Tuesday, February 7, 2012

Day 54 GMC Fitness to Practice hearing for Andrew Wakefield



Friday, 4 April 2008

Regents Place, 350 Euston Road, London NW1 3JN

Chairman: Dr Surendra Kumar, MB BS FRCGP

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

Legal Assessor: Mr Nigel Seed QC


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


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


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.


Page No


Examined by MR COONAN, Continued 2

THE CHAIRMAN: Good morning, everybody. There are some things that are hanging over from yesterday. First of all, the Legal Assessor is going to give some advice about the interruptions that we had yesterday.

THE LEGAL ASSESSOR: Yesterday there was a disturbance from the public area. There had been a similar disturbance earlier in the previous session of the proceedings. I did not feel it necessary to say anything. Yesterday it clearly interrupted the proceedings and that is unfair on the doctors whose cases are being heard. My advice to the Panel is that it is very important that no emphasis should be placed on the behaviour of the people in the public gallery. The three doctors appearing here are not responsible, no matter how it may appear, and cannot be held and should not be held responsible for what happens in the public gallery. Of course members of this Panel may have come to the conclusion it is no accident that apparently an autistic child should appear here during the course of this hearing. The fact that they may come to the conclusion that somebody has engineered that situation cannot be avoided.

The one thing I advise the Panel they must not do is draw any adverse inference against any of the doctors here. What happens in a public gallery and the behaviour of a child, no matter how ill, cannot be evidence in these proceedings. You are specifically concerned with evidence relating to twelve child patients, and you have all the relevant evidence in the papers and will be receiving it. You have heard the case against the doctors and you will be hearing the doctors’ cases. It is purely on that evidence, not on anything that happens in the public gallery, that your ultimate decision must be made.

THE CHAIRMAN: Thank you, Legal Assessor. First of all, Ms Smith, do you have observations on the advice we have just received?

MS SMITH: No, except that I entirely agree with it.


MR COONAN: I agree with it.


MR MILLER: I agree.


MR HOPKINS: I agree.

THE CHAIRMAN: Thank you. The second issue we talked about yesterday was The Lancet papers which we are going to hear evidence about this morning. We talked about whether the Panel would need time before or after the evidence to read those papers. After consideration, the Panel feel that it is better that we start this case this morning and maybe finish earlier today so that the Panel can read the documents at their leisure, either on the premises or outside the premises, because there is nothing confidential about The Lancet paper.

Thirdly, Mr Coonan I know that you felt that it would be helpful for the Panel to be provided with The Lancet papers altogether in one bundle. Ms Smith, I recollect, was not entirely happy with that suggestion. Is that still the case? We are quite happy to go along with whatever you both wish to do.

MS SMITH: Sir, I have now been served with the papers which, in fairness to me, I have not had before. I am entirely in the Panel’s hands. I was not objecting in any way to you seeing them, subject to me seeing myself; I was simply remarking that you all have them somewhere else and you have an awful of paper. You might find it helpful if they are crossed referenced. Other than that, it is entirely a matter for the Panel how they proceed.

THE CHAIRMAN: That is exactly the suggestion I was going to make at this stage. If all of you are happy that we are provided with those papers, and if you could give us the cross references of those page numbers, then it will be helpful. As you quite correctly remarked yesterday, we have either highlighted certain passages in those papers already or we may have written some comments on them.

MR COONAN: Sir, I say again simply to help, the direct numbering from the bundle you have are at the bottom of the documents, so you do not need to do anything.

THE CHAIRMAN: That helps me if that is the case. I expected that might be the case, but not having seen those, I was not quite sure.

MR COONAN: Sir, as a mechanical exercise, it is entirely up to you whether you want that to be done now or whether we distribute that later on. I am in your hands.

THE CHAIRMAN: I would prefer that that they are distributed in that case now, just in case we need to look at them while the evidence is being adduced. Do you want us to give this particular document a separate number?

MR COONAN: They could go in D2 or they could be wholly separate. It is not so much a defence document. It is simply a collating exercise.

THE CHAIRMAN: We will put that in D2. Do you agree, Ms Smith?

MS SMITH: I am in your hands, sir.

THE CHAIRMAN: Thank you. We will put them in tab 17. (Document distributed)

Examined by MR COONAN, Continued

Q Dr Wakefield, we were coming to the end of the topic of transfer factor when we completed your evidence last evening. I would like you to take up volume 3 of the Panel bundle and turn first of all to page 941. So we can pick up the thread of this, this is now in July 1998. I draw attention to the first paragraph of this letter from Professor Walker Smith to Professor Zuckerman:

“Thanks for your advice. I shall not write to David Hull. I have now written to Dudley Dumonde who I have known for many years concerning the safety aspects of ‘transfer factor proposal’. I attach copies of these”.

Were you aware at around this time of correspondence relating to Professor Dumonde?

A I was not involved in this correspondence, but I may well have been aware of it. I do not remember it, but I may well have been aware of it.

Q It is the background to the correspondence that I need your help about. Let us look at the background to that comment by Professor Walker Smith on page 941. If you go to page 936, we see a handwritten letter from Professor Walker Smith to Professor Zuckerman. There is a note at the bottom of the letter from Professor Zuckerman that is discussed,

“Not to reply to David Hull directly, to seek Michael Pegg’s views to seek advice from Ivan Roilt and Dudley Dumonde re TF”.

