too was just letting it run for a moment but since an interruption has in any event occurred, sir, as a result of your question, I think I am right in saying – and I am sure that someone will very quickly put me right if I am wrong – that these papers were not put to any of my experts, and in those circumstances, and in view of the fact that Dr Wakefield’s role here is not as an expert, it seems to me to be inappropriate that he should be allowed to venture into them in any event.
MR COONAN: I entirely accept that the Steele paper was not dealt with, I entirely accept that, and I shall clarify this with Dr Wakefield. It is the purpose of the underlying basis for the application is what I am concerned about; what was in fact available to him at the time he wrote the paper, in terms of learning. I am not seeking to put him forward as an expert on transfer factor, at all. Since we now have had the intervention perhaps I can go back and take your point.
(To the witness) Dr Wakefield, it may be that I was at fault in allowing your enthusiasm to run away, but can we get back to the essential point, which was to establish what your knowledge base was and understanding was at the time the application was filed. Do you see there is a distinction, or may be a distinction, between that and an overall post facto assessment of the rights and wrongs, good or bad, claims for transfer factor and it is the latter point I am not concerned with.
In terms of your knowledge base and understanding at the time the application was filed, was that knowledge base gained from Professor Fudenberg and from reading around the subject?
A Yes, it was. I apologise if I have misunderstood. I was trying to define that knowledge base and the reason for the inclusion of those elements.
Q So everybody understands, I am not in any way resiling from the position we took in relation to Professor Lachmann at all, was the Steele paper one of the documents or papers that you read at the time?
A Absolutely, it is included in the patent.
Q So, has everything you have said thus far, so we are absolutely clear about this, did that inform you when you put together documents for the assistance of Peter Stebbing?
Q Is there any other piece of learning that was available to you at the time which informed the support for one or other of the two claims which are made in this patent?
A I relied entirely on, on the one hand, our observations on these children at the Royal Free, and on the other hand on the published, the peer reviewed and published literature in relation to transfer factor.
Q As we know from these documents, that patent was filed – we have seen it already – on 6 June 1997. The next matter, please, for consideration in terms of chronology is a document which is not in the bundle yet, and I am going to ask that it be produced to go in as pages 494A and following. We have already paginated the bottom of it. (Same handed) Dr Wakefield, this is a letter dated 23 July 1997, and in fact it is addressed to Wendy Spicer, the Dispensary Manager, and it is written by you, if you see that at page 494B, both by you and by Professor Walker-Smith.
MR COONAN: Both of you have signed the document. I can say that this document has been supplied to us by Professor Walker-Smith’s legal team, is that right?
THE LEGAL ASSESSOR: Mr Coonan, just so there is no doubt later, can you explain now why it is – you have told us to whom this is addressed – on the copies we have the addressee is blanked out.
MR COONAN: It came, in effect, from Professor Walker-Smith’s legal team ---
THE LEGAL ASSESSOR: It came in this condition to you?
MR COONAN: In this condition as well. In a minute another document will be disclosed where the name is not redacted. Quite why they did it I have no doubt Mr Miller may be able to explain in due course, but that is the condition in which we got it.
THE CHAIRMAN: Mr Miller is happy to explain it now I think.
MR MILLER: I am happy to explain now: this document came to us as well in this redacted form and was provided by the Royal Free during the course of the proceedings, but it came with the name blanked out. We were aware that there was documentation at the Royal Free, asked for it and the Royal Free’s solicitors sent this document with the name of the recipient of the letter blanked out.
THE LEGAL ASSESSOR: So we can show a slight degree of respect to the rules of evidence, can we take it that it is an admitted fact that it is to the person to whom Mr Coonan says it was addressed?
MR MILLER: Yes, I think the next document will indicate that it was.
THE LEGAL ASSESSOR: Thank you.
MR COONAN: I think I should also say that we received this I think a couple of days before this hearing reconvened in March of this year.
MS SMITH: Perhaps I can also say when we got it as well, when Mr Coonan and Mr Miller shared it with me about three days ago.
MR COONAN: (To the witness) Let us look at the letter signed by you, 23 July 1997:
“We are currently involved in the investigation of a syndrome in children comprising regressive behavioural disorder (autism, chronic non-specific colitis and ileal lymphoid nodular hyperplasia). This complex syndrome appears to have arisen in many children following exposure to either measles or the MMR vaccine, and we have recently obtained conclusive evidence for the persistence of measles virus in the intestines of these children.
We have, over the last year, been dealing with Professor Hugh Fudenberg, lately Professor of Immunology at the University of California (IRVINE), who, as one of the world’s leading immunologists, has been involved in the production of an anti-viral therapy that may be appropriate for use in these children. The therapy – Transfer Factor – derives from the dialysed lysates of lymphocytes exposed to the appropriate antigen. Thus Transfer Factors can be made that are specific for any virus. Their affect appears to confer specific reactivity upon the host immune system to the particular virus in question, and therefore help the body to eliminate it itself. There have been more than 300 peer-reviewed scientific publications on the use of transfer factor and its effects over the last 30 years, and it has been dispensed widely without ever producing any adverse effects. I enclose a bibliography of some of the relevant references to Transfer Factor.”
