Tuesday, February 7, 2012

Day 57 GMC Fitness to Practice hearing for Andrew Wakefield

GENERAL MEDICAL COUNCIL

FITNESS TO PRACTISE PANEL (MISCONDUCT)


Thursday 10 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




CASE OF:

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



(DAY FIFTY-SEVEN)










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



A P P E A R A N C E S


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

MR KIERAN COONAN QC and MR NEIL SHELDON of counsel, instructed by Messrs RadcliffesLeBrasseur, Solicitors, appeared on behalf of Dr Wakefield, who was not present.

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

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








I N D E X

Page No



ANDREW JEREMY WAKEFIELD, continued

Cross-examined by MR MILLER 1
Cross-examined by MR HOPKINS 27


THE CHAIRMAN: Good morning, everyone. Could I give the usual reminder about mobile phones being switched off while in this chamber? Mr Coonan, I think you had finished your examination in chief, except for the fact that we were still hoping to see the video of the conference where the lecture was given.

MR COONAN: That is right. Arrangements are still in hand to achieve that but I cannot lay anything before you at this stage. It will have to be provided to you a little later but the fact that it will be laid before you a little later I do not object to. If anything emerges out of that coming in late then, obviously, I would respectfully reserve my position, but I do not object to you receiving it later on.

THE CHAIRMAN: Thank you. If that is acceptable to you all we will at some stage later on is interpose it in the proceedings when it is available, look at the video and we will have the transcript, if that is practicable. We will continue on that basis.

Mr Miller, I think you are going to cross-examine Dr Wakefield on behalf of Professor Walker-Smith.

ANDREW JEREMY WAKEFIELD
Cross-examined by MR MILLER

Q I have got a number of questions I want to ask you but it is not going to last very long, they are discrete topics I want to deal with because you have covered the ground very thoroughly in your evidence. Can I start with one point of clarification: during the period 1997 to 2000 we have seen documents relating to two suggested types of treatment for children who were affected in the way in which The Lancet 12 children were affected, and they overlap, at least discussions overlap, but I just want to get our bearings as to the timings of these suggestions about treatment, because in the end neither trial came off, did it?
A Correct.

Q As far as Mesalazine is concerned, which was an anti-inflammatory that was commonly used at the time, this was a trial that was in contemplation, specifically directed towards children with these conditions, that trial, which is totally separate from the transfer factor proposed trial, was in contemplation from some time around the spring of 1997 until some time in the summer of 1998.
A Yes, it is my belief that is correct.

Q We have seen some documentation and we may in due course see some more but there is talk about a link-up with Dr Falk of Pharma GmbH in Germany, a collaborative trial with that company, which looks to start in about June, I think, 1997, at least the discussions started at that time, and eventually we saw with Professor Zuckerman when he gave evidence that by May 1998 there was a letter from Dr Falk himself saying, “I’m sorry, we don’t think we are going to back this trial financially and you ought to look to a UK-based drug company to provide the financial backing for you.”
A That is correct.

Q But throughout that period of almost a year, 19971998, it was still in contemplation that a clinical trial would take place specifically for the treatment of this type of child.
A Yes.

Q With that in mind, I think the research nurse who dealt with research aspects for you was following up children who had been given a therapeutic trial of the various drugs to see how they reacted to them in two ways, first of all, as far as their gastrointestinal problems are concerned, and, secondly, as far as their behavioural problems were concerned.
A Correct.

Q Did this involve keeping in contact with the parents and in some cases asking them to provide diaries over a period of time to monitor the reaction to the treatment?
A Yes, it did.

Q That was done in order, as it were, anecdotally to see how they reacted as a sort-of database of framework, a data point I suppose, from which to launch a clinical trial?
A Yes.

Q I think you said it was for that reason that you had an interest in how children were reacting to Mesalazine/Sulphazalazine because it would be helpful in putting together the clinical trial that you knew what was going on.
A Correct.

Q Can I now turn to another topic, and it is the coming together of the study group, if I can put it that way? You have given evidence about the coming together of a clinical and a research team which became involved in the clinical and scientific investigation of, amongst others, those whose cases were dealt with in The Lancet paper.
A Correct.

Q We have to keep an eye on the fact that, although it ends up as a team, it comes from very different disciplines.
A Yes, that is correct.

Q We have identified during the course of these proceedings the clinical elements of that team, which obviously include the three consultant gastroenterologists.
A Yes.

Q That is Professor Walker-Smith and Professor Murch, and Dr Thomson, as well as the doctors in training, Dr Casson, Dr Malik, who contributed to the clinical study, and whose names appear as authors of the paper.
A Correct.

Q Dr Harvey, and in some way Dr Berelowitz within the hospital clinical set-up who examined some of the children.
A Correct.

Q And Dr Sue Davies who was part of the NHS care and investigation of these children was providing within a relatively short period after investigation her results of the histopathology for the purpose of identifying what, if anything, was going wrong in these children’s guts.
A Correct.

Q They are all involved at around the time of investigation and would be considered to be the clinical team looking after these children.
A That is right, yes.

Q There are others who come in after that when the question of what exactly is going on has to be considered and they make up the rest of the team, the scientists who are not concerned with providing clinical care or diagnosis but are trying to identify what is going on from the histology that has been obtained.
A Yes.

Q And you are part of that scientific team but there are others, Dr Linnell, Dr Anthony and Dr Dhillon in that role, all of whom come in at a time when decisions have been made as to what investigations need to be carried out and, if necessary, what treatment has to be given?
A Correct.

Q So they all make up the team and come together to some extent but the scientific side appears to have taken over after the child had been investigated and the clinical team had made its decisions as to how to proceed.
A That is correct, yes.

Q In giving detailed evidence about when the team began to come together, which I think you gave evidence about on Day 48/page 33, early in your evidence, you suggested that things started to be discussed with Professor Walker-Smith before be left St Bartholomew’s, that appeared to be your evidence, and that, to be fair, you say was your recollection although we obviously had no documents of discussions taking place between anybody at that stage, do we?
A That is correct.

Q Can I suggest that that coming together discussion happened later than the end of 1995, certainly later than Professor Walker-Smith’s transfer to the Royal Free, and can I explain why, and then I would like you to deal with it? We have looked at the case of Child 2, who, although the first person to be seen by Professor Walker-Smith, was in fact seen at a different time, in 1995. Can we get some dates on that from what we do know? We have been told by you that you had suggested to Mrs 2 in 1995 that she should try to obtain a referral of her son to Professor Walker-Smith while he was still at Bart’s?
A That is correct.

Q We know that Dr Wozencroft did make that referral on 29 June 1995, and just for the record, that letter is to be found in the Royal Free Hospital notes at page 197, and we also know that Child 2 was seen by Professor Walker-Smith on 1 August 1995, still at St Bartholomew’s, and again the reference is in the Royal Free Hospital notes at page 125, and Professor Walker-Smith saw the child in his outpatient clinic at Bart’s, and then we went through the history of this child’s investigation and treatment. We saw that Professor Walker-Smith corresponded with a large number of doctors, different specialists, at about the time, suggesting referrals to others, Dr Beattie, Dr Batt, corresponded with Dr Cavanagh at the Chelsea & Westminster Hospital but in the end, on 13 September 1995, he wrote to Dr Wozencroft and others, the general practitioner as well, effectively saying that there was nothing that he felt he could do for the child and suggesting that he should have a B12 investigation at the Chelsea & Westminster Hospital and that he should be managed by a locally based paediatric gastroenterologist and he suggested Dr Beattie.
A Correct.

Q So that is all happening on 13 September 1995, and that was after Professor Walker-Smith had moved to the Royal Free because the move took place on 1 September. So if, as your recollection goes, according to your evidence, Professor Walker-Smith was in effect storing up cases which he knew about at Bart’s until he got to the Royal Free then it would be surprising, would it not, if he was saying, having got to the Royal Free on 13 September, that as far as Child 2 and Mrs 2 was concerned, as far as he was concerned he could nothing more for her, and that would be surprising, would it not?
A Not necessarily. I fully accept your description of the documentation. I have two memories, or one memory and one piece of evidence, and the first is a memory that I had many contacts from parents which were discussed at some stage pursuant of the first contact by Mrs 2, and there was a decision to defer any such referrals until transfer. That does not necessarily mean to say any referrals were arranged, or indeed anticipated, in fact it is just that if there were to be any they should be deferred until transfer. That is a memory. The documentation that I have to go on is contained within the ethics approval and is that document dated in October, and clearly that is beyond the point of transfer.

Q Yes, undoubtedly, that would be within a matter of five or six weeks of the transfer, which would suggest that everything was done and dusted, or close to being done and dusted, by then. You have no actual memory of that document or indeed where it came from, do you?
A Only by virtue of the description, the title described within it, but the concept had been coming together, at least in my mind, over time to put these documents together at least in provisional draft form really does not take a great deal of time and I think that all I can do in these circumstances is rely upon the documentary evidence that is to hand.

Q There is no evidence that points us to anything because it is the only document that we have that has a date on it but if you just put this in the overall context, it looks to be rather strange that as early as that, effectively, a plan has been worked out, which includes a consent form for future investigations: could this be a cut and paste document where you have used a consent form from some other trial that was in contemplation, because it looks as though it is a computer generated date, does it not, at the bottom of the paper?
A I have not been involved in the design of a consent form before so that would not explain it, and, as I say, all I have is the documentary evidence that is there to go on.

Q Can we just look at some other factors, different points: Dr Thomson did not arrive at the Royal Free until November 1995, he came from Birmingham, as we know, he did not come from St Bartholomew’s, so any input that he might have had to a clinical protocol could not have taken place until after that.
A Correct.

Q To the extent that he was the consultant paediatrician who made the suggestion that any investigations proposed for children should include a lumbar puncture, his input could only have taken place after 1 November 1995?
A That is correct.

Q Can I put to you, Dr Wakefield, Professor Walker-Smith’s recollection about the time and see if you can deal with this, and this will be, I anticipate, his evidence. The move to the Royal Free Hospital took place, the start up date at any rate was 1 September 1995, and the move was a huge endeavour, was it not?
A Yes, it was.

Q Because it involved moving the clinical and research elements from two London sites into a purpose-built department at the Royal Free?
A Correct.