That is a bit of a background. We come to the subject matter of that background by turning to page 943. This is Professor Walker Smith’s letter to Professor Dumonde, Professor of Immunology at St Thomas’ Hospital on 15 July 1998.

“Re Transfer Factor.

You doubtless will have heard about the controversial findings Wakefield et al have reported concerning the possible role of measles in children with autism”.

Pausing there, this is after the publication The Lancet paper is. Is that right?

A Correct.

“A study is proposed to give a group of such children who have evidence of measles antigen in tissue, positive meales serology and PCR posivity in circulating lymphocytes, dialysable lymphocyte extract transfer factor. There will be patients under my care and I will be responsible for safety aspects.

As I have known you so long and always valued your advice, I would much appreciate your confidential opinion of the safety of this extract as will be supplied to us by Dr Charles Kirkpatrick, Professor of Medicine & Immunology, University of Colorado, USA.
I have discussed this matter confidentiality with out Dean, Professor Arie Zuckerman, and we both would value very much your advice, which I could pass on in confidence to Dr Michael Pegg, Chairman of our Ethical Committee if you were willing for me to do that. Or else you could give me your own opinion in confidence”.

Can you help as to the underlying reason why an approach is being made to Dr Charles Kirkpatrick about safety?

A By this stage clearly, as the Panel heard yesterday, an extensive evaluation of the literature with respect to safety had been undertaken. Professor Zuckerman, who had some experience of the use of transfer factor, clearly wanted further reassurance and asked Professor Walker Smith to make contact with Dudley Dumonde who was Professor of Immunology at St Thomas’ at the time and also highly experienced in the field of transfer factor. I think it is an entirely reasonable thing to do, to assuage any anxieties he might have had about that. One particular aspect of this is that Dr Fudenberg’s transfer factor was made from goat’s colostrum. The source was to be goat’s colostrum. That is the first milk issued by the goat following birth of a baby goat. It is effectively, as Professor Lachmann has said, like drinking goat’s milk, but that was the source of it. In contrast, the transfer factor that was going to be provided by Professor Charles Kirkpatrick was bovine in source. It was from cows. The only specific safety issue that this raised over and above the prior evaluation of safety was the possibility of bovine spongiform encephalopathy that there may be the potential for transmission of prions in the cow based preparation which clearly was not a problem with the goat based preparation. There was an additional safety element that needed to be addressed albeit that of course at that stage no evidence of prions or bovine spongiform encephalopathy had ever emerged in herds of cattle in the United States.

Q Turn to page 960. We have now moved on to 23 September 1998, Professor Walker Smith to Dr Pegg copied to you we can see at the bottom of the page, the communication is in respect of the study 22 98 that we looked at yesterday. Do you see that?
A Correct.

Q It reads,

“Many thanks for your letter. I apologise for not replying before but there has been some time involved in determining details of European Safety Standards requirements. We have no doubt that the transfer factor produced is safe but Dr Andy Wakefield will be flying shortly to Denver, Colorado, to see the manufacturers to ensure that all the details of the European Safety Standards are met. It will thus be possible for us to have the information ready for the October Ethical Committee meeting but will be for the following. I hope this is satisfactory. Yours sincerely”.

First of all, was that a correct state of affairs that you were in fact about to fly to Denver?

A That is correct, yes.

Q Did you?
A Yes.

Q Can you just help the Panel about the relevance flagged up here of European Safety Standard requirements.
A Again, I think this was a matter that arose in relation to the possible contamination of bovine products with prions from the bovine spongiform encephalopathy.

Q I appreciate you have dealt with it yesterday but it may be convenient to deal with it again, bearing in mind the focus of the charges, when you were addressing the question of Child 10 being provided with transfer factor towards the middle and towards the end of 1997, was that in relation to the transfer factor produced from goat’s colostrum?
A Yes, it was.

Q Were you in any doubt that that was safe based upon the advice you had received and the literature that you had gone to?
A No, I had no concerns.

Q Can you turn back to page 944, please? This is a letter from the Medicines Control Agency to Professor Walker Smith and I take you to the date of this, Dr Wakefield, 6 July 1998. Were you aware of this correspondence?
A Yes I was.

Q The Clinical Trials Unit writer of the Medicines Control Agency heads the letter in relation to transfer factor. In relation to a piece of UK legislation at the top.

“I am writing in connection with your notification dated 01 July 1998 [under that piece of legislation] which relates to a proposed trial Dialysable Lymphocyte Extract Transfer Factor supplied by Division of Clinical Immunology Department, University of Colorado”.

Again, was that the basis of the study that it should come from Colorado?
A Correct.

Q The notification document, in case one needs it for completion, is on page 945 through to 947. Is that right?
A Correct.