Pausing there, is that attached at 494c-e?
Q And are those Medline extracts?
A Yes, they are.
Q And had you read those references as part of your reading process that you described earlier?
A I had read the full papers, yes.
Q I continued:
“We have been approached by the mother of one of our patients, [Child 10], who is desperate to try this new treatment for her child. We managed him initially with Salazopyrine in order to get his intestinal symptoms under control, and to some extent this has worked. However, he has subsequently regressed again and is now completely uncommunicative. Although we do not know whether the treatment will work, we are aware that Professor Fudenberg has treated two such children in the States with measles-specific Transfer Factor. One child who was previously rated very poorly on the autism scale, has just entered into first grade school. The second child has just commenced on the treatment.
After due consideration, we would like to start the child, [Child 10], on measles-specific Transfer Factor, and we are prepared to take full responsibility for the outcome of this treatment.
The supplies of the drug are presently in our hands (Dr Wakefield) and will be deposited with Pharmacy later this week when he returns from Birmingham. We look forward to hearing from you at your earliest convenience.”
Then, on the rest of the letter, on page 494b, there are a series of handwritten observations. I will come back to them. First of all, are they in your writing?
A No, they are not.
Q The letter can we just put to one side, please? I shall come back to it, but I want to ask you a number of background questions. Why did you write to Ms Spicer in the first place?
A As I said, as has been said in this letter, Mrs 10 was aware we had an interest in transfer factor and indeed was aware that I obtained some transfer factor. The reason for obtaining it was another matter which I am sure you will want to discuss at the appropriate time. Nonetheless, she called me saying that her child had regressed. She was extremely tearful. He had become completely uncommunicative and she asked if we would allow him to go on transfer factor, the measles-specific transfer factor. This was clearly not my decision. I had done a lot of the background reading, specifically in relation to the efficacy and the safety of transfer factors and with that information, and with the impassioned request from Mrs 10, I consulted with Professor Walker-Smith.
Q Was there any view, either on your part or Professor Walker-Smith’s part, that you would need permission to give this?
A Yes, there was. This was not a clinical trial. This is what is known as a “named patient basis” and this was, as Professor Walker-Smith pointed out to me, appropriately put before the Medical Advisory Committee and that is what we endeavoured to do.
Q Just tell us how it works. A “named patient bundle” basis: is this an application for permission to do that?
A That is correct.
Q And what did you understand would be the procedural route by which this would be considered?
A This is not something that requires ethical committee approval but it does require that the Medical Advisory Committee is informed, and their permission is sought, and that everything else is done in accordance with the recommendations from the Medical Advisory Committee.
Q What was Professor Walker-Smith’s reaction when you consulted him?
A He wanted to be reassured about safety, and he sought some background information on the efficacy of this product. It is, just by way of background information, not a drug. It is an “over the counter” product, classed by the Food and Drug Administration of America as a nutritional supplement and freely available . You can purchase it on the internet, or from clinics such as Dr Fudenberg’s so it is a nutritional supplement. It is not classed as a drug. Nonetheless, I had done a thorough background review of the safety, and I was able to reassure Professor Walker-Smith on that.
Q By definition you would have these discussions with Professor Walker-Smith before 23 July 1997, as we can see from this letter?
Q As far as you could judge, and as far as you could judge from Professor Walker-Smith’s reaction, if there was permission forthcoming for transfer factor to be given, were there any other concerns, any negative views that should be expressed before this was given on a named patient basis?
A I think the key is “fully informed parental consent”, to this extent. Dr 10 was fully aware of the background to transfer factor and had, for other reasons we may come to, came to know a great deal about the subject. He is by training a XXX and had a specific interest in this area. He was, as a parent, highly sophisticated in the background to transfer factor. That was an important consideration, so the parents were fully informed to an extraordinary degree and had made this request themselves. Those were important factors in determining, I think, the decision that was made.
Q We will deal with what flowed later. One other background factor is the obtaining of transfer factor itself. I think you told the Panel that you had obtained some?
A That is correct.
Q Where did you obtain it and in what circumstances?
A This was given to me by Dr Fudenberg and it was given to me whilst I was at a meeting in America. This was transfer factor that he would otherwise have given to patients, prescribed in his clinic. The reason for obtaining it in the first instance was to try, using biochemical methods or chemical methods, to purify the transfer factor, to find out which part of it was the active ingredient, if any. In other words, the way in which it was produced and had been used as a nutritional supplement meant that it was a sort of pot-pourri of molecules. Some or one of those may have had specificity as an anti-measles virus transfer factor. By the technique of electrospray mass spectrometry it was my intention to have this transfer factor analysed to see if we could purify the active ingredient, identify its chemical nature and thereby purify it and study it in greater detail.
Q When you wrote the letter to Wendy Spicer, was there any evidence available to you from your researches to suggest any adverse outcome, or the possibility of adverse outcomes, if this were to be given to a patient?