Q I think a whole floor was added and they took up the whole floor and it was dedicated for their paediatric gastroenterology department, and they had to set up the running of the unit in which, as it turned out, the autistic patients were only a very small part.
A Correct.

Q His recollection – and this is what he will tell the Panel – is that you and he only began to discuss them as an entity at the beginning of 1996, and then there were discussions which became more focused and involved others and culminated in a meeting which most participants attended in April 1996?
A Certainly there was an increasing intensity of discussions through that period, culminating in that meeting in April, yes.

Q Would you just look at this? Would you look at it first? (Same handed) Is that your handwriting?
A Yes, it is.

Q Do you recollect this document?
A No, I do not, but that is not surprising.

Q No, of course, but you would accept that it is something that you are writing, and we will look at its content in a minute, but you accept that in some form this was a document which you wrote?
A Correct.

MR MILLER: Sir, could I hand up this document, which is not dated but I ask you to put it into FTP1 as page 93A. (Same handed). Do you have a copy?
A Yes.

Q On the face of it – and you will correct me if I am wrong – this is you saying to all of those who are going to become involved asking them for various things, and the timing looks to have been some time in March, one imagines, from this, perhaps the end of March. It says:

“Required”

and they are bullet points.

“ – Comments to AJW”

which is you.

“Costings of your specific element”

Clearly, some of the scientists would have to provide costings of what it was going to cost for them to produce whatever they had to do?
A Correct.

Q Because they can only work on the basis of people paying for their work. These had to be done by 2 April.

“Then

AJW to arrange meeting with all collaborators. Please supply 3 possible dates and a time for April.”

This looks like a time quite shortly before we get to a meeting in April, and you are asking everybody for their comments?
A That is correct.

Q And to that extent we can read into this that the clinical and scientific trial had not been finalised by that date because this is leading up to everybody getting together. In fact, most people did attend that meeting, did they not?
A Correct.

Q Can we then just look at it from a slightly different point of view? The trouble is, we have so much documentation in this case but in this area there is not any. If parents were contacting you before Professor Walker-Smith moved to the Royal Free, that is before 1 September 1995, and you were waiting for the move before setting up referrals, and it was through you the referrals were going to come, not as a referring doctor but you were saying to a parent, “You need to get a referral from your general practitioner or paediatrician who is looking after your child”?
A Correct.

Q But you had to point them in that direction if they made an approach to you?
A Yes.

Q If that was happening before 1 September 1995, then it looks as though over five months went by before the first referral was made, which is in February 1996, Child 3. Although you say effectively cases were being identified, nothing happened for five months until February 1996?
A What I would have done in those circumstances is to say that we are considering – it is being considered – the possibility of accepting referrals as being considered, but “There is nothing planned at the moment, nothing we can do and these need to be deferred, and you may wish to make contact in the future.”

Q Thank you, Dr Wakefield. It is trying to find something in an area, with a document in every case, we do not have any real signposts except, as you point out, the consent form date at the bottom, printed at the bottom.
A I fully appreciate that.

Q May I ask you a bit about The Lancet paper, and we do have a lot of documentation here. You were the draftsman of The Lancet paper, subject to contributions being made by others involved in its publication, other authors. You corresponded with The Lancet, with the editorial staff, anyway, presumably when there was a revision or a suggestion came back to you and you dealt with it in collaboration with the other authors?
A Correct.

Q You sent, as you say, copies to all the contributors for their comments. It looks as though the last draft that was sent out, anyway, was the one that was sent out with the covering letter that we have inserted at FTP2 at page 616a. Could you just turn that up, please. It is a green document. Do you have it?
A I have it, yes.

Q I think this was inserted when Dr Berelowitz was giving his evidence because he was one of the recipients, although this copy was in fact Professor Walker-Smith’s copy. You can see there is a tick against his name. It is sent to all the other authors, is it not?
A Correct.

Q It is dated 8 October, and you have said:

“Please find enclosed final version of the first Lancet paper on this subject describing the syndrome.”

A Correct.

Q I think you were given to understand, again from Dr Berelowitz, that the document that we have starting at page 758 is the document that would have accompanied that. That was in the original bundle. It is in the same volume.
A Correct.

Q I am going to come back to that, but not in any great detail, in a moment. That just gets us to a point in October where we have certainly something which is closer– in your contemplation anyway – to the final draft of the paper. Can we just look at some of the events that occurred before publication, Dr Wakefield. First of all, the event that involved Pulse, the GP medical journal. In July 1997 you spoke to a reporter, I think, of Pulse, as far as you were concerned off the record?
A Correct.

Q And I think most people know, I think it is a medical journal which is directed at general practitioners. I think, putting it neutrally, it caused a bit of upset when it received attention from the media?
A Correct.

Q Can I ask you to look at three letters that we have not seen up to now, just around this time? To put it in context of what happened with Professor Calman and the meeting that subsequently took place, these are three letters which again we can insert into FTP2. They have their numbers already on them.

THE CHAIRMAN: Just for the purposes of the transcript, these are 497a, 499a and 500a.

MR MILLER: Thank you, sir. (Documents circulated) I want you to correct me if I am wrong about this, Dr Wakefield. Pulse got hold of an idea that there were a number of studies about to come out which linked MMR and autism. In general terms, that was the idea that they got, and chose to publicise. Is that right?
A Yes. This came about because I had had a meeting with Tessa Jowell, when she was the Shadow Minister for Health. At that meeting was the MP, Llew Smith from Blaenau Gwent and, unbeknown to me, following that meeting, Llew Smith contacted Pulse and had a meeting with them or an interview. At that meeting with Pulse he disclosed the contents of our meeting with Tessa Jowell. Pulse contacted me and, as I understood off the record, asked for my comments, and I was very limited in my comments, but I confirmed that we had had such a meeting and we anticipated publication of data. Unfortunately, and again unknown to me, an article appeared which reiterated the contents of my meeting with Tessa Jowell, and that was most unfortunate.

Q It led, I think – the documents are in the bundle – to questions being asked in Parliament?
A Correct.

Q It also led to an offer from the Government’s Chief Medical Officer to have a meeting with him and the Health Minister to discuss the implications?
A What in fact happened was that following that meeting, Tessa Jowell offered, pending a successful election outcome, to meet with us should she then become the Minister of Health and that was in fact what happened.

Q The meeting, I think, was set for 10 September 1997. Is that right?
A Correct.

Q That is the background that takes us a little bit beyond this correspondence. Can we just look at these letters – 497a first. It is 29 July 1997.

“Dear Andy

Re: MMR

Out of the blue today, I was telephoned by a rather distraught Roy Pounder telling me that there was an explosion of interest in the media today concerning MMR and autism. One of our parents [Mrs 6 and 7] had been approached by the media and was very distressed. She felt that the hospital had given her name. I telephoned her to reassure her. Roy told me that all this was triggered by your interview to the GP Magazine Pulse. He faxed me the text. I could hardly believe what I read. How can you talk about the papers to be published when they have not appeared in press? Why did you give such an interview at this delicate time when we are so close to publishing/ Simon and Mike”

that is obviously Murch and Thomson –

“are both very upset and concerned that our professional reputation as collaborators is in jeopardy. You did not mention this Pulse interview to me when you invited me to meet with Tessa Jowell.

On reflection I cannot see why you had arranged this meeting with the Minister and indeed Calman before the papers were published. I feel my own position is very weak defending unpublished data.

This whole crisis has really soured relationships all round. I am doing my best to defend you but simply cannot understand why you gave the interview with Pulse and you did not warn me or Roy Pounded in advance.

I hope we will have a chance to talk before I go on holiday on Tuesday next week.”

You, I think, had been on holiday, had you not, when the balloon had gone up?
A Correct.

Q And you replied to that. In fact you replied on the next page, 30 July, 499a. This was a letter to Professor Walker-Smith, Dr Murch and Dr Thomson. Do you see that?
A Yes.

Q
“Dear John, Simon, Mike

I understand there has been a little media attention since I left for my annual leave. Just a short note to reassure you that the source of this information (Pulse) are not privy to any information. They contacted me the other day to ask if there had been any further data. I told them that there was nothing at present but that we hoped to publish further data in the next 6 months. They appear to have made quite a story out of this quote siting that they will be revealing further data in the near future. This is an example of journalistic jingoism, presumably in the absence of any other news to report. Nonetheless it appears to have precipitated Kenneth Calman in to action and he has written to me asking for further details. Roy has this matter in hand. It would seem that Calman would be present at our meeting on 10 September.

I just wanted to reassure you that no confidences have been breached and no data has been revealed. Please feel free …. although this afternoon I will be gone fishin’!”

In effect you were saying they had made a quote out of nothing, that you had not revealed any data?
A Yes. I had no seen at this stage, being away, the contents of the Pulse article, I do not believe. I only became aware of the extent to which LLew Smith had breached the confidence of that meeting with Tessa Jowell and clearly there were major ramifications of that.

Q We can see again, about the same time, a document we have already looked at. It is 497 in the same bundle. It is dated 29 July, so the day before your letter, from Sir Kenneth Calman.

“I understand from the media that you have new evidence for a link between MMR immunisation and Crohn’s disease and autism, which will be published within the next six months. The Department is getting several enquiries from the media about this and it would be helpful if you will let me have a copy of the research evidence to which you refer, or an outline of the projects.”

That is the reference to Sir Kenneth Calman in the letter that you wrote to your clinical colleagues?
A Correct.

Q Then 31 July, page 500a.

“Dear Andy

Re: MMR

I was so glad to have your letter yesterday and also to speak to you. However the events of the last day or two has revealed a tremendous potentiality for controversy within the hospital here about the work particularly in relation to autism. Professor Brent Taylor apparent was ‘incandescent’ Simon tells me at the Paediatric Speciality Group Meeting. I think it is absolutely essential that no work concerning autism is made public until the data appears in press. I also think it would be very helpful if you had a long and detailed discussion with Simon Murch and indeed endeavour to make the case to Brent Taylor. Simon will brief you about a number of ongoing anxieties. Basically Simon is very concerned that our professional reputation could be damaged by being associated with work which is prematurely leaked to the media. I know that you certainly don’t intend to do this but you need to convince Simon and the others.”

You can understand those feelings being expressed, can you not, Dr Wakefield?
A Yes. I think that we all felt rather betrayed by the MP’s disclosure and it clearly created a major problem for us as collaborators at the Royal Free.