Q That completes the section for my purposes on transfer factor.
I am turning to a wholly different topic and, for those who may wish to follow the route map, it is section 10. I am now concerned, Dr Wakefield, with The Lancet and the various aspects of The Lancet and associated correspondence looked at from different angles as we go through this. For present purposes, you will not need volume 3 yet, so if that is encumbering you, you can put it to one side. You might care to have volume 2 and turn up the paper itself.
Please turn to page 783. We can, if necessary, see from the chronology of referrals, admissions and investigations document that Child 10 had been investigated in February of 1997. By that stage, had all the children who were to become what has been called The Lancet 12 been investigated?
A Yes, they had.

Q Including one chid that we have not been looking at, which is Child 11?
A Correct.

Q Was a decision taken to write what became this paper?
A Yes, it was.

Q When was that decision taken?
A It will have been taken in or around January or February of that year. What had happened was that we had reached a natural hiatus, if you like. The pilot study as referred to in my letter to Dr Pegg had been completed. We had gained information from the analysis of the initial 12 children that had caused us to modify our approach, and in particular the clinicians had decided to remove the neurological investigations since they were not yielding any valuable clinical information that modified the child’s management, and in addition I was seeking, as you may remember, to include a further experimental aspect to 172/96 – that is the measurement of intestinal impermeability. So at this stage a natural hiatus had been achieved, if you like.

Q Was there one person who took a decision to write up this material? Was it more than one? How did the dynamics work?
A All of these decisions are ultimately a consensus. Someone initiates the process and I may well have suggested it and initiated the drafting of that, what was to become, The Lancet paper.

Q Let us first of all look at the nature of the paper as it came to be published, and we will go back and look at the mechanics that went into it. At the top left-hand corner and also the top right-hand corner there is the phrase “Early Report”. From your standpoint, what was the fundamental nature of this document?
A This is a case series in the classic mode of case series descriptions in the medical literature.

Q As a description, can that be distinguished from other descriptions of other papers and other types of study?
A Yes, indeed. A case series seeks to report the experience of a patient or a series of patients with a similar presentation or diagnosis – not identical, not the same necessarily but a similar presentation, similar features, a similar diagnosis. It is often the case in clinical medicine that a physician observes a pattern emerging, commonalities, factors that overlap in the presentation or findings in a group of patients that merit publication in a case series.

Q There is a reference to the phrase “Early Report” which you can find if you go back in the same bundle to page 615. We look at this in a different context but it may be timely to look at this section. In the left-hand column on page 615, it is from the 4 October 1997 edition of The Lancet. I just draw attention to the section which reads “Early Reports”.

“Early reports may simply be preliminary – the first results from a study whereas subsequent analysis is planned, for example, or an incidental interesting observation from a study set up with another purpose – or they may be early in the sense of being well short of changing clinical practice. These papers will tend to be shorter than Articles.”

Again, is that helpful in assisting with an understanding of the concept of an early report?
A Yes, indeed. This is a designation provided by The Lancet. We did not submit it with that suggestion but nonetheless that is how they interpreted it as being best represented.

Q So in terms of a case series, were you – I say “you” for the moment and I am using that in a collective sense – writing up the preliminary results of an overarching research project?
A No. What we were doing and in the classic mode of case reports is taking the parental histories, taking the clinical findings, taking the results of the tests that had been performed and in this case with the additional element of a detailed analysis of the research biopsies in a standardised way correlating those findings in the form of a case series.

Q Did the work which was written up in this paper include work which was in fact done in pursuance of the Legal Aid Board pilot study?
A No.

Q Again, in case it is necessary, can you just spell out why that is the case?
A The Panel will remember that the Legal Aid Board pilot study was a viral detection study based upon the analysis of biopsies taken from children during the course of their routine colonoscopy and was to include five children with autism and bowel symptoms and five children with Crohn’s disease. That matter finds no mention whatsoever in The Lancet paper.

Q The Panel will be only too well aware of the subsequent correspondence of observations and critiques and so on and so forth in relation to this paper. I am going to ask you, Dr Wakefield, in fairness to you and your co-authors, just to summarise. Do not repeat what is in the paper because we can read it. Can you summarise, please, what claims the paper made and what claims, the paper did not make? Can you do that for us, please?
A The paper laid down a provisional claim for the identification of what appeared to be a novel inflammatory bowel disease in children presenting with a regressive, pervasive developmental disorder. The finding was one of a combination of swelling of the lymph glands in the intestine – lymphoid nodular hyperplasia – and inflammation in the form essentially of colitis – inflammation of the colon. In addition, there were disturbances in what appeared to be vitamin B12 metabolism and there was a temporal association reported by parents or practitioners in some children with an environmental exposure. In some that was MMR vaccine; in one child it was measles infection; and others noted no exposure associated with the onset of symptoms at all. In essence, that is what was reported.

Q So that again the Panel can re-read in the light of what you are saying. Was the nature of those exposures spelt out explicitly in the body of the paper?
A Yes, it was.

Q Can we find that in tabular form in the paper?
A Yes.

Q What did the paper not claim?
A The paper did not claim that the bowel disease was definitely novel or confined to this group of children. It did not claim any causal association between the exposure cited by the parents or referring physicians and the onset or presence of bowel inflammation or developmental regression.

Q That, Dr Wakefield, represents the overall structure, does it, of the paper, which the Panel can re-read if necessary against the background of what you have just said?
A Yes.