A transfer factor can be administered in a variety of forms. The form that we were proposed was as an oral preparation. As an oral preparation, from my reading, I had not been able to identify any adverse outcomes.
Q Did you address the question of safety when you were dealing with the patent application towards the end of May, beginning of June?
A Yes, I did. One of the elements that I was concerned to research and communicate in that patent was a review of the safety issues.
Q If you look at page 485, page 6 of the patent, and pick up line 19, is that a relevant observation in the context of the question I was asking you?
A Yes. That paragraph is a distillation of that, yes.
Q Before we take the next step, stand back again. Why was Child 10 potentially suitable for having transfer factor?
A Apart from the parental request and from the sophisticated knowledge of the family of this potential therapy, there were two elements of this child’s condition which made him particularly suitable. One was the fact that at that stage in my laboratory we had identified measles virus protein in his biopsies and the second, as you have seen in his clinical record, was this extremely high measles antibody level. It was at a level that is similar, in fact in excess of, that seen in children with the rare fatal encephalitis, subacute sclerosing panencephalitis, present at a very worrying level. What this suggests, as I have said before, is a vigorous, ongoing immune response to measles virus. So those elements made him particularly suitable for the receipt of this possible therapy.
Q There is at about this time a reference in the general practitioner notes which may be helpful just to look at briefly for Child 10 at page 65. You will see the letter is dated 7 August 1997 and is from Dr Paul Davis, the consultant community paediatrician, to Dr Thomas, the GP at the time. The body of the letter I am not concerned with, save for the observation at the end of the first paragraph:
“He is on Salazopyrin for bowel inflammation and is awaiting some new treatment with measles transfer factor.”
Would that accord with your understanding of the events as they were being processed at that time?
A Yes, it would.
Q I am going to ask you to look at the second letter which I indicated you would be producing.
THE CHAIRMAN: The number is paginated at the bottom, 607a, so I take it that it goes into this bundle and that would be the appropriate place?
MR COONAN: That is right. (To the witness) This letter is dated 15 September 1997 from Dr Geoffrey Lloyd, the Chairman of the Medical Advisory Committee. It is to you, “Dear Andrew”. The subject is “Measles virus-specific transfer factor”.
“Thank you for your letter of 9 September 1997…”
which we do not have –
“and for the copy of your joint letter with Professor Walker-Smith to Wendy Spicer dated 23 July 1997.
I am prepared to give you Chairman’s Approval for the use of transfer factor for the patient you referred to in your letter of 23 July, namely, [Child 10]. This should be used on ‘a named patient basis’. I will be very interested to learn of the outcome of treatment in this case, but I cannot give you permission to use the drug more widely. I note that you intend to conduct any open study of this therapy; you should seek approval from the Ethical Practices Committee before you embark on the study. If ethical approval is granted, then the drug will be made available to you by the Pharmacy.”
By this stage, had you in fact made the transfer factor available to the pharmacy as you had indicated at the end of your letter we looked at earlier?
A Yes. I think my agreement was when I returned from Birmingham to put it into the hands of the pharmacy.
Q So having got this letter from Dr Lloyd, as you understood it, what did it permit you to do?
A From this point forward it permitted Professor Walker-Smith to problem this treatment, or this possible treatment, for Child 10.
Q Was that subject to satisfying firstly yourself and, as you understood it, Professor Walker-Smith of the safety of the product?
A Yes, indeed.
Q What about the assessment of safety of the product at this stage? You had the permission to give it on a named patient basis, what other steps, if any, needed to be taken?
A Specifically in the context of the child to whom it was administered it was important to monitor that child closely by remaining in contact with the parents so that should any adverse reactions, any adverse events at all, arise we were aware of that. In addition, at least to that end, to make sure that his gastrointestinal symptoms did not deteriorate and indeed may show some improvement, we instituted a system of pro forma questionnaires that the mother or the father would complete and then return on a regular basis to the clinical research nurse, Jill Thomas.
Q Apart from discussing the matter with Professor Fudenberg and considering the literature which was in play at the time, were there any other steps that needed to be done to satisfy both yourself and Professor Walker-Smith – we can ask him of course what his state of mind was – about the safety aspects of this product?
A The product was given in a labelled form to pharmacies so that they could appraise it and check that they were happy with the safety aspects from their particular point of view.
Q Did you do any further reading?
A Yes, during the course of that time there was a conference on transfer factors and I obtained the proceedings of that conference and read it and continued to read around the subject.
Q Were you considering at about this time the setting up of a study?
A Yes, we were as referred to in this letter, in Dr Lloyd’s letter, we were anticipating an open-label clinical trial. The purpose of an open-label clinical trial is first and foremost to assess safety. Assessing efficacy – that is the possible clinical benefit – is a secondary consideration, so safety and efficacy were to be considered and that was to be a formal application put through the ethical practices committee for a trial of transfer factor in these children.