Q But it arose out of meetings that you had had at which they had not been present, and they were saying from the clinical side, “This should not happen because it may undermine the quality of our work”?
A Yes. I do not think they were saying that a meeting with Tessa Jowell should not have happened.

Q No, no, but the leaking of that meeting?
A Correct, absolutely.

Q And it went beyond the gastroenterologist, did it not, because we have seen in the main bundle at page 504, so at exactly the same time, a letter which Dr Berelowitz wrote top Professor Walker-Smith on 5 August. It is addressed to Professor Walker-Smith but a copy was sent to you and to Dr Murch, Professor Taylor and Professor Pounder, we can see from page 505.

“Dear John

It seems clear from the events of the last few days that our research has already attracted complex publicity and is likely to attract more publicity when it is published in The Lancet. Furthermore, it has the potential for affecting vaccination up-take if it has not done so already. My own view is that it would [be] unwise to draw strong conclusions from our preliminary research about the wisdom of vaccinating children.
Therefore, I would like to be sure that two issues in our paper are emphasised: firstly, we need to check that we have spelled out the fact that the onset of autism and disintegrative disorder always occurs after the end of the first year of life and so no causal connection between vaccination and autism could possibly yet be drawn from our findings so far. Perhaps you would be good enough to re-read the manuscript and make sure that this issue carries the right sort of emphasis and that the possible causal link is not over-stated.

Secondly, my preference would be to make a clear statement in the paper about vaccination. I would like to say: ‘This research is of a preliminary nature and we would not wish General Practitioners or the general public to draw strong conclusions from it about whether or not individual children should be vaccinated against measles. Guidance about vaccination should be taken from the Department of Health in the usual way. If, in time, our further research leads to firmer conclusions, we might then have some comments about the risks of vaccination.’

Lastly, I have had some second thoughts about our title. I think that we should call this condition a ‘development disorder’ rather than a regressive behavioural disorder. This title is technically more correct, and will cut off in advance one potential area of criticism.”

Did you take on board what Dr Berelowitz was saying? There are three aspects to it, obviously, the first about the suggested coincidence about autism and MMR coming in the same year, and we are going to come to that, that would seem to be the first thing; the second appeared to be a health warning about MMR, not against it, saying we should continue to do it; and the third was about the title, so there are three elements of that letter, albeit not addressed to you. Did you take all three of those on board?
A I certainly read the letter and I believe that certainly in the context of the first point I had a discussion with Dr Berelowitz because, if I can just reiterate what he says here,

“check that we have spelled out the fact that the onset of autism and disintegrative disorder always occurs after the end of the first year of life …”

We had a discussion about this because this is not consistent with the lecture that he had given us on this matter some time earlier, and I referred to a graph that he had presented to various collaborators which described the developmental trajectory of children with autism – classical autism – and children with disintegrative disorder. He showed in that graph that the development of classical autism started in the first year of life and therefore it was somewhat perplexing that he was now saying that the onset of autism occurs after the end of the first year of life, so I think that that issue led to some modification of his position.

Q It may be necessary to look at it or it may not, but I think that when you were giving your evidence-in-chief you said that it did appear at some stage in one of the drafts but in fact is not to be found in the final paper, so maybe that discussion took place between the penultimate draft and the final paper.
A Correct, I am sure it did.

Q As far as the suggestion about MMR and supporting MMR is concerned – this is the last paragraph on page 504 – did you consider that sufficient guidance was there within the paper as it was ultimately published about the preliminary nature of the findings that had been made?
A Again, this was discussed. The purpose of this paper, as I think I said in evidence, was not to recommend vaccination policy, that is not what it was about, and so we demurred from that particular position.

Q And as far as the title was concerned, did that change in accordance with the advice that had been given by Dr Berelowitz at the end of that letter?
A Yes, it did, and when the galley proofs of the final document were distributed he made a further recommendation and that is that the word “pervasive” should precede developmental disorder.

Q Certainly the document that we have looked at, the round robin as it were, when you sent what you thought was the final draft, by that stage in October 1997 the title had changed in accordance with the suggestion made at the end of this letter.
A Correct.

Q The draft which we have starting at page 758 you have agreed was around the last of the drafts that were sent out, and that was behind the letter which has been produced, the green letter, showing that it was sent out in October – we looked at it at the beginning of your evidence today.
A Yes.

Q I believe that that draft is the same draft that was sent to Sir Kenneth Calman which we have starting at FTP2 page 648, sent under cover of a letter of 16 January 1998 by Professor Pounder.
A Mr Miller, could you direct me to the first draft you referred to? I have the one at 648.

Q Page 758.
A Yes.

Q So what was said to be the final draft is certainly the same draft as is sent to Sir Kenneth Calman on 16 January 1998 by Professor Pounder. That is all I want to ask you about the paper itself, you have given detailed evidence about that, but finally on this point I would just like to ask you about some of the correspondence between you and Professor Walker-Smith which occurred shortly before publication. It is a long time ago since we looked at that correspondence, I think when Professor Zuckerman gave his evidence. It starts at FTP2 at page 646A and this is a letter from you dated 15 January, copied as we have seen on page 646C to Professor Zuckerman, Professor Pounder, Dr Murch, Dr Thomson and Dr Berelowitz. This is 15 January and in terms of the paper itself,

“Firstly, the paper has been officially accepted by The Lancet after some minor revisions. They will be sending proofs next week and I will pass one on to each of the authors.

I felt that in view of the imminent publicity regarding our work, it was important to write and clarify my own position. Clearly, pending a press-briefing or other communications with the press, which now seem inevitable, we need to have considered our points of view well in advance of publication.”

At that stage, just pausing there, Dr Wakefield, had the press-briefing been set up?
A Yes, since I refer to it I believe it must have been.

Q
“There may be points upon which we disagree, but I do not think that this is a problem, as long as that is made clear. If we can both recognise and respect each others position, then there should be no ambiguity. I have thought about this issue almost continuously over the last five years, firstly in relationship to inflammatory bowel disease and latterly autistic enteropathy, and I have tried to set this out below, as a template for a more detailed discussion.

In addition to our own work and that of others, my opinion is also based upon a comprehensive review of all safety studies performed on measles, MR and MMR vaccines and re-vaccination policies. This now runs into a report compiled by me of some 250 pages, which I am happy to let you see. In summary, the safety studies are derisory, and appear to reflect sequential assumptions about measles vaccine safety, MMR safety and, latterly, two dose vaccine safety, where each assumption has potentially compounded the dangers inherent in the first.”

Can I again pause here? This is a letter which is predicting media interest in the results of publication and is setting out your personal concerns about vaccination, that is right, is it not?
A That is correct.

Q And it is prefaced on the basis that you have done the reading around the subject, particularly on the safety aspects of immunisation.
A Yes.

Q You go on in the letter:

“In view of this, if my opinion is sought, I cannot support the continued use of the polyvalent MMR vaccine. I have no doubt of the value of the continued use of the monovalent vaccines, and will continue to support their use until the case has been proven one way or another of the measles link to chronic inflammatory bowel disease. I believe that 1998 will see some conclusive data in favour of the measles link from both our own work and the USA. I recommend that measles vaccination is deferred in children with a strong family history of IBD.”

Then you go on to deal with the position about vaccination generally on the next page, 646B, the position of the Department of Health and the house of cards crashing to the ground which you went through with Mr Coonan when you gave your evidence. If we just pick it up in the last two paragraphs on page 646B:

“In an attempt to avert the House-of-Cards collapsing, I will strongly recommend the use of monovalent vaccines as opposed to the polyvalent vaccines. This will not compromise children by increasing their risk of wild infection, and may reduce the risk of an apparent synergy between the component viruses that has been identified by Dr Scott Montgomery as a risk factor for inflammatory disease and may well be a risk for autism in our children, currently under investigation.

I appreciate that you cannot (or may feel that you cannot) support this stance, and I completely respect that. I value your opinion and your friendship.”

Dr Wakefield, that was, although addressed to Professor Walker-Smith, directed equally at Dr Murch, Dr Thomson and Dr Berelowitz.
A And Professor Zuckerman.

Q Yes. The slight difference is that he had already been in correspondence with you or you with him at that point; the other four were collaborators in the paper which was about to be published.
A Correct.

Q Can we then just look at the response to it at 673A. I believe this originally had a D number but it is A now. This is a reply to you from Professor Walker-Smith, 21 January, and I should also say that the joint signatories are Professor Walker-Smith and Dr Murch.

“Thanks very much for your letter to clarify your position before the press conference.

Our position is that the new paper as published does not present direct evidence for any implication of MME vaccine although such evidence may be forthcoming in the second paper and other work in progress.

For us it seems inappropriate to emphasise the role of MMR vaccine in publicity about this paper. Its main thrust is to describe for the first time bowel inflammation in children with autism and so suggest a pathogenic mechanism for autism.

Even when pressed by journalists we feel no specific information about the role of MMR should be discussed at a press conference. Our position must be to maintain a public agnosticism about the risk of MMR and for the moment support government policy concerning MMR until more firm evidence is available for us to see ourselves.

In private our view is that the government should institute urgently a comparative study of MMR and monovalent vaccines. This is more likely to happen if we refrain from publicly attacking government policy until we have published evidence.

We continue to support our collaborative research with you and we respect very much passionately held views and your concerns for the children themselves. We value immensely your huge contribution.”

You respected their position, did you not, Dr Wakefield?
A Absolutely.

Q And you had indeed, when you wrote the letter to them, predicted that that might be the view that they would take.
A Absolutely.

Q Indeed, as you know and as Professor Zuckerman confirmed when he gave his evidence, Professor Walker-Smith and Dr Murch and Dr Thomson issued a press release after publication which we have at FTP2/782A. Professor Zuckerman, who seems to have been involved in some of the press element of this paper, confirmed that this was issued by the signatories here, Professor Walker-Smith, Simon Murch and Mike Thomson.

“The Lancet paper of Wakefield and Others is important as for the first time it describes significant bowel inflammation in children with autism and related disorders. This opens the possibility of developing improved understanding concerning how autism occurs.

As to the possible risk of MMR, we support present public health policy concerning MMR. However it is important that evidence be collected as soon as possible to establish whether there is any role for MMR as a cause of the bowel inflammation found in children with autism.”