Q In addition to The Lancet paper, was another paper drafted?
A Yes, it was. Submitted with this paper – I think we have a date going back to May 1997 – was a second paper, in this case a scientific paper that has been referred to previously, particularly by Dr Candy, and this was a preliminary analysis of the biopsies from these children undertaken in my laboratory for the purpose of detection of viruses, including measles, by the technique of immunohistochemistry.

Q Was it intended from your standpoint that the two papers should be, first of all, submitted together and, if you were successful, published together?
A Yes to both questions.

Q What was the underlying reason, from your standpoint, for having first of all two separate documents and secondly that a reader would be able to read one in the light of the other and vice versa?
A The first paper, the one paper that was published, as in a case series, is not in essence a research study. It is a report, a clinical report. However, in light of the parental association in some cases with an environmental exposure, it raised a question and would do so in the minds of the readers that here a possible association between an exposure to a vaccine for example and onset of symptoms is being posited, at least in the minds of the parents. It seemed reasonable therefore to try and pose at least a provisional answer to that question by submitting at the same time a paper addressing this specific issue. I should emphasise that the presence of measles virus in the intestine, if that turned out to be the case, does not make it the cause, but it is the first rung on the ladder, if you like, of seeking to answer the question of whether there is or not a causal association between this exposure and the onset of problems.

Q Was the science paper the same as the LAB pilot?
A No, it was not.

Q You have told us that the science paper and what was as it came to be published The Lancet paper were submitted, and you referred to May 1997. We looked at that yesterday. Just remind us in this context again: when did the LAB pilot begin?
A The Panel will remember that the funding for the LAB pilot study did not become available to be spent and therefore by definition the LAB pilot study could not have started until at least September of 1997.

Q We do not have a copy of the science paper as submitted to The Lancet but can I ask you now in Volume 2 to go to page 638? First of all, can you identify this document for us?
A It is a proposal for a collaborative clinico pathological study between various departments at the Royal Free, the Department of Biochemistry in Birmingham, the Autism Research Unit at the University of Sunderland, the Department of Medicine and Biochemistry at King’s College Medical School in London, and the Department of Paediatrics in Tokyo Children’s Hospital, in Japan.

Q If I take you, in fact, first to page 639, just over halfway down this page there is a reference to, and I will take you to the actual heading please, “Clinical study, (Lancet 1998); in press)”. Was that a reference to The Lancet paper that became published?
A Yes, it is.

Q If you go to page 640, you see a reference to “Laboratory studies (Lancet 1998; submitted for publication”. So far as the heading is concerned, what is that a reference to?
A This is a reference to laboratory based analysis, either clinical or experimental, in relation to virological aspects of this condition.

Q Was there any connection between what follows in that text, page 640, and the science paper?
A Yes, almost certainly. I think this is a summary, at least in part, of some of the aspects of that science paper.

Q When the science paper itself, if I can go back to that, was submitted, was that paper rejected by The Lancet?
A Yes, it was. I should just add the PCR, the polymerase chain reaction, element to this, was not part of that science paper. I am sure that had not been done by this time it was submitted, but this science paper was indeed rejected, yes.

Q I will come back to the processes in a few moments. I want to ask you, please, now if you go back to the paper itself at page 783, in volume 2, we will see the title and then underneath it the authors’ or contributors’ names.
A Correct.

Q I want to ask you, please, about the significance or otherwise of the presence of these names and the order in which they appear. Why are you named first?
A I was the co ordinating investigator.

Q And why is Professor Walker Smith named last?
A It is common policy for the senior author, in this case the senior clinical author, to take the last place in authorship, and that is the practice here.

Q Is there any significance from your standpoint that Dr Murch is after you, before Anthony, who is before Linnell, who is before Casson, et cetera, et cetera?
A To the extent that he is senior to the others and that he was involved intellectually and practically in the evaluation of the children.

Q Putting it another way, is there any significance that, for example, Dr Linnell is first in time compared with, say, Dr Harvey, or Dr Davies?
A Not really. Beyond the first, second and last author, it really then is just a question of a perspective of relative contribution, if you like, relative volume of contribution.

Q Now, in relation to your role, in terms of the drafting of a document like this, how do you perceive your duty to be?
A My duty is to produce a preliminary draft which brings together the clinical information, any experimental or research information, and try and assemble them into a coherent paper, which is then circulated to all collaborating authors for their input, their criticisms, their comments, their suggested changes.

Q And what about the accuracy or otherwise of the data you are looking at?
A One relies upon the records one has available, and upon the input from one’s expert colleagues specifically in relation to their areas of expertise.

Q I asked you this in relation to each of the children as we went through them. When you started off putting together a first draft of this - and deal with this, please, compendiously - what materials were you able to go to to uplift the information?
A I had for each child the full contemporaneous clinical record: I had, wherever it could be obtained, the data from the child developmental records which were ascertained in order to compare what had been contemporaneously noted in the child’s development, with the history given by the parent at the Royal Free, and in addition the standardised pro forma histopathology document that had been designed and completed by Dr Dhillon.

Q You mentioned during the course of your evidence developmental records of the children.
A Correct.

Q Were those the red books that you referred to?
A That is correct, yes.