Q I am going to ask you to produce a draft of the study, please, for a particular purpose. It is a lengthy document but fortunately there are only three references that I need to take you to. This will be tab 16. (Document distributed). Dr Wakefield, do not worry for the moment about the first page, can we just look at the second page of this. Is that the title on page 2 of the proposed clinical research study?
A Yes, it is.
Q If you turn to page 22, is there a section there that deals with matters relating to safety?
A Yes, there is.
Q Can you just point it out to us?
A It is the section entitled “Adverse events associated with use of DLE-TF” – that stands for dialyzable lymphocyte extract transfer factor.
Q As you assert there, “DLE-TF is virtually free from adverse side effects (reviewed by Fudenberg and Pizza).” Did you read that?
A Yes, I did.
Q In relation to this document, I do not know if you can say, but if you look at page 27 is there anything else there that relates to the issue of safety in a general matter?
A Yes, I have quoted or abstracted from certain seminal papers that had a major influence on our thinking in this area and summarised any adverse events that had arisen during the course of those clinical trials.
Q Then on page 30 there appears to be a bibliography relating to transfer factor, is that right?
Q There are a considerable number of these, had you read all of these?
A I obtained and read all of these papers, yes.
Q As papers as opposed to extracts?
A The full papers, yes.
Q As matters stood when you did that exercise, what was your attitude to the safety in relation to transfer factor of giving it to a child patient on a named patient basis?
A In my opinion it had a very acceptable safety profile.
Q We now turn to the first page of the document and we see the title which is, on the photocopy, partly obscured by a computer screen print. I will leave you to explain, please, what we are seeing there and what is the significance that the Panel should derive from that photocopy.
A I am sure many Panel members will be aware that in Word documents you can go to a properties page in order to look at the size of the document, when it was produced, when it was modified and when it was last printed, and in order to reassure the Panel that this document was prepared and printed at a particular point in time, that is what we have done here. The document, if you go to the first line, says “Created” and gives a date in 2007. That is because it was transferred from one computer to another at that point and that was not the date on which it was created. If you look at the fourth entry, when this document was printed, you will see it was 7 November 1997, so this document was available in this form and printed in November 1997.
MR COONAN: Sir, I am going to go on to the actual administration of transfer factor; you may consider this to be an appropriate moment to take a break.
THE CHAIRMAN: Yes, indeed. It is ten to three so we will now have our short break.
MS SMITH: Now Mr Coonan has come to a natural break I wonder whether I might raise one matter very quickly with you, because it would be helpful to me to do so before the break. It relates to the documents that have been produced very lately, in particular to the page that has been put in at page 607A of the bundle, the letter to Dr Wakefield from Dr Lloyd. Sir, you will notice – and Mr Coonan has already pointed this out – that that starts off “Thank you for your letter of 9 September 1997 …” and it would seem to be a natural construction that the letter of 9 September 1997 gave the information to Dr Lloyd on which he bases his apparent permission. It seems to the General Medical Council that the letter of 9 September 1997, in other words the information that was given to Dr Lloyd, would be a very important document for the Panel to have when they are considering this issue. We have already instituted enquiries, but as you will appreciate, sir, this is a long time ago, the Royal Free is a very large place and there are huge numbers of documents all over the place. We are doing the best we can but it occurs to me that the Panel may feel that it is appropriate that they should say that they would wish to see this document as soon as possible and that would assist those instructing me in their attempts to trace it.
THE CHAIRMAN: I am looking at the Legal Assessor to make sure that he agrees with me because I do think that this document of 9 September might actually be quite a helpful document, putting the whole thing into the proper context.
THE LEGAL ASSESSOR: Of course, this Committee, operating under the Old Rules, can call for the production of such a document.
THE CHAIRMAN: If such a document can be found then I am sure that the Panel would find it very helpful. Mr Coonan, have you any observations on this?
MR COONAN: Only to say that that is an excellent idea; if we had the document we would produce it, but we do not. Ms Smith has referred of course to the passage of time and I will have something to say about that later as it is not entirely irrelevant. I should also say that the letter at 607A that Ms Smith has just referred to, this letter did not come from Dr Wakefield either, this was provided by Professor Walker-Smith’s legal team. We have no documents to produce.
THE CHAIRMAN: As I understand it from Ms Smith’s contribution, she is also going to ask her legal team to try to find this particular document if that is possible.
MR COONAN: Yes, and I support that.
MS SMITH: It is the Panel’s support that I was really seeking and, as Mr Seed has said to you, you may ask – and it may be worth bearing this in mind during the course of this hearing – for any document which, in the public interest, you think you should see. It seems to me that this comes into that category and I would like to be able to tell the Royal Free that you said so.
THE CHAIRMAN: I am quite sure the Panel would wholeheartedly support this, that if you can get your hands on this document the Panel would really like to have a copy of this document.
MS SMITH: Thank you, sir. As I said, it is not my hands.
THE CHAIRMAN: I appreciate that. In that case, this is the right time to have a short break, it is five to three and we will resume at quarter past three. Once again, Dr Wakefield, you are still under oath.