It is taking up exactly what they had said in the letter that they had written to you.
A Absolutely.

Q Once we see the whole of the press conference the Panel will see, and I am sure you can confirm, that Professor Walker-Smith was not at the press briefing that took place after publication.
A That is correct.

Q The last topic that I want to ask you about, Dr Wakefield, is transfer factor. There are two aspects to your evidence on transfer factor about which I want to ask you: the proposed clinical trial, which we have already touched on this morning, and secondly the treatment of one particular child, child 10, and although perhaps wrong chronologically I would like to deal with them in that order, so I would like to look at the trial first. For my purposes I would like to start with your application for a patent, and the patent was in respect of a new vaccine for the elimination of MMR and measles virus. It is a long title and I ought to ask you to turn this up, it is FTP2, page 479. This gives us a date, 6 June 1997, and then the heading on page 480 is: “The pharmaceutical composition for treatment of IBD and RBD”. I have temporarily mislaid the title of the source of this, but it was for a new vaccine for the elimination of MMR and the measles virus and the pharmaceutical or therapeutic composition for the treatment of IBD (inflammatory bowel disease), particularly Crohn’s Disease and Ulcerative Colitis and regressive behavioural disease (RBD).
A Correct.

Q You made the strong point that as a vaccine this cannot be put alongside MMR for the scientific reasons that you gave in your evidence.
A Correct.

Q So you are not putting up something to compete with it, it addresses a different point?
A Correct.

Q You used the acronym RBD, regressive behavioural disease, was that one of the intermediate stages in the description of the behavioural aspect of the autism spectrum problems that these children had?
A It was and it was rather imperfect but it was one that was adopted by Peter Stebbing, the patent lawyer.

Q To be fair to you, the letter we have just looked at, in August 1997 from Dr Berelowitz, says for the first time I think, “We should not be calling it regressive behavioural disease: we should be calling it developmental disorder.”
A Correct.

Q But this looks as thought it pre-dates that letter from Dr Berelowitz.
A That is correct.

Q That is where we get RBD at that time, in June 1997 that was the description that was being given by those who were advising you on the psychiatric or developmental aspect of these children?
A I believe that is the case, yes.

Q On page 480, which deals with the pharmaceutical composition of treatment, you say this was written by your patent attorney Mr Stebbing, is that right?
A That is correct.

Q But obviously from material provided by you.
A Absolutely.

Q I think as you said in your evidence on Day 53/38, he had had a scientific overview from you, and page 479 shows the filing date I think of 6 June 1997, is that right.
A 6 June, yes.

Q The filing date is 5th and the letter is 6 June.
A Sorry, 5 June.

Q That scientific overview, which you had provided for him, included, or was based upon, the then published literature that was available at the time.
A That is correct, yes.

Q In other words, before the patent could be applied for you had to assimilate the scientific literature and place your synthesis of it before your patent attorney, and that is then translated into the patent application.
A Yes, at that stage I had done an extensive review of the literature on transfer factor.

Q And that scientific overview and scientific literature research would have involved research on safety of transfer factor?
A Very much so, yes.

Q It looks as though this patent was filed while the 1998 Lancet paper was still in draft, just on the dates: if it was filed on 5 June 1997, that is eight months before publication of the paper.
A Yes, and we had some documentary evidence of the fact that a first attempt to get publication had been submitted to The Lancet by that time, yes.

Q I am sorry, we have seen that about that time it had been submitted for publication but we know that there was some redrafting that followed, but certainly it was before publication?
A Yes.

Q An indication for that might be the use, as we have already indicated, of RBD rather than what subsequently became the title for the behavioural problems. As far as this is concerned, the patent we are talking about and the application for the patent, can you confirm that Professor Walker-Smith had nothing to do with this patent or any company formed to exploit the intellectual property rights in the substance?
A That is correct.

Q You have told the Panel that Dr 10 was a microbiologist and someone who had made himself familiar with measles virus specific dialyzable lymphocyte extract transfer factor.
A Yes.

Q Again, you have told the Panel that he had become something of an expert in his own right on that because he had done research as well.
A Correct.

Q He had, you have told us, developed a specific interest in this area, and, again, you have told the Panel that in due course a company was set up in which he was to perform an executive role and you a scientific one but in relation to getting the trial on its feet, is that correct?
A Correct.

Q When did you and Dr 10 team up, as it were?
A In the absence of specific documents I cannot answer that, I do not know.

Q Would it have been before the application for the patent?
A I do not know, I just do not know.

Q As far as the company was concerned, the whole purpose was to get funding in order to do a clinical trial ---
A That is correct, yes.

Q --- which had been denied you by the medical school and there was no other pharmaceutical interest in it.
A That was the remaining option that they had recommended to me, yes.

Q Can we go back to the patent application at page 485? It is not headed but it is clearly part of the application, or the description, that deals with safety, is it not?
A Correct.

Q Mr Coonan took you to this last week, page 485:

“Further DLE-TF is remarkably free from adverse side effects. Given intramuscularly or subcutaneously an injection may cause pain at the injection site for 10 to 20 minutes and low-grade transient pyrexia may occur but no other significant problems have occurred. However, severe pain can be induced at the site of primary or metastic lesions caused by tumour necrosis when used in cancer therapy.”

Just look at that, that is two separate points, the first is it can cause localised pain if given by injection either IV or IM.
A Correct.

Q But if it is used in relation to cancer lesions then there may be a different type of localised pain related to tumour necrosis and the lesion itself.
A Correct, yes.

Q So the second part would not concern you if you were dealing with children or with the condition that you have described?
A In both parts in fact, one because clearly we intended to give it as an oral preparation, and, the second, it is not an indication for cancer.

Q Although you said that this was drafted by your patent attorney it was clearly based upon your own scientific research and what you had found?
A That is correct.

MR MILLER: Would you go to D2, the bundle of documents to which you have referred during your evidence? Sir, I know Mr Sheldon has been working on an index to this document, perhaps I do not need it but what I am asking to look at is behind tab 16.

THE CHAIRMAN: Yes, I think Mr Coonan mentioned that Mr Sheldon was working on this and that at some stage we would be provided with a new index.

MR COONAN: I am more than happy to distribute them now. Mr Sheldon tells me they are accurate. They hot off the press, if you would like to have them now they are available.

THE CHAIRMAN: Miss Smith, do you wish to check it first or are you happy for this to be circulated.

MISS SMITH: No, I think I can trust Mr Sheldon.

THE CHAIRMAN: Thank you, I think it would be helpful if it is circulated now. (Same handed) Mr Coonan, can I check with you, the previous index only went up to tab 6, so we will remove that and substitute the new one.

MR COONAN: Yes.

MR MILLER: (To the witness) Dr Wakefield, behind tab 16 there is a document which has two functions, the first is the first page which has dates generated by the computer, it is a print off the screen I think, which indicates that it was last printed, I imagine, at 15.19 on 7 November 1997.
A That is correct.

Q That is the purpose of that document ---
A Absolutely, yes.

Q --- so you can get a time when it would have been – it may have been accessed before that but that is the last time it was printed.
A That is right.

Q The document itself, which follows, is a clinical research protocol and this clinical research protocol was for a proposed clinical trial of transfer factor.
A Correct.

Q If we look at page 22, this time there is a heading in the middle of the page “Adverse events associated with the use of DLE-TF” and if we look at what is written there:

“DLE-TF is virtually free from adverse side effects (reviewed by Fudenberg & Pizza)” – and the reference is given at the end of the document – “When given intramuscularly or subcutaneously, it may cause pain at the injection site for 10-20 minutes. Transient low-grade pyrexia may occur, but there have been no reports of either hypersensitivity reactions or of long-term adverse effects. Patients with either osteosarcoma or breast cancer with bone metastases treated with, and responding to, DLE containing TF of appropriate specificity have experienced severe pain at the site of primary or metastatic lesions, caused by necrosis of the tumour, whereas DLE devoid of TF of corresponding specificity caused neither pain nor therapeutic effect.”

The first part is certainly remarkably close to what was in the patent application and the second part is fleshing out, if you like, the effects when given for the treatment of cancer, pointing out that there is no pain but also no therapeutic effect without the transfer factors.
A Correct, yes.

Q You did write this.
A Yes, this will be almost an exact replication perhaps of what Fudenberg & Pizza have themselves said but put together following my appraisal of safety by reading of the full scientific patent.

Q To the extent that the first part is so similar to what we have looked at in the patent, one can see your input into the safety aspect of the patent application as well as to the application for what was going to be ethics committee approval.
A Correct.

Q In fact, on that point you drafted the clinical research protocol which this document is.
A Yes.

Q Just as you confirmed, it all arose out of your in-depth review of the scientific literature which would have allowed you, first of all, to go into the detail about how transfer factor works, which is what previous pages are about, is it not?
A That is correct.

Q And also to make the confident statement that you have about adverse events and side effects, which we have seen on page 22.
A Correct.

Q Just from the point of view of timing, although this is not in fact the document which was placed before the ethics committee when application for approval was made sometime later, it is a starting point, is it not, and shows the way that you were thinking in November 1997?
A Yes.

Q If you look at the protocol which was before the ethics committee, I think it is in FTP2 at page 676, it was dated 30 January 1998, do you have that?
A Yes.

Q This is an application for approval, or where it starts, and the clinical research protocol for that application follows that, and if you look at page 691 that is where it starts. Perhaps you would accept from me that in fact it has the same “Adverse events associated with the use of DLE-TF” as we had in the previous document?
A Correct.

Q As you have told the Panel, you discussed the safety aspects of transfer factor with Professor Walker-Smith and, as you said in evidence, reassured him presumably upon the basis of your understanding of the scientific literature.
A That is correct.

Q And you reassured him that it was safe.
A Yes.

Q We will come back in a moment to the precise circumstances in which that advice was given, but can we move forward from the application from January 1998, which is just before the publication of The Lancet paper. Everything has been put together for a proposed clinical trial, and it was hoped that that was going to be something which would go ahead, funded from whatever source?
A Yes.

Q I think various things had to be done, which Professor Walker-Smith will tell the Panel about, ethical approval was finally given by Dr Pegg’s committee on 18 December 1998, and I think we have that at FTP3, page 971. It is really taking us to the end, 18 December 1998, from Dr Pegg, giving you permission to proceed with the trial?
A Correct.