Q And we see a reference to that, do we not, at page 784, if you look under the heading of “Results”, and drop down to the fifth line?
A Correct.

Q And just help the Panel, please, insofar as it may be necessary, mechanically how did you go about obtaining the raw data in order to write a draft?
A I will have accessed the patient’s clinical record. Either the document will have been held in the Department of Paediatric Gastroenterology for a reason or I will have obtained it from the medical records department.

Q And did you, in fact, do a first draft based on that data?
A Yes.

Q And did you circulate that draft?
A Yes.

Q Who did you circulate the draft to?
A The initial draft will have gone to all authors on the document.

Q Did you get responses from those contributing authors?
A Certainly from the majority, yes.

Q We may have to look at a number of specifics in a minute, but what would be the general nature or flavour of responses back?
A There would have been

MR COONAN: Just pause, Dr Wakefield. It may be slightly offputting but the sound is not perfect.

THE CHAIRMAN: Yes. Ms Smith, are you having difficulty?

MS SMITH: I am, sir, but I think Dr Wakefield may be a little close to the microphone.

THE CHAIRMAN: Yes, that may be it. Please continue, Dr Wakefield.
A Sorry. Where was I?

MR COONAN: Dealing with the general flavour and nature of responses from the co ordinating authors.
A Responses may have come in two ways, one by virtue of annotations in the draft document that was circulated or, alternatively, during our Tuesday interdisciplinary meetings held in the Department of Gastroenterology there would have been discussion about changes to the paper at that stage.

Q And again, in broad terms please, did you get feedback certainly on the initial draft from Professor Walker Smith?
A Yes.

Q Did you get feedback from Dr Berelowitz?
A Yes.

Q Did you get feedback from Dr Thomson?
A Yes.

Q From Dr Murch?
A Yes.

Q From Dr Davies?
A Yes.

Q I want to turn, now, please, to the title of this paper. The title heading is “Ileal lymphoid nodular hyperplasia, non specific colitis” and it is this part I want your help with “pervasive developmental disorder in children”.
Was there an original title or titles for this paper?
A Yes. I believe that it was entitled “Regressive Behavioural Disorder”.

Q Was that in the first draft?
A I think so.

Q Now, please, in volume 2, can you go to page 505? It is a letter from Dr Berelowitz to Professor Walker Smith dated 5 August 1997, and we will come back to the first page but for present purposes let’s look at the last paragraph, please.

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

That area was copied to you in the bottom left hand corner. Do you remember absorbing that suggestion and advice from Dr Berelowitz?
A Yes, indeed. The title was then changed to “Developmental Disorder”.

Q And did you understand the basis for Dr Berelowitz making that suggestion?
A Yes, I did. It was clearly more than just aberrant behaviour in children: it was a functional abnormality of their development that was the principal problem.

Q And we can see an expression of that. If you go to page 758, the title, apart from the gastrointestinal aspects, now reads “Developmental Disorder in Children: A New Syndrome”, not quite the final title at that stage, but at page 758 was that an attempt to give effect to Dr Berelowitz’ suggestion?
A Correct.

Q The final title, if you go back to the paper itself at 783, dropped the interrogative at the end that we have just been looking at and instead of “Developmental Disorder” simpliciter is now described as “... pervasive developmental disorder in children”. Was that title a title agreed to, as far as you are able to say, by everybody?
A Yes, it was. During the stage by which The Lancet had accepted the paper and sent us a galley proof, that is a draft proof for correction of typographical errors, for example, this draft galley proof was circulated to the authors and Dr Berelowitz returned to me with the suggestion that the word “pervasive” should be included, since this is a term used by child psychiatrists, Pervasive Development Disorder, or PDD, under which the umbrella of autism, disintegrative disorder and Asperger’s syndrome sit.

Q Whatever the reasoning may have been, was the title following that then circulated to everybody?
A Everybody agreed on that amended title - the senior authors. By this stage it was not going to the junior doctors.

Q I understand but, using your definition of senior doctors, who is the Panel to understand would be included in that at this stage?
A I think this would include Dr Berelowitz, Dr Harvey, Professor Walker Smith, and Dr Murch.

Q Now, I promised that I would go back to the letter at page 504, and let’s do that now, please. Since it is a long time since the Panel saw this, I am going to read the earlier part of the letter. This is 5 August 1997.

“Dear John, it seems clear from the events in 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” I think that should be “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 carries the right sort of emphasis and that possible causal link is not ‘over stated’.”

Pausing there, in relation to a possible causal link being overstated, was that suggestion given effect to in the published document?
A Yes, it was.

Q In particular, again the Panel can read it, towards the end of the article at page 787.
A Correct.

Q He goes on,

“Secondly, my preference would to be 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 form 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 vaccination”.

First of all, did the paper pick up and repeat verbatim that suggestion?
A No, it did not.

Q Did you consider that suggestion?
A Yes.

Q Was a decision made not to include it?
A Yes, the paper had no role whatsoever in offering advice one way or another about vaccination. That was not its purpose. Its purpose was to report the parental history.

Q Whose decision was it not to pick up Dr Belelowitz’s suggestion and run with it and reproduce it in the paper?
A I cannot remember precisely, but I certainly would have agreed with that suggestion.