MR COONAN: Dr Wakefield, we had reached the point at which you had got a letter giving permission from Dr Lloyd, you had carried out your researches on the literature and you had formed a view about safety. We had reached in chronological terms November 1997. I want now to turn to the administration of transfer factor to this child. Did you and Professor Walker-Smith have any further conversations following the receipt of the letter from Dr Lloyd about the giving of transfer factor to this child?
A Yes, I am sure we did. I cannot remember the precise details but undoubtedly we will have done.
Q Do you accept that transfer factor was in fact given to the child?
A Yes, as far as I am aware it was.
Q In your own words, please, can you explain the circumstances in which that came about?
A The decision by Dr Lloyd, the approval by Dr Lloyd, will have been communicated to the parents and from that point onwards I will have given the compound to the pharmacist at this stage, with a copy of the protocol or at least part of the protocol describing those elements of dose, for example, and conditions for storage of transfer factor.
Q What did you understand occurred then?
A What would happen is that it would be administered, given, from the hospital pharmacy.
Q Where it was residing.
A Absolutely, yes.
Q Was there any discussion as to how it was going to be effected, having got this general permission, who was going to effect it and so on?
A I think on that point it would have been down to Professor Walker-Smith or his secretary to arrange an appointment for Mr and Mrs 10 to come to the Royal Free and for the drug to be prescribed.
Q In the light of the specific charge at head 40(a) I must ask you this, did you administer the transfer factor to this child?
A No, I did not.
Q I want to ask you about the dates that the Panel may have to consider: you have told us about the date on the computer printout. It might be helpful to turn up the Royal Free notes for child 10, page 181. First of all, have you seen this document before as a document?
A Yes, I have.
Q If you go back two or three pages you will see a checklist: what do you understand this document to be in principle?
A This is a proforma for the aberrant behaviour checklist. This is a scoring system to be filled in on this occasion by the parents denoting the severity of various behavioural problems in a child with a developmental disorder such as autism.
Q We have towards the bottom of page 181 an entry to which attention was directed earlier in the proceedings, six lines from the bottom:
“ …but he is not as good as he has been recently. Over Christmas and New Year we felt very optimistic about the apparent effect of transfer factor. There seemed to be such a noticeable change in [child 10] but this week we feel pessimistic. This may be a stupid question but is it possible that the dose now needs to be increased?”
Did you come to have an understanding that this child had had transfer factor?
Q When did you understand that he had had transfer factor?
A I do not know the precise date but, clearly, over the period that these report forms were filled in.
Q How do you know that Mr & Mrs 10 gave fully informed consent to the administration of transfer factor?
A As I said, Mr 10 – or Dr 10 – was highly sophisticated in this field, holding a PhD in XXX and he had been in contact with both Dr Fudenberg and Professor Charles Kirkpatrick of the University of Colorado, who is one of the world’s authorities on transfer factor, and had spoken to him at length. He had read the literature and XXX.
Q Did you have any responsibility to inform the GP that this child had had transfer factor?
Q Did you have any responsibility or obligation to make any entry in the clinical notes at the hospital that this child had had transfer factor?
Q Let us look at how this has been described, and you will need to look at FTP2, page 675. We will go back and look at this document but for another reason in a moment. The document is dated 2 February 1998, a letter written by yourself to Dr Pegg:
“Please find enclosed 18 copies of our trial …”
And you set out the title of it:
“We would like this to be considered by your committee at the earliest possible opportunity.”
Again, I will come back to that later but it is this part I am interested in:
“One child who has received this treatment on a compassionate basis appears to have made substantial improvement without any noticeable adverse effects.”
What did that phrase intend to convey when you wrote it, Dr Wakefield, “treatment on a compassionate basis”?
A This is a reference clearly to child 10; it refers to the compassionate basis on which the drug was given with approval, that is based upon the mother’s request to me initially for this to be given to her son and it was my impression at that time, based upon the mother’s reports, that he had shown substantial improvement. Sadly, those were not to be sustained.
Q If you then go to page 680 in the same bundle, halfway down:
“Virus specific transfer factor has been given in millions of doses without adverse effects, other than mild pyrexia in rare instances.”
“Anecdotally, we have started one child with autistic enteropathy on DLE-TF on an approved compassionate basis; he has tolerated the therapy, for one month so far, without any adverse effects and according to his parents has shown definite improvement.”
It is the phrase there “approved compassionate basis”, what did you mean by that?
A “Compassionate” refers, as I said before, to the mother’s request and the “approved” refers to Dr Lloyd’s approval as the chairman of the Medical Advisory Committee.
THE CHAIRMAN: (Interruption from the public gallery) Mr Coonan, would you wait for a second? I am concerned because I think it will distract Dr Wakefield’s concentration as well.
THE LEGAL ASSESSOR: Perhaps the legal representatives will consider before tomorrow about what advice I should give about any interruptions like that.
MR COONAN: Yes, thank you.
THE CHAIRMAN: (After the man and boy left the room) Mr Coonan, would you continue for the time being?