Q While giving Professor Walker-Smith permission to proceed with the trial.
A Correct.

Q Can you just in a few sentences work out what happened to it, because we do not find it went ahead and we have seen that Professor Zuckerman was not keen for the medical school funds to be made available for it. Again, we went through the correspondence both with you and Professor Zuckerman. Did the trial ever go ahead?
A No.

Q As you have said, you were given advice to set up a company to get venture capital to support the trial, but that never in fact occurred. Is that right?
A No.

Q At some stage was it thought that lottery funding might be available for it?
A Yes. We put in a huge application to the National Lottery Board, which was unsuccessful.

Q When was that?
A I am afraid I do not remember.

Q I think it is a good deal after 1998. I think it is this century some time.
A We tried hard to get this going but it foundered.

MR MILLER: Sir, I should have given you the reference. I likely said that that the clinical and scientific protocol in the application had the same adverse events associated with it as the one we looked at in detail. I did not give you the reference for that, but for the purposes of your note it is at FTP2, page 698. I did not take you to it because it is in the same form as the last one we looked at and you have now looked at it twice. Sir, I have some more that I have to deal with which will take me probably more than five minutes. Perhaps this would be an appropriate time to break.

THE CHAIRMAN: Okay. It is 11 o’clock. We will now adjourn and resume at twenty minutes past eleven. Dr Wakefield, you are still in the middle of giving evidence.

(The Panel adjourned for a short time)

THE CHAIRMAN: Mr Miller.

MR MILLER: Thank you, sir. The last topic I would like to deal with, Dr Wakefield, is the case of child 10. This is going to involve going through some of the documents, but not very many. It involves having available to you FTP2, which I think you probably still have there, and also if it can be to hand but not immediately available, the medical records of Child 10, which are general practice records, and there are two Royal Free records. Please have them nearby, but we will start with FTP2.

During your evidence, Dr Wakefield, the Panel was shown two letters. The first is at FTP2 at 494a, and the second is in the same bundle at 607a. I do not think you had retained copies of either of these letters, had you?
A No.

Q The sequence, as we may remember was, I think you were given the second of the letters – we call it the ‘Lloyd’ letter – by Professor Walker-Smith’s legal team and, later on in these proceedings, you were given this letter here in the form in which we have it now?
A Correct.

Q If we look first at 494a. The date is important. It is 23 July 1997. We can take it, although it is not clear, that it was addressed to Wendy Spicer, but whatever her name is, it is addressed to the Dispensary Manager. If we put a time on this, it would have been after the filing of the patent application, which was in early June – 5 or 6 June – so we can take it that by the time this letter was written you had done all of your safety research by the date of this letter that was written to the dispensary manager?
A Correct.

Q Although it is signed by Professor Walker-Smith and you, I think it is fair and it is pretty obvious that it was written by you because we can see that it goes out from the Academic Department of Medicine, which is your department . The reference on it is AJW/NK. “NK” is your secretary, is it not – or was at the time?
A That is correct.

Q The middle paragraph of that letter on page 494a plainly embodies your thinking about the transfer factor itself. It is distilled down, for the purposes of Wendy Spicer, but it contains a brief description of it?
A That is correct.

Q You actually had the transfer factor at the time, you told us, having been given it personally by Professor Fudenberg. If we look over the page at 494b, the last paragraph:

“The supplies of the drug are presently in our hands (Dr Wakefield) and will be deposited.”

Then, if we just look at the pages that follow, 494c-d, under the heading “Transfer Factors in Measles”, can we take it that that sets out the most relevant scientific studies on efficacy and safety that were available at the time?
A These are references specifically on measles virus. They may not necessarily be the most comprehensive references on safety, but they refer specifically to the indication to measles virus.

Q As you already confirmed this morning, your researches into safety had been sufficiently comprehensive for the statement to have been made in the patent application which is followed through in later applications for ethics committee approval?
A I was very happy with the safety profile.

Q And you have confirmed that you discussed the questions of efficacy and safety with Professor Walker-Smith before this letter was written and had satisfied him that transfer factor from this source was safe?
A That is correct.

Q The second letter, dated 15 September is at page 607a, from Dr Lloyd, who was the Chairman of the Medical Advisory Committee. It is addressed to you, although a copy of it goes to three other people, the third of which is Professor Walker-Smith. Do you have the page? It is actually written to you but copied to ---Who is Mr John Farrell? Do you know that?
A I believe he was one of the senior staff in the dispensary.

Q And it says, “Mr Steve Tomlin – Pharmacy”. Those two are the first two to whom it is copied, and then Professor Walker-Smith. It is clear that you had written a letter and, by implication, you alone, on 9 September 1997. I say that because Dr Lloyd in this letter appears to make a distinction between your letter of 9 September 1997 and your joint letter with Professor Walker-Smith dated 23 July 1997. So it looks as though it was your letter of 9 September, and you alone. Do you recollect what that letter was about, the one of 9 September 1997?
A It will have been a more detailed appraisal of transfer factor, its efficacy and safety profile, and will have discussed the preliminary approach of the parent requesting this treatment and the circumstances in which it would be given and monitored, I would imagine.

Q It looks as though it would have addressed the question of your intention to conduct an open label study because – and I will be corrected if I am wrong – I do not think the original July letter actually referred to that. If you look at the seventh line of this letter, Dr Lloyd says:

“I note that you intend to conduct an open study of this therapy; you should seek approval from the Ethical Practices Committee before you embark on the study.”

So if it is not in the first letter, it must have been in the second letter?
A Correct.

Q And this letter gave you Chairman’s approval on a named patient basis to use transfer factor for Child 10. As you have implied, Dr Wakefield, when you dealt with this, in the normal course of events the treating doctor would be expected to make an appointment with the parents and explain the purpose of giving the drug. When you give your evidence you said Professor Walker-Smith will have, or would have, made an appointment to see the parents to discuss giving the drug. That is what you would expect in the normal course of events?
A That is correct.

Q And the drug would be prescribed by the doctor and, on that prescription being transmitted to the pharmacy, the pharmacy would dispense the medicine and that is the way in which it works within the hospital?
A That is correct, yes.

Q You would expect, would you not, a paper trail to show that happening, particularly from the pharmacy and particularly with a novel preparation?
A Yes, you would.

Q However slapdash – that is not meant to be pejorative – but however careless a doctor might be about including everything in a note, in terms of the pharmacy’s dealings – dealing with drugs, in some cases dangerous drugs, not this one but in some cases dangerous drugs – there is a high expectation that the documentation will be correct, is there not? You are nodding your head?
A That is correct, yes.

Q My simple point is, pharmacies have to be even more rigorous than doctors?
A Yes, and I think that there is a reference in the letter to Ms Spicer, to the effect that I have handed over the composition, the pharmaceutical composition, and that she has ticked off various elements that would be of concern to her, to make sure that the dose, the storage and other aspects are correct.

Q Shall we just look at that. It is page 494b, the last paragraph.

“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.”

So at the time the letter was written, it had not been deposited, but somebody has written – whoever it may be – the notes in handwriting at the bottom of the page which have various questions on them, which somebody may or may not be able to deal with. What was being said in the letter was that it was in your hands and it was going to be deposited with the pharmacy. Just help about this, would you? You are more familiar with the medical notes than we are, not least because you had them, obviously, in 1997 when the paper was being produced, so you have actually been through all these notes. Do we have any record in the Royal Free notes that this drug or substance was dispensed by the pharmacy?
A I do not believe there is, no.

Q Can we just look at the clinical notes. Put FTP2 on one side, would you. The relevant records are the GP records; then there is Royal Free 1 and 2. Would you turn to page 65 of the general practice records? This is a letter which we have looked at already earlier in the proceedings and then when you gave your evidence. It is from the community paediatrician, Dr Davis, to Dr Thomas who I think is a general practitioner. It says:

“I saw 10 today [for which we can read 5 August 1997 because that is the day of the clinic] with his parents. They were very saddened that he had quite a developmental regression all of a sudden this summer.”

Then the last sentence of that first paragraph:

“He is on Salazopyrin for bowel inflammation and is awaiting some new treatment with measles transfer factor.”

If this is 5 August, Dr Wakefield, this would be before any permission had been given by the Royal Free, is that right?
A That is correct; this is not my letter of course.

Q I appreciate that, but I am just trying to put it in its context because we know that the permission that was given was given in October by Dr Lloyd so this is the community paediatrician talking about a new treatment with measles transfer factor, but he is writing on 7 August about a clinic meeting with the parents on the 5th. We have seen no correspondence in any of the notes between the Royal Free and Dr Davis about measles transfer factor so may we take it that the source of this information probably is from Dr and Mrs 10, that they are telling Dr Davis.
A That is my assumption, yes.

Q I said October but it is in fact September that the permission comes through. The permission comes through to you on 15 September 1997 and so we need to look for an outpatient clinic appointment following that date, which you said is what you would expect, or even a letter from one of the clinicians up at the Royal Free indicating that there has been a meeting, a discussion presumably, and then a prescription by whichever doctor may have seen the parents. If we could just look at the Royal Free notes volume 1, please, again you are probably more familiar with these notes than I am, but is there any reference in the Royal Free notes to any outpatient appointment in the paediatric gastroenterology department in September, October, November 1997 or any letter that you have seen from Professor Walker-Smith to the parents about this?
A I have not seen such a letter but I am not so familiar with the records that I would be able to …

Q Again, I am sure, Dr Wakefield, that if we find something – I have been through the records and I cannot find anything – then of course it will be unearthed and the Panel will know about it. If you look at RFH2, please, at page 19, the date has been cut off mine but we can see that it is October 1997; do you have that?
A 23 October 1997.

Q So 23 October 1997, SHM is Dr Murch is it not?
A Correct.

Q It is in his handwriting and it does not look, on the face of it, like an outpatient clinic note, does it?
A It certainly does not have a stamp.

Q If you look at it it refers to AXR, an abdominal x-ray, I think it says “rectal distension. For treatment with liquid paraffin, 20 mls daily, alternate days”, is that right?
A Correct.

Q Then it goes on to deal with some aspects of the family history and the autoimmune status of the child, but it certainly is not a prescription for transfer factor, is it?
A No.