Q Which suggestion?
A That it should not be included.

Q What I want to clarify with you, can you help the Panel was it a unilateral decision by you or did it involve anybody else?
A To the extent that the letter was sent to Professor Walker Smith and others, then it must have been in accord with their own perception, yes.

Q That letter was written to Professor Walker Smith but copied to those four people, Dr Wakefield, Dr Murch, Professor Taylor, and Professor Pounder. Can we turn, again this is part of the mechanics of the process by which this paper came to be published, look for a minute or two at the role of The Lancet editors. As the corresponding author, did you have the channels of communication with The Lancet?
A Yes I did.

Q Was it just you who had those channels?
A It was not an exclusive arrangement, but it is the formal way in which these things are done that there is a corresponding author and that was me.

Q Was there a particular editor that you dealt with?
A Yes, there was.

Q Who was that?
A Dr John Bignall.

Q Did you have written correspondence with Dr Bignall Panel or telephone communication? How did it work?
A Written correspondence.

Q Did he make any suggestion about the drafts of the text?
A Yes. He will have sent it out or had been responsible for sending it out for the peer review. The reviewers will have come back with various comments and he will have articulated those comments in a letter to me suggesting that we needed to make changes to the paper in accordance with the reviewers’ recommendations.

Q As far as you recall it, were those amendment made in accordance with the suggestions coming from Dr Bignall.
A Yes, they were.

Q Can you remember now what the volume or numbers of suggestions Dr Bignall was making?
A I do not remember the precise comments. It may have required, as is often the case with The Lancet, a shortening of the text. The Lancet is fairly brutal in its editing process and restricts authors to a certain number of words. There would have been in the first paper in its preliminary submission a reference to the second paper because they were intended to be linked, something to the effect of, “In an accompanying manuscript we describe” and so on and so forth. That clearly, following rejection of the second paper, the science paper, would no longer have been relevant and that will have been removed.

Q Who, as you saw it, was involved in the rejection process of the science paper?
A One does not get to find out the names of the reviewers. This is done in an anonymous way, but from the statements made, I believe it must have gone to some expert virologists.

Q What about the editorial stage, was Dr Bignall as you could see it, involved in that process or not?
A I am sure he was. I suspect that there is a joint meeting of editors where the reviewers’ comments are assessed and a decision made.

Q Were you told at any rate by letter that the science paper was going to be rejected?
A Correct.

Q Whose letter was it who told you it was being rejected?
A It will have been from Dr Bignall.

Q Can I please look with you at a number of aspects of the text. Can you turn to page 758, just to identify this, you told us that there were earlier drafts. We can see from the top of the page that this is not, as you have identified already, the final drive draft from the title itself.
A Correct. This paper will have gone through probably 30 to 50 such drafts.

Q Taking this as a draft at some stage, I want to turn, please, first of all to page 770. In the paragraph in the middle of the page beginning “Lucarellis” do you see that?
A I do.

Q On the third line there is a sentence beginning, “Similarly”.
A “Correct.

Q Down to the end of that paragraph we can see what it says. If you then go to The Lancet paper itself, has that section been deleted from the published document?
A Can you just remind me of the page of The Lancet paper?

Q Page 783.
A That aspect of that paragraph has been removed.

Q Do you remember now the circumstances and the reasons why that was deleted?
A As I have mentioned, the paper was overly long and that was considered one element that might be redundant.

Q Page 771 at the bottom of the page there is a sentence beginning on the penultimate line,

“It is important to note that the present study does not constitute proof of an association between MMR and the syndrome described: detailed virological studies are underway that may help to resolve this issue”.

If you turn to The Lancet paper at page 787 in the top left hand corner, is the text different?
A Yes it is.

Q Can you read out the text in the published paper?
“We did not prove an association between measles, mumps and rubella vaccine and the syndrome described. Virological studies are underway that may help to resolve this issue”.

Q Can you remember now the circumstances in which that amendment came to be made?
A Again, this will be a word cutting exercise.

Q By whom?
A Probably by The Lancet themselves.

Q On page 772 five lines down,

“If there is a causal link with the MMR then a rising incidence might be anticipated following its introduction in 1988. Despite an impression of arise in autistic spectrum disorders, published data are inadequate to determine whether there is either a raising incidence or a link with MMR. The diagnosis of autism is usually made on symptoms starting in the first year of life, when children receive MMR. Despite the striking temporal association with MMR in many of these children, this factor must be taken into consideration when examining the apparent association described”.

Did that undergo a change as represented in the final draft?
A Yes it did. This was removed.

Q What was the basis for removing it?
A It had been put in as part of the request of Dr Berelowitz, but it was in fact factually incorrect. The diagnosis of autism is usually made on symptoms starting in the first year of life. That is classical autism according to Dr Belelowitz’s teaching, but they do not receive their MMR vaccine during the first year of life and, therefore, since it was factually incorrect it was removed.

Q Just remind us, we have heard evidence about it, when do children habitually receive their MMR?
A At that time I think it was 15 to 18 months of age.