MR COONAN: (To the witness) Dr Wakefield, I want to run through with you some background matters relating, first of all, to the existence of the two studies that are in these documents for you to comment as we go through it. Some of this, I anticipate, may not be controversial but I want to try, with your assistance, to make sense of the documents in the bundle to help the Panel, all right?
Q The first is at page 506. It is dated 8 August 1997 and is from Mr Tarhan to Professor Revell. I am just going to read the first paragraph:
“You may be aware that Andy Wakefield has put forward a proposal to Freemedic to fund his research work which we understand may identify a treatment (not cure) for Crohn’s disease. The procedure has been patented. The problem I have is understanding the science involved.”
Dr Wakefield, the study involved is I think attached to that, running from pages 507-605, can you confirm that?
A That is correct.
Q You will be relieved to know that I shall not be delving into this. I want you, please, just to be able to identify it, label it and tell the Panel what it was about.
A This was a proposed clinical trial of measles virus specific transfer factor not in children with autism but in Crohn’s disease ---
Q Has it got anything to do with autism?
A No, nothing at all.
Q Sorry, I interrupted you. Is there anything else you want to add about that?
Q The Dean responded to that, I think, at page 607, so a funding issue. What was the response of the Dean, just as a matter of fact, please?
A He declined the application.
Q Then we move on to page 620a. It is Mr Tarhan to you. I just draw your attention to the first paragraph. Also, look at the first few lines of the second paragraph. Perhaps you would just care to read it through to yourself, please. (The witness did so)
Q In terms of funding what was the watermark for the position in relation to the study you have spoken about?
A There was no funding to be forthcoming from the medical school, and I had been told to go and find it independently, either from the pharmaceutical industry or from venture capital.
Q And what of the reference in the middle of the second paragraph to “…covering 50% of the costs through central School funds…”?
A I think that Professor Pounder and I, and myself in particular, had been bearing the costs of all of these patents personally, albeit that the school were to be the beneficiaries if they were successful. There was a small amount that would derive to the inventors, but our intention (that is Professor Pounder and I) was to use those to build a new centre for gastroenterology at the Royal Free. So the school, effectively, would have been the beneficiary in total. Nonetheless, we still had to continue to pay fifty per cent of the balance.
Q On page 627 this is a draft letter from Nicola Baker-Munton of the intellectual property department. Is she at the Royal Free?
A I think she acted at least in part at the Royal Free but not exclusively.
Q I am not concerned particularly with the fact that it is a draft or whether it was in fact sent because at the first sentence it says:
“Dear Dr Wakefield
Thank you for an informative meeting on 11th November 1997 and the copies of the paper and first patent filing which I received this morning.
First, I should confirm that it will be very difficult to excite a pharmaceutical company based on the current intellectual property position of the Transfer Factor. I believe you agreed with this and acknowledge that further work needs to be carried out to try to characterise the active component(s).”
As matters stood in November 1997, Dr Wakefield, what was the general position in relation to the study that we have looked at and the question of funding?
A There was no funding, and it was held in abeyance.
Q Then we move on to February 1998. Can we move to page 675, a document we looked at about half an hour ago. What is the nature of this study or trial?
A This is a study, a proposed open-label study, of transfer factor in the treatment of children with autistic enteropathy or autistic enterocolitis.
Q It may be an obvious point but I would like you to deal with it. Is it a different study than that which we looked at at page 506?
A Yes, it is.
Q There is just one aspect of this document I should ask you to deal with. It concerns Dr Berelowitz’s role within this study. Would you go, please, to page 680, at the top of the page.
“Formal behavioural assessment will be undertaken by Dr M Berelowitz at each of the 3 visits (0, 6 & 12 months) to monitor the child’s progress and seek objective evidence of developmental change (see full protocol).”
Before looking at any other reference, it may just be timely just to summarise for the Panel, please, what was the central nature and objective of the study?
A Again, it had an eye principally on safety – looking for adverse outcomes and efficacy – to see whether there was benefit, and whether there was benefit specifically in the gastrointestinal aspects of their problems and also in the behavioural and developmental aspects of the children’s problems.
Q Still staying with the question of Dr Berelowitz’s involvement, would you turn to page 715. Can you summarise the structure, please, of that page?
A This is a summary of the evaluations that a child in the trial would undergo when they visited the Royal Free, and that starts at the top with colonoscopy and biopsy, and goes through the various assessments that they will have and the various time points at which they will have them.
Q How as Dr Berelowitz to fit into that, if at all, as you understood it?
A It was my understanding that he was to undertake the developmental and behavioural assessment.
Q Turn to page 724. There is a topic “Neuropsychiatric assessment” and a number of bullet questions. Then, at paragraph 3.ii:
“Full neuropsychiatric examination will be performed on each patient by the same Clinical Research Fellow in Child Psychiatry, under the direct supervision of Dr Mark Berelowitz (Dept of Child and Adolescent Psychiatry, Royal Free). Confirmation and characterisation of the behavioural disorder will be by a structured and validated scoring system (Childhood Autism Rating Scale: CARS).”