Q Then – I am sorry to make you do this but it is the last time – if we go back to RFH1 at page 24, do you have that?
A A fax cover sheet, is that correct?

Q Yes. It is a fax cover sheet from the secretary to Dr Jenkins who was the local paediatric gastroenterologist in South Wales and it is a fax to Sister Jill Thomas, your research nurse, dated 26 November 1997. In the text at the bottom of the page it says:

“Mrs 10 is anxious to start 10 on his new medication and said if I faxed you the result of his recent abdominal x-ray you would be able to ring her and give her the go-ahead or not to start the medication, is this right? Anyway, please find the abdominal x-ray result as enclosed.”

Then the following page is a copy of an x-ray request and report and the top part of it is the request.
A Yes.

Q It looks as though this is Dr Jenkins, dated 19 November 1997, and in the big box under “Clinical information” it says:

“Inflammatory bowel disease and autism. Under the paediatric GI/IBD unit at Royal Free Hospital, London and my request for abdominal x-ray [question mark] no faecal loading prior to new treatment.”

That is what accompanies the fax cover sheet. Certainly one reading, Dr Wakefield, of Mr Jenkins’ secretary’s note on the fax cover sheet is that Mrs 10 already has the new medication and what she needs is the go-ahead or not to start it, would that be fair? Just turn back if you would to page 24.
A Yes, one might read that into it. It does not fit with the fact that by this stage I have clearly agreed to provide it to pharmacy and pharmacy appear to have received it and ticked off what they felt were the relevant concerns. I am afraid these are not my documents.

Q I know that, but I think you need to deal with them – in fairness to you I think you need to deal with them. Again, there is a document in that same bundle which we looked at earlier during your evidence. If you go right to the back of the bundle at page 181, this is part of a diary and I think you told us that this is something that was being collated by Jill Thomas, that she would have been receiving this information from mothers or fathers, describing how their children were from time to time with a view to future trials.
A That is correct.

Q We see at the bottom of the page, just about seven lines up:

“He is not as good as he has been recently. Over Christmas and New Year [1998] we felt very optimistic about the apparent effect of transfer factor, there seemed to be such a noticeable change in 10, but this week we feel pessimistic.”

THE CHAIRMAN: Again, for the members of the press sitting in the gallery, if by mistake the name of any of the children is divulged, please make sure that the name is not published.

MR MILLER: Thank you, sir. Certainly if one takes that at face value it looks as though certainly by Christmas and New Year the child was receiving the drug and was apparently responding to it.
A Correct.

Q Dr Wakefield, Professor Walker-Smith will tell the Panel that he neither prescribed nor administered the transfer factor to this child and, to his knowledge anyway, none of the doctors in his department did either – I just tell you that that will be his evidence – and the documentation that we have been through certainly does not suggest that any of them did prescribe or administer the drug, does it?
A No.

Q If they did then it is not documented at all, which would not only be unusual but highly irregular, would it not, with a novel drug?
A Unless the pharmacist had taken those instructions that were given to her or him and decided to act on that basis. I have no experience at all with how novel drugs are handled, this is not something with which I have dealt before so I cannot tell you the precise mechanism by which this would happen, but it does seem unusual, yes.

Q There would be no need for irregularity in this case because, as we have seen, Dr Lloyd had given permission for this patient to receive that drug.
A Absolutely.

Q I am sure, Dr Wakefield, that you would not wish for Professor Walker-Smith to be found responsible for something which he did not do.
A Absolutely.

Q Can I ask you two final things then? Is there any way that Dr 10, the child’s father, could have got hold of the transfer factor? He was, after all, very close to the action.
A Yes, there is. It could have been purchased directly from Dr Fudenberg since it was available over the counter in effect. It could be obtained directly and it was my understanding that to do that one had to have an appointment with Dr Fudenberg, and that clearly was very expensive because it involved going to South Carolina. Nonetheless, it may well have been obtained in that way. The other alternative is that it was provided by me except for the fact that I have already ----

Q You have anticipated my last question, Dr Wakefield: did you give Dr 10 or Mrs 10 the transfer factor which you had got from Professor Fudenberg which was going to be placed in the pharmacy?
A It seems illogical; I seem to have already placed it in the hands of pharmacy who have done a check against the details with which I provided them, so that does not fit with the facts as they are documented in the records.

Q We may or may not hear about what the handwritten annotations on that letter mean, but you are basing this on the handwritten annotations on that letter, are you?
A Not unreasonably, yes, I think.

MR MILLER: Thank you, Dr Wakefield.

THE CHAIRMAN: Dr Wakefield, Mr Hopkins now on behalf of Professor Murch will be cross-questioning you. Mr Hopkins

Cross-examined by MR HOPKINS

Q Good morning, Dr Wakefield. Can I just begin with a few preliminary observations so you understand the direction in which I am approaching my questions of you? Clearly, we are dealing with events some 10 or 12 years ago and inevitably there will be differences of recollection over such a distance in time, particularly so when one is dealing with events that are undocumented, so some of the questions that I am about to put to you are based on some differences in recollection between you and Professor Murch, but it is in that spirit and to seek clarification that I put those questions to you. Can I then start with the topic of the development of the protocol, and on behalf of Professor Walker-Smith some of this ground has been covered already so I will take things fairly shortly if I may.

As I understand your evidence parents started contacting you following the publication of a 1995 paper dealing with bowel problems and Crohn’s disease that attracted media attention, is that right?
A Correct.

Q You listened to the histories that those parents gave, not only of their bowel problems but also behavioural problems that some of them had.
A That is correct, yes.

Q Some of those children, as you have told us, in fact had been diagnosed as being placed on the autistic spectrum.
A Yes.

Q If I understand your evidence correctly, you advised those parents that if they so wished they should contact their GPs to consider referral to Professor Walker-Smith and his team.
A Over time, yes.

Q Again, if I understand your evidence correctly you kept Professor Walker-Smith in the loop about possible referrals that may come to him for clinical investigation.
A That was my understanding, yes.

Q Turning to the motivation of the parents who contacted you, particularly focusing on the Lancet 12, would it be right to say that without exception they were all highly motivated?
A Yes, they were.

Q In particular, they wanted to rule in or rule out potentially treatable causes of their children’s problems.
A That is correct.

Q Would it be fair to say that the parents of the Lancet 12 knew about the colonoscopy procedure before the child first attended at the Royal Free?
A Yes, and this came about because the parent network was really quite sophisticated by that stage and they were aware that gastrointestinal investigation involved that sort of procedure.

Q This was perceived to be a means of investigating the bowel problems that their children had and that they were reporting.
A Yes.

Q Can I then deal with outpatient assessments. We know in respect of The Lancet that Professor Walker-Smith saw nine of those children in outpatients; the two he did not see were children 4 and 8 and we just do not know about child 11, the XXX child, would that be fair?
A Correct.

Q From what you have told us you, on some of those occasions if not all, sat in as an observer at the outpatient assessments.
A Yes, I did.

Q Just having set that background, would it be right to say that when there were discussions about the clinical protocol of investigations, the information available to help formulate that protocol came from histories that had been given to you by the parents before they were referred and histories that Professor Walker-Smith had obtained in outpatients.
A Yes, I think that is a fair comment.

Q Those histories were shared in general terms with other members of the paediatric gastroenterology team, including Dr Thomson and Dr Murch, as he then was.
A Yes. I think the multidisciplinary emphasis was that the history was described and the relevant experts were recruited in an effort to help interpret those histories.

Q So apart from the paediatric gastroenterology team, this information was also being shared with, in particular, Dr Harvey for neurological advice …
A Correct.

Q And Dr Berelowitz for psychiatric advice.
A That is correct.

Q Therefore, it was these histories that provided the basis for the development of the clinical protocol.
A Yes.

Q I think you have told us that there were common themes in those histories, particularly a normal development of the child and then regression with loss of acquired skills, such as speech, play and interaction.
A Correct.

Q Another common theme was gastrointestinal problems such as diarrhoea or intractable constipation, pain, sometimes blood and mucus, sometimes a failure to thrive in comparison with siblings.
A Correct.

Q Also in some of the cases there was a pre-existing diagnosis of the child being somewhere on the autistic spectrum?
A That is correct.

Q Turning to the timescale for the development of that clinical protocol, you have been questioned by Mr Miller about this, and I do not intend to repeat it, I adopt the questions that he put to you on this, but can I put to you Professor Murch’s recollection of the timescale? He does not recall being involved in deliberations about that clinical protocol until about April 1996: do you accept that that is a possibility?
A It is certainly a possibility. The only precise date that I have is the one in the document.

Q I understand, I need not go over that; you have been questioned about that already. In any event, I think it is common ground amongst us, that certainly by the summer of 1996 the protocol of clinical investigations had been developed for the assessment of these children.
A Yes, I think the meeting that was called for April, clearly by virtue of the document that was introduced by Mr Miller this morning, talks of collaborators, talks of an established entity coming together in April, and asking for costings. Now, costings are something that really come at the every end of the establishing of a protocol where you are putting the fine details on what it will cost the individual collaborator for their element of the test, so this is really, as I would see it, the culmination of a series of meetings or discussions on this and I cannot say precisely which collaborators had contributed to that existing state of affairs by April but I certainly would imagine that the senior collaborators, Dr Murch, Dr Thomson, Professor Walker-Smith and others, would have been involved by that stage.

Q I put to you that Professor Murch’s recollection is that it was in April 1996 when he recalls first being involved in the development of the clinical protocol.
A All right.

Q A separate matter: Child 4, and for this you will need the GP records and the Royal Free records: just to remind ourselves of the chronology in respect of Child 4, looking at D8, which is the table that was introduced at the start of your evidence, we see that on 1 July 1996 there was a referral by Child 4’s GP, and if we go down to 29 September 1996 we see that is the date when Child 4 was admitted to hospital. Going back to the evidence that you have given about this, I understand you to be saying that before that child’s admission to hospital you had had some telephone contact with Child 4’s parents, is that right?
A Sorry, I am just trying to remember Child 4. Yes, I think that is right, correct.

Q I will be taking you to a letter in respect of Child 4 now, so if you turn to page 125 we see, do we not, a letter in type that you wrote to the GP dated 12 June 1996?
A This was a letter to [Mr 4] from me.