Q Whose decision was it, at least initially, that that part of the text should be removed?
A In view of the fact that it was factually incorrect it may well have been my decision to remove it.

Q Again, it having been removed, was the surviving text then the subject of recirculation to others?
A Yes.

Q The final matter I want to ask you about in relation to the drafting process is a matter on page 764. Dr Wakefield, there is one caveat; I am going to come back to this in a different context. I just want to establish what happened and then we will come back and ask for your background evidence on it. You will see on page 764 under the heading of “Ethical approval” it says,

“This clinical investigation has been approved by the Ethical Practices Committee of the Royal Free Hospital NHS Trust”.

If you now look at the paper itself on page 784, the heading is now as we can see “Ethical Approval and Consent”.
A Correct.

Q The text reads,

“Investigations were approved by the Ethical Practices Committee of the Royal Free Hospital NHS Trust, and parents gave informed consent”.

Can you help about the mechanics by which that change occurred?
A I can. Clearly in the draft that this clinical investigation has been approved is incorrect. Clinical investigations do not require approval. What does require approval are research aspects that are an adjunct, as in this case, to those clinical investigations, those do require approval.

Q Can you remember now who it was who made the amendment to give effect to the matter as you have explained it?
A I do not know who drafted it or who picked it up, but it would have been picked up and it will have been my secretary who entered that amendment into the next draft of the paper.

Q Leaving aside the precise mechanics, the secretarial level, did you have any input into effecting that change to give effect to the reasoning that you just explained to the Panel?
A Yes, I would have done.

Q Again, was a subsequent draft, representing that which is set out on page 784, circulated before publication?
A Correct.

Q As far as you know, did you have any objection to that terminology being used?
A Not at all. It is ultimately a consensus statement as is the entire document to which the senior authors in particular must agree, but it is correct for those investigations that required ethical approval there was such ethical approval.

MR COONAN: Sir, I am going on to section 11. Sir, I am in your hands as to when you want to take a mid-morning break.

THE CHAIRMAN: If you are going to move to the new subject, this may be the right time to take it. We will now adjourn and resume at 11.15. Dr Wakefield, you are still under oath.

(The Panel adjourned for a short time)

MR COONAN: The next section of Dr Wakefield’s evidence concerns the contents of The Lancet paper. If you turn to the paper itself, Dr Wakefield, at 783, looking at the title again, and it is a different aspect of the title I am going to ask you about, the title of the EC Application 172/96 is of course different than this title. To remind ourselves, it might just be helpful to turn up in volume 1 at page 201 to look at it again. Right at the top of 201 the question is this. Is there any significance to be attached to the difference in description for the two titles?
A As I have mentioned to the Panel before, one of the enduring errors in the prosecution of this case has been the conflation of The Lancet report with 172/96. These children were not admitted and investigated under 172/96.

Q You can put volume 1 back, please. Can I now take you back to the paper? I just want to look at a couple of references in relation to the roles of various people. Can you turn to page 784 first of all of volume 2? Under the heading of “Histology” on the left-hand column you see the reference to various people.
A Yes.

Q Is the description there of the roles of those people accurate?
A Yes, it is.

Q If you look at page 787, bottom left-hand corner, under the heading of “Contributors”, is that description accurate?
A Yes, it is.

Q Go back now please to the first page of the paper at 783, and I am going to pick out a number of specific references. I am going to start by looking at page 783 and the left-hand column under the “Summary” heading and the subheading “Background” where you have written:

“We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder.”

Then, just to flag it up, under the “Methods” you say: “12 children” and then you set out the mean age and I will skip that,

“12 children …. were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain.”

The summary goes on. Dr Wakefield, I want you, in relation to that description of a consecutive series, to deal with that in the light of your evidence that you have given in respect of each of 11 of these 12 children as to the manner and mechanics of their referral. You appreciate some criticism is made of the use of that term. Do you accept that criticism?
A No, I do not.

Q Can you tell the Panel what you intended to convey by the use of that phrase “consecutive series”?
A It is a precise and entirely accurate description of this group of children. They were the first 12 children with this specific presentation who were referred and seen at the Royal Free and to have presented this without that information might imply to anyone that we saw many more children but selected from those children the ones that we felt fit the pattern. Therefore, it is essential to use the word “consecutive” to emphasise that that form of selection bias did not take place.

Q A similar phrase is used on the right-hand column on the same page under the heading of “Patients and methods”.

“12 children, consecutively referred to the department of paediatric gastroenterology….” and then it goes on “with a history of a pervasive developmental disorder”, et cetera, et cetera.

I will deal with that part in a minute. “Consecutive series” and “consecutively referred”: is there any distinction between those two descriptions in principle?
A No, they can be taken to mean the same thing.

Q And the reference to, in the left-hand column, “a history of normal development” and then in the right-hand column under “Patient and methods”,

“a history of a pervasive developmental disorder with loss of acquired skills and intestinal symptoms (Diarrhoea, abdominal pain, bloating and food intolerance), were investigated”.

Then under the next heading, “Clinical Investigations”,

“We took histories, including details of immunisations and exposure to infectious diseases, and assessed the children. In 11 cases the history was obtained by the senior clinician (JW-S).”