Did you draft this?
A Yes, I did.
Q We turn to 725, and we see the Childhood Autism Rating Scale. You may remember Dr Berelowitz’s position in respect of this study. What was your understanding as to his agreement to participate in it, if any?
A I have to confess, I am rather confused about Dr Berelowitz’s role overall. I think you will remember, if you go back to 172-96 and particularly the pro forma application, he had clearly read it, approved it and signed it, and it put him in charge of conducting the diagnostic evaluations on the children in a developmental and behavioural context. That was specifically using the ADI and another instrument, the CAPA or CADA. In evidence he said that he was not capable of doing those, so I have to confess I am little confused, having undertaken to be responsible for those. I would imagine that either he would be doing them, or someone under his direction would be doing them, and similarly here, that he would be doing them or, as it suggests, that he would have a research fellow or a fellow within his department who would be capable of doing them.
Q Did you have any discussion with him before his role was, as it were, delineated in the document?
A Again, I had never heard of CARS, the Childhood Autism Rating Scale. That was not something that came from me. Dr Berelowitz also says that he has never used it, so again I am confused. He also mentioned that he was put off to some extent at least because there were American child psychiatrists in the study. I do not know any American child psychiatrists, and there never were any in this study so I am afraid that confusion persists.
Q I must ask you this directly. As far as you are concerned, did he agree to take part in this study?
A To say yes would be putting it too strongly. I simply cannot remember what the status was. It was my feeling that he had, and therefore that was the basis upon which these documents were submitted.
Q By way of background, in learning about transfer factor in the early part of 1997 – and we are now in the early part of 1998 – you mentioned the role played by Dr or Professor Fudenberg. Was Professor Fudenberg to be a participant in this study?
A Initially Dr Fudenberg was to be a participant, but for several reasons that became impractical. First of all he is elderly and frail. In truth we wondered whether he would actually survive the duration of the trial. The second is that he no longer worked in a recognised clinical and academic facility. So we opted for those reasons to enter discussions with Dr Charles Kirkpatrick, who was Professor of Immunology at the University of Colorado in Denver who was, and continued to be, a practising immunologist and an expert in transfer factor.
Q Against the background of the study as it is drafted here, and submitted to Dr Pegg, I want to now just ask you, and I hope to take this at not great length, again about the funding background. Can you turn, please, to 756a. It is 26 February. It is from you to Mr Tarhan, the Finance Officer at the School.
“Re our meeting on Tuesday, 3 March 1997…”
that is almost a year before –
“… please find enclosed two references for Alex Korda, our proposed Chairman. I have applied for references for Dr 10, our proposed CEO…”.
I will come back to that in a minute. You go on:
“In addition, Dr Kirkpatrick from Denver, Colorado, will be giving a guest lecture…”.
You have dealt with the relevance of Dr Kirkpatrick. What of the role going forward of Dr 10 as a proposed CEO and of what outfit?
A As the Panel will remember the medical school had endorsed two possible approaches to generating the funds. The first was through a pharmaceutical company and the second was through venture capital. In discussion with Ms Baker-Monckton, I think her name is, the pharmaceutical industry approach seemed a blind alley and therefore the venture capital approach was the one that was adopted. Dr 10 worked as a molecular biologist in a commercial company and over the years had reason to have contact with Alex Corder. Alex Corder was a fund manager for venture capital in the biotech area.
Q There are four documents I am going to ask you to look at and then we may pause. Page 797, please. 4 March 1998, it is a memorandum to various people, including Mr Blatch, Miss Bishop and Professor Zuckerman. I should just ask you this, what was the anticipated role of Dr 10?
A I think he was to be the managing director.
Q Of which company?
A I cannot remember what it was called at this stage, Immunospecifics, I think.
Q Why was he to be the managing director of that?
A I think he was the only one capable of fulfilling that role. I most certainly was not, I had no experience at all. He worked in a commercial company and Alex Corder was someone who raised funds and managed funds but was not an operations manager as such.
Q Dr Wakefield, I do not want to get lost in too many tentacles of funding and companies and so forth, but the central question to help the Panel is what was the purpose of the company, Immunospecifics, appearing on the stage at this point? What was it going to do in relation to the study we have just been looking at?
A It is the one option that I had been left with for raising the funds to conduct the study, and that is what the company intended to do, raise the funds from venture capital sources, conduct the study, determine whether the safety and efficacy profiles made this commercially viable and licence anything that might derive – further down the line I am not sure what the plan was, but it was to exploit it commercially to get a financial return.
Q At this stage who were the potential beneficiaries if that were to come to pass?
A What was to happen, I think, is that the rights to the patents were to be subsumed into the company for which the medical school, the owner of the patents, would then take a share in the company, so the medical school would benefit, the individual shareholders would benefit and the venture capitalists who had put up the funding would also benefit.
Q As matters stood at that date was that, at any rate as far as your experience went, in any way unusual?