Q Child 4’s father, yes, and I think you have indicated that this sets out that there was communication between you and Mr 4 in respect of this child?
A That is correct.

Q As I understand it you also had, or accept you must have had, a telephone discussion with the GP about Child 4.
A Yes.

Q When you were asked questions by Mr Coonan about this I think you accepted that because we see this letter in the GP records, and we see the handwriting on it, that these were probably the GP’s annotations relating to that telephone conversation?
A I believe that is correct, yes.

Q In looking at those annotations it is clear, is it not, that you were providing this GP with background information that you had so the GP could put the whole thing in context?
A That is correct.

Q We see that the GP has, in the left hand margin, made annotations “Blood tests, history, 1 week in hospital” then an arrow, “underlying problem, treatment to help diarrhoea – weight loss and autism”. Would it be fair to say that those matters recorded by the GP would have been matters that you would have specifically been discussing with him?
A That is correct, yes.

Q In particular, when there is the reference to “underlying problem”, do you think that would have been relating to an investigation of the underlying problem during the hospital admission, because if you see it is then followed with “treatment to help”?
A Yes, I think what it is saying is that in response to the question “What might this involve? What is the purpose of this?” It would have described a series of investigations that might be undertaken, such as colonoscopy, in order to elucidate if there was an underlying problem, such as bowel inflammation.

Q Where it goes on to say “Treatment to help”, was the hope that these investigations would result in some diagnosis that may be amenable to treatment?
A That is exactly right, yes.

Q We see here a reference to diarrhoea, weight loss and autism: can we take it from that that these were features specifically relating to Child 4 that were being discussed?
A I believe that is the case, weight loss was a particular problem in this child so I believe that is the reference, yes.

Q If we then move on to see the referral letter, if we now go to the Royal Free bundle at page 27, the Panel has been through this many times, I need not trouble with the detail of it because it is familiar to us all now, but we see this letter was dated 1 July 1996 from the GP, addressed to yourself, purporting to make a referral to you.
A That is correct, despite the fact that the annotation of John Walker-Smith was in his letter, or on the letter.

Q You have explained how that confusion may well have arisen, and that is not the purpose of my question, because we see on the preceding page, page 26, your document of 4 July 1996, passing on this referral to the correct quarter to Professor Walker-Smith, making a reference to Child 4.
A Correct.

Q Presumably the reason that you passed this on to Professor Walker-Smith was because it was his decision whether or not this child should be accepted by way of referral and/or admitted for clinical investigation.
A That is correct.

Q We know there is some handwriting on here “TCI”, would that normally be an abbreviation for “to come in”?
A I think so.

Q Then “What for?” There is a date, 1 August 1996, and then “poss endoscopy” and then “done 10.7.96”. Are you able to cast any light on whose annotations those would be?
A I am afraid not, no.

Q Professor Murch has a recollection that in respect of at least one of the autistic children coming from the XXX (as we know this child did) the parents were reluctant to bring the child down for an outpatient assessment due to the distance they would have to travel, and the child’s behaviour, simply for an outpatient appointment: does that ring any bells with you?
A Yes, absolutely. I remember in particular this child – there was another mitigating factor and that was the cost. They were very poorly off and the idea of going and coming back and going again and coming back, it was deemed I think that it was better that one trip was made, and I think those were the circumstances that this happened.

Q It is also Professor Murch’s recollection that a view was taken that that child need not be brought down, or there was no insistence for an outpatient assessment, but a history was ascertained over the phone: does that ring any bells with you?
A I do not remember that. By this stage it had been moved on to Professor Walker-Smith’s domain.

Q From the information that you had obtained about this child, from what you were being told, did you understand that this child had significant gastrointestinal symptoms?
A Yes.

Q Presumably you would have passed on what information you had about this child to the paediatric gastroenterology team, would that be fair?
A It may well be that … It is difficult, I only have the documentary evidence in front of me so … I have no memory of that but Professor Walker-Smith may have asked if what I had understood was corroborated by the GP’s letter but I simply do not remember.

Q We can move away now from Child 4 and go on to file FTP1, pages 212-225. At pages 212-225 we have the paper that is entitled “Proposed clinical and scientific study”, is that right?
A Correct.

Q You have told us that you drafted this paper and it subsequently formed part of the 172/96 application, which commences at page 200 in this bundle.
A That is correct.

Q I want to deal first of all with the timescale of the circulation of this paper starting at page 212. It is Professor Murch’s recollection that the first time he saw this would have been in July 1996 on his return from a holiday, is that something you would accept or is that a possibility?
A Can I just refer back to the document introduced by Professor Walker-Smith this morning?

Q Certainly, it is at page 93A in the bundle. Is this the document you mean?
A The handwritten note, yes. As I said, this meeting will have been convened at what is a relatively advanced stage when specific costings were being requested so it would be likely that this document, minus the costings, would have been ready at this stage.

Q Can I just pursue that a little with you? It would appear that the purpose of that meeting was to help draw up or finalise a clinical protocol and if we turn on to page 221 in this paper we see the start of the list of investigations that were intended to be carried out. What I am suggesting to you is that this paper had been circulated after the clinical protocol had been drawn up. I am not suggesting that you yourself would have started working on it, but the first time that Professor Murch recalls seeing it would have been in July of 1996.
A I am not going to dispute that at all. I mean, if that is Dr Murch’s memory then I have nothing other than these documents – or no reason otherwise to dispute that.

Q Leaving aside the timescale now, if we look at what was contained about coordinating investigators in this document, on page 212, halfway down, we see that you are described as the coordinating investigator.
A That is correct, yes.

Q Then, if we turn the page, we then see the investigators in terms of departments and we see that Dr Murch, as he then was, towards the top of the page, about the fourth line down, has been described as the coordinating investigator in respect of that department. Are you aware that when Dr Murch first saw this document he objected to this proposed role, and took up his objection with Professor Walker-Smith, simply on the basis that he was just over-stretched and that he did not want to take on the burden that was envisaged here. Was that objection passed on to you, or notified to you in any way?
A I do not remember it, and if it had have been, this document was open for anyone to make corrections. That really is as far as I can take it.

Q Moving on to the decision to seek ethical approval for 172/96, I think you accept this proposition: that from Professor Walker-Smith’s standpoint, and the standpoint of his team in the middle of 1996, they themselves saw no need for an ethics application because all the investigations they wished to carry out in the clinical protocol were based on clinical need. Would that be fair?
A That is correct. As I have said, the additional investigations, the adjunct scientific investigations such as vitamin B12, metabolism and such as the complement genetics were entirely research, and they were the additional elements that required ethical approval.

Q Can I then move on to the discussions around the 172/96 application form which starts at page 200. Can we go back to the start of that, please? I want first of all again just to deal with timescale. Do you recall that when this was in draft there was a meeting in which acetate sheets of the draft were presented by you to various members of that meeting?
A I do not remember the meeting. It may well have taken place. I know this issue was raised some time during the last session, and I am perfectly willing to accept that in line with the interaction that we had in the drafting of this document that that meeting took place.

Q I want to deal with the timing of that meeting before I move on to the contents of that meeting. In terms of the timing, Professor Murch recalls seeing the draft for the ethical application form that starts at page 200 in September 1996. That is the first time he recalls seeing it – shortly before a Thursday meeting of the paediatric gastroenterology department. Do you accept that that is a possibility?
A I cannot help you in terms of precise timing. Is it a possibility? Of course.

Q And in terms of people present – and, again, I think you understand that I have to put most things to you to give you an opportunity to comment ---
A Of course.

Q --- even if you have no specific recollection. The people who were present at that meeting, apart from yourself and Dr Murch, Professor Walker-Smith, Dr Thomson, Dr Casson, possibly Dr Phillips and possibly others?
A Again, I do not remember it but I am perfectly willing to accept that.

Q Whether or not it was at that meeting – this is certainly Professor Murch’s recollection – but at one of the meetings that took place in respect of this the rationale for various investigations was debated backwards and forwards?
A That was a continuous process, right, at our various meetings. Yes.

Q And as part of the debate which Professor Murch thinks was at this particular meeting, Dr Thomson advocated lumbar punctures because he thought it necessary to exclude mitochondrial disorders?
A That I do remember, yes.

Q And furthermore, I think as you told us already, he had experience of lumbar punctures being part of a protocol in the Birmingham Hospital from which he had come, where it had been used to exclude metabolic disorders?
A And indeed, he introduced us to that protocol, yes.

Q I do not think we need go into it. We have seen it only recently. It is in Child 2’s notes. Just for the Panel’s footnotes, it is RF 315-352. (To the witness) What I am going to suggest to you next, Dr Wakefield, is this. When this draft application was being discussed – turn to page 201, about two-thirds of the way down – you see the reference to lumbar puncture and it says:

“… for measurement of CSF antibody and cytokine profiles.”

When this application form was being discussed before it was submitted, the clinicians, particularly Dr Thomson and Dr Murch, as he then was, were saying that the primary clinical aim from their perspective was to exclude metabolic disorder?
A It was certainly one of the main clinical aims, yes. There were to be general examinations of the cerebrospinal fluid as are routine, such as bacteriology, such as microscopy. Again, in accordance with the Birmingham protocol there was a viral antibody analysis.

Q Indeed. I fully accept that there were other clinical indications for it, but what I am suggesting is that what was being put forward by the clinicians when they were reviewing this draft was the primary purpose. It was to exclude a metabolic disorder. Professor Murch recalls that you actually annotated an acetate sheet to this effect?
A May well be the case.

Q Thank you. May we now move on then, further on in time, to the cessation of some of clinical investigations that happened at the beginning of 1997. If you just turn up, please, pages 366aa and b. They are on green paper in this bundle. Here we see a letter that you have been asked about before. You write in 3 February 1997 to Dr Pegg and, in the second paragraph, on 366aa, you make reference to the pilot study which –

“… has demonstrated that the MRI and EEG studies are all normal and therefore we feel there is no need to continue these unless specifically indicated.”

I just want to come back to the reason these were stopped. Is it right that from the clinicians’ perspective, the experience they had had to this point was that these tests were revealing nothing useful by way of clinical information that might influence the management of the children?
A That is absolutely correct, yes.