A No, after that initiative during the Thatcher era to create what were called campus companies, these were springing up all over the place and there were many within the Royal Free and University College. They are very commonplace now.
Q Page 797:
“Andy came to see me with two of his colleagues who expressed an interest in setting up a company and acquiring the patents from the School.”
Again, the rest of the memo is self-evident, would you like to comment on that?
A Again, this is an example of one of the interactions between proposed members of the company and representatives of the medical school which was seeking to set the whole thing in motion.
MR COONAN: That is all I am going to ask you about the funding history; others may ask you more questions about it. I am going to come to the last section and, sir, I note the time. It will not take a long time but I want Dr Wakefield to feel able to deal with this last section.
THE CHAIRMAN: I do feel we have had a lot of evidence today, so if it is not too inconvenient we will resume the hearing tomorrow morning rather than continue now.
MR COONAN: It is certainly not inconvenient to me, I can easily deal with this tomorrow morning.
THE CHAIRMAN: That will be helpful.
MR COONAN: Mr Sheldon has reminded me, and I am grateful. After I have dealt with this short section – and I can tell you in advance it deals with safety issues in the documents – we will then be moving to the Lancet. What we have done is collate from volumes 2 and 3 of your bundles a clip of all the Lancet material which is in the two main bundles so that you have it, if you wish it, in one complete clip so that you can read it rather than going from one volume to another and so on over a span of years. You may or may not find this helpful but we took the liberty of photocopying it as a clip so that you might, if you felt it appropriate, either read it in advance of this evidence or if not subsequently so at least you can have it available. You may think it is more paper.
THE CHAIRMAN: I am sure we will find this helpful but I am not quite sure whether we will be in a position to do any more reading today after quite a lengthy day today.
MR COONAN: Far be it for me to suggest that, but it was a question of whether you might consider reading it tomorrow morning before the evidence continues, or we go straight into the evidence. I was simply giving you the opportunity, if you found it helpful.
THE CHAIRMAN: Can I make a suggestion, if that is acceptable to you? If you have no objection – and I am also looking at Ms Smith as well about it and also the Legal Assessor – maybe we could be circulated with this document now and then I will talk to the Panel members and if they wish to do the reading tomorrow morning we will pass a message to you through the Panel Secretary to give us maybe half an hour or so.
MR COONAN: That would be very helpful.
THE CHAIRMAN: If the Panel members feel that they would wish to go straight into it, then also we will communicate it to you.
MR COONAN: That is very kind; either way I am content.
MS SMITH: Two things concern me, sir. I do not want to inhibit Mr Coonan of course from conducting his case in whatever way he wishes, but I do wonder whether the Panel may have written on their own copies of some of the documents in relation to the Lancet. I do not guarantee that what Mr Coonan identifies as being the relevant Lancet documents will necessarily be what I identify as being all the relevant documents on that subject, so it is going to be a duplication of papers that you already have which may not be as helpful to you as the ones you have got, but if you feel it would be more helpful then I am in your hands. I do just wonder if some of the Panel members may find they have notes written all over their Lancet papers.
THE CHAIRMAN: This is true, either we have written certain things on our documents or we have underlined and highlighted certain parts of the document. I still wonder if it may be helpful to keep them all together rather than keep jumping, but can I suggest that you have a look at those documents and see if you are content for those documents to be circulated tomorrow morning, because we are not going to have a look at them tonight.
MS SMITH: I am happy to do that, sir. As I say, I do not want this to become an agreed bundle in any sense because it just seems confusing to us. Quite frankly, we too have written all over the documents.
THE CHAIRMAN: Maybe you could just look at it to be sure there are no new papers in there.
MS SMITH: That, I have to say, had not entered my head, I was not suggesting anyone had descended to those levels of iniquity, I am assuming it is all in the bundles.
The other alternative would be to give you a list of the page numbers that are in that bundle so you have the page numbers of the relevant documents which you could have a look at tomorrow morning. I am quite happy, if Mr Coonan wants to talk to me about it, to talk to him about it.
THE CHAIRMAN: Let me talk to my Panel members this afternoon and we will pass on a message to you tomorrow morning. If we want to spend a little time reading those then we will ask for those bundles to be given to us and we will do that, otherwise we shall go straight into the public session.
MR COONAN: I am sorry I opened my mouth. Ms Smith has had this for days and in the spirit in which I said it to you, it is only there to help if you want it, if you do not want it that is fine.
MS SMITH: I do not understand what Mr Coonan means by I have had it for days, I do not know anything about it at all.
MR COONAN: I thought it had been served on you.
MS SMITH: Mr Coonan may want to retract that, I certainly have not seen a bundle of Lancet documents.
THE CHAIRMAN: We have all had a long day so can we call it a day now and tomorrow morning I am quite sure you will both know what exactly you are intending to serve and whether Ms Smith is happy or not. In the meantime I will also have a word with the Panel members as well. We will resume at 9.30 tomorrow morning.
The Panel adjourned until 9.30 am on Friday, 4 April 2008