Q And it was for this reason that they said that these investigations should now drop off the clinical protocol?
A Correct.

Q You quite correctly then were informing Dr Pegg that they should play no part in the 172/96 application that had been made because the clinical justification had now gone?
A That is correct. He had requested that any changes – any – should be made known to him, and that is, we were acting in the spirit of that request.

Q I want to then turn to the cessation of lumbar punctures on patients, which is really covering a similar theme. Can I just lay the background, please. Can we go back to D8, to remind ourselves about the timetable in respect of Child 7. You have a mass of papers there. If I read it out, I do not think you yourself need look at it, but this is just so the Panel knows where it is. The referral of Child 7 was on 5 December 1996. The outpatient appointment was on 15 January 1997, the child was admitted on 26 January 1997 and investigated over the next few days until 30 January 1997. In respect of Child 7, were you aware that at some point in February Dr Berelowitz was advising that this child did not have a disintegrative disorder or a condition similar to it?
A These are the documents that Dr Berelowitz submitted somewhat later on – is that right?

Q Certainly written documents later on, but I am talking about now orally telling people.
A I have no memory, I am afraid.

Q Let me just set the background so that you are then in a position to comment. That in turn was communicated to the clinicians including Dr Thomson and Dr Murch (as he then was), and resulted in discussions in their department and Dr Thomson and Dr Murch reached the view that lumbar punctures should no longer be carried out as part of the clinical protocol unless there was a sufficient history of regression to create the clinical need to exclude a metabolic disorder. Do you remember that issue surfacing in February 1997?
A Yes, I do, just as with the dropping of the MRI and EEG, the clinicians took the view that lumbar puncture was no longer merited on clinical grounds because it was not yielding any useful information and it was discontinued.

Q And you accepted this as a clinical decision?
A Absolutely.

Q Thank you. You can then put away D8 and let me now move on to the issues relating to The Lancet paper. For that I think you will need FTP2. Before we turn to a specific page in here, let me just again cover a bit of ground to set the scene. You told the Panel that in respect of this paper you were the lead and corresponding author, although obviously you had input from other co-authors, including Dr Murch?
A Yes.

Q You prepared the first draft for The Lancet and all subsequent drafts, and liaised with The Lancet about alterations to the drafts you submitted?
A No. I liaised with colleagues about the drafts, and then dealt with the final draft and The Lancet which, again, when changes were requested, they were made in collaboration with my colleagues, and the final draft with those corrections submitted to The Lancet.

Q I will come back to that. Certainly Dr Murch accepts that the draft that was being circulated in October 1997 – let us just turn up page 616a. It is the green page, and you were taken to this by Mr Miller earlier this morning. We see from this it is dated 8 October 1997, although this is the one that went to Professor Walker-Smith. We can see that you were circulated the draft to all those we see listed there, including Dr Murch?
A Correct.

Q We see that you, as Mr Miller pointed out, described it as the final version of the first Lancet paper on this subject. This particular draft that was being circulated in October 1997 was something that then came under further discussion among the co-authors. Is that right?
A Yes, almost certainly.

Q Indeed, that was the point of this being circulated?
A That is right.

Q Do you recall that Professor Walker-Smith proposed there should be a review of the histology slides for the Lancet 12 so that the pathologists involved could be happy and content with the description that appeared in that draft?
A What I remember, and the final histology was based upon the detailed analysis by Dr Paul Dhillon, and precisely when that was done I cannot say, but I believe that it was done contemporaneously with the analysis of each child; however, it may be that at some point he reviewed his analyses and that may have happened after this. I do not remember that specifically being requested but it is part of the due diligence and it may well have happened.

Q Let me put to you a meeting. I think you probably heard me question Dr Davies about this too, but I have to put it to you.
A Of course.

Q It is Professor Murch’s recollection that in October 1997, following the circulation of the draft that went with this document, that a Friday lunch time meeting was arranged in the histopathology seminar room, with the primary purpose being to look at the Lancet 12 histology and that that meeting was attended by Dr Sue Davies, yourself, Professor Walker-Smith, Dr Murch (as he then was), Dr Andrew Anthony, Dr Thomson, Dr Dhillon, Dr Casson, possibly Dr Heuschkel?
A Again, I have no memory, but I am perfectly willing to accept that that is the case.

Q And then at that meeting a consensus was reached, which included all three histologists, that the histology descriptions in The Lancet were accurate?
A It is certainly my memory that they were deemed accurate by the pathologists, yes.

Q Leave aside whether it is that meeting or not, is it your recollection that the histologists whose names appear as co-authors on The Lancet were in agreement about it?
A Certainly. Absolutely.

Q Aside from the histology, at the end of that meeting there was a further discussion between a smaller group, which included yourself, Professor Walker-Smith, Dr Thomson and Dr Murch (as he then was), about the section on the draft paper relating to ethical approval. Can we just turn to that page – page 764, please. I appreciate you have said to me you do not recall specifically the meeting in the way you approached the question I put to you, but let us now leave aside that meeting. Do you have any recollection of having a discussion with Professor Walker-Smith, Dr Thomson and Professor Murch about this passage that we see in this draft?
A Again, I do not remember details, but I can say for sure that this passage was technically incorrect and required revision, and that is the revision that one finds in the final published document. Again, in my evidence I think I refer to this. In fact, the reference to this clinical investigation, however it came to be, in this draft was in fact incorrect since clinical investigations do not require ethical committee approval.

Q You have anticipated where my questions were going.
A I am sorry.

Q I have to put it to you, so let me just break it down. What I am suggesting is that the discussion between that group of you was, just as you have described, to the effect that the wording we see here was not accurate.
A Absolutely correct, yes.

Q There was also a discussion that what this paper was doing was presenting a case series.
A Correct.

Q Professor Murch recalls you mentioning that you had discussed the wording of this passage with The Lancet; had you done that?
A I have no memory, I am afraid.

Q Is it possible that you had been discussing this with them in an attempt to get it right?
A It is unusual – I suppose historically that clearly by this stage the second paper, the science paper, has been rejected so we are left just dealing with this paper on its own and it may well be that Dr Bignall, who was the sub-editor, may have raised a question in respect of this, but I have no memory of it.

Q Let us just stand back for a moment and see what the situation was with the October 1997 draft. The Lancet paper itself in that draft was describing the results of investigations that had been carried out for clinical purposes in a case series, is that right?
A Correct.

Q Ethical approval had not been needed for the clinically indicated investigations that were reported in it.
A Correct.

Q Including colonoscopy, MRI, EEG and lumbar puncture.
A That is right.

Q There was existing ethical approval, which was 16295, to take extra tissue biopsies at colonoscopy so that research could be carried out on that extra tissue.
A Correct.

Q As we know and as you have told the Panel the phrasing that we see on page 764 was then changed later to the version that we see in the published Lancet.
A Yes.

Q And as I understand your evidence you had input into that changing because you thought the draft as we see at page 764 was wrong.
A Yes.

Q Again, if I understand what you said correctly it was your intention to convey that the research aspects which were adjuncts to the clinical investigation had received ethical approval, and what was going on in your mind was the 16295, is that right?
A Yes, this is a reference to the pro forma-driven analysis conducted by Dr Dhillon.

Q Very well. Finally can I come on to what was circulated after this October 1997 draft? We have seen this morning that in January you wrote to Professor Walker-Smith and Dr Murch to say that they would receive galley proofs within a week or so, but can I suggest that Dr Murch never in fact received one and in fact the last version that he saw of a draft of The Lancet was this October version rather than the final galley proofs?
A Again, I communicated to my colleagues that it would be sent out. It appears that Dr Berelowitz received his copy but again I cannot account for internal post at the Royal Free. If Dr Murch says he did not get it then I accept that.

MR HOPKINS: Dr Wakefield, those are all the questions I have for you, thank you.

THE CHAIRMAN: Thank you, Mr Hopkins. I know we are getting very close to the lunch break but could I first of all ask now the situation as you now see it, Ms Smith?

MS SMITH: Thank you, sir. As far as I am concerned I am going to invite the Panel to give consideration to my beginning my cross-examination of Dr Wakefield tomorrow morning, in other words not sitting this afternoon. I am very conscious of the constraints of time and I am certainly not being profligate with it, but I should underline something that I am sure you are all aware of already, and that is that under the Old Rules under which this case is being conducted whereas every single document that I produce and every oral witness from whom you have heard the defence have many weeks notice in respect of, the same does not apply the other way round. That is not a complaint, it is just the way the system is, so the oral evidence that we hear and the documents that the defence produce are the first that we hear of the defence case.

I hope you will accept from me that cross-examination is shorter if it is structured and it would be helpful to me to have this afternoon in order to analyse the points that have been put this morning by Mr Hopkins and Mr Miller. It also seems to me, sir, that you will find cross-examination the more enlightening the more time you have to remind yourself of the earlier parts of Dr Wakefield’s really exceptionally long evidence-in-chief, and in those circumstances I am going to invite you to use this afternoon as a reading afternoon. I would say – it is a very peripheral matter – that we shall use this afternoon to do a bit of shifting of the room so that I am a bit closer to the witness, because the present situation is not satisfactory, as I pointed out to you at the beginning, when I am actually on my feet with a witness.

THE CHAIRMAN: We anticipated this request coming from you and in fact the Panel was considering that request already. If it is practically not possible for you – and I can see the reasons and I think the Panel can see the reasons for this adjournment this afternoon – we will start the cross-examination tomorrow morning. Obviously, you are going to reposition your furniture in this particular room during this afternoon so it will obviously not be right and proper for the Panel to be present in this room at that particular stage.

MS SMITH: That is right, sir, because in order to bring our table forward – with the defence consent of course – we are going to have to move their tables a bit in that direction so it is rather more elaborate than just shoving this table forward.

THE CHAIRMAN: Again, we all anticipated this request coming from you to a certain extent and, as I have said, the Panel have considered it already and are sympathetic to that particular request.

We will adjourn now for lunch and the Panel will do the reading as appropriate in the afternoon, but for the formal public session we will resume tomorrow morning at 9.30.

Dr Wakefield, you are going to remain under oath and you are still in the middle of giving evidence; therefore, please make sure that you continue to observe that you do not discuss this case with anyone. We will now adjourn, thank you.

The Panel adjourned until 9.30 am on Friday, 11 April 2008

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