The reference to “a history of”: what did you intend to convey by the use of that expression in this paper?
A That specifically refers to the history of the child obtained from a distillation of the entire contemporaneous clinical record.

Q One of the criticisms made of you was the fact that in some cases – and we will look again at the numbers as it is fact – there is no reference to GI symptoms in one or other of the referral letters. Correct?
A Correct.

Q As I understand it, it is therefore said that what is written here is therefore incorrect, inaccurate and misleading. What do you say about that?
A I dismiss that completely.

Q Why?
A As I have said, the histories, including the gastrointestinal history, were derived from a distillation of the entire contemporaneous clinical record, and in particular that taken by Professor Walker-Smith and his team at the Royal Free, and the fact that in some referral letters there was no mention of gastrointestinal history is something that is irrelevant to the paper and certainly for which Professor Walker Smith and his team should not be held accountable.

Q As a separate matter, and you will tell the Panel whether this is relevant, before these children were referred, were you yourself aware of the existence of GI symptoms?
A Yes, I was in every case, or in the great majority of cases where I had had contact with the parents, with the mother or father spontaneously making contact with me that gastrointestinal history had been evident.

Q On page 783, and I have referred to it already in laying the ground to the question but I take you back to it, under the heading of “Clinical Investigations” on the right-hand side, you say: “We took histories…” Was that true?
A Correct. This is a question of style and applies across the collaborative team.

Q I want to go to page 785 and to the Discussion section on the right-hand column.

“We describe a pattern of colitis and ileal-lymphoid-nodular hyperplasia in children with developmental disorders. Intestinal and behavioural pathologies may have occurred together by chance, reflecting a selection bias in a self referred group; however, the uniformity of the intestinal pathological changes and the fact that previous studies have found intestinal dysfunction in children with autistic-spectrum disorders suggests that the connection is real and reflects a unique disease process.”

I want you please to concentrate on the first part of that paragraph:

“Intestinal and behavioural pathologies may have occurred together by chance, reflecting a selection bias in a self-referred group…”

Can you tell us, please, what you are intending to convey by the use of that phraseology?
A Yes. One of the things that a medical paper such as this must do is to proactively highlight potential shortcomings or any interpretation that one might place upon the observations, and here we do exactly that. By referral, we refer to the possibility that patients presenting with gastrointestinal problems and with concomitant developmental problems may have occurred by chance because it is the parents who have initiated the referral. The “self referred group” refers to the fact that it is the parents who have initiated the referral. Let me try and explain very simply. It may be that bowel symptoms occur in many children with autism but at no greater rate than the rest of the population of children, but word may have got around that at the Royal Free we are looking at children with gastrointestinal symptoms and developmental disorders, and so through parental networks there is an excess of those children being referred to us, creating the impression that there is a real association between bowel problems and autism when in fact it may be an artefact of the self-referral process.

Q Were you flagging up that underlying possibility?
A Yes, we were.

Q In terms of the parents seeking or initiating a referral, are you comfortable with the description that it was a self-referred group?
A Absolutely; it describes them precisely.

Q Let us look at a number of other factors which are levelled against you as I understand them, that there should have been explicitly said here that Dawbarns were involved in the referrals. Now, as far as you were aware, were Dawbarns involved, and I am using that word in a very broad sense, involved in the referrals?
A Absolutely not.

Q One other matter: were you aware when you were considering contacts made with you by parents that a parent may have wished for an examination of a link which they perceived between MMR and the bowel/brain connection? Were you aware of that, that that may have been in the minds of some of these parents?
A Yes, absolutely. In seeking to get to the bottom of their child’s problems and the symptoms from which they were suffering, some of them had made an association with the vaccine exposure and were keen to determine whether that was, in fact, valid or not.

Q Again, should that have been explicitly stated in this paper?
A It was explicitly stated in the reiteration of the histories of the parents.

Q Is the reference to “self referred” inconsistent with your understanding of the parental perception of such a link?
A Not at all. It is entirely consistent with it.

Q What about the possibility that a parent may be motivated, at least at the outset, by litigation considerations? First of all, to what extent were you aware of any parent being motivated by such considerations?
A At the time that they contacted me and at the time of the referral of their child to Professor Walker Smith, the issue of litigation was not on the agenda for these parents. The only child for whom I was aware of litigation who did not appear in this paper was discussed yesterday, Child JS, and I have to say that the fact that a parent later may have considered or been interested in litigation would certainly not have biased me in any way, or Professor Walker Smith, against investigating them for clinical symptoms.

Q Insofar as, to your knowledge, a parent may have been motivated to examine by investigation the link between MMR and the bowel and the brain, was that in any way inconsistent with either the descriptions used on 783 in the left hand column, viz “consecutive series”, or in the right hand column, viz “consecutively referred”?
A Not at all. The fact or otherwise of an exposure or putative exposure identifying the parents played absolutely no role. As you can see from the histories in the paper and as referred to by Mr Horton in his evidence in selection of cases for investigation, this was purely based upon their clinical symptoms.

Q Then could you deal with this point: insofar as a parent may have initiated a referral by going to his or her GP, you have told the Panel that on some considerable number of these cases there was a parental contact with you, and then a contact been you and the GP. What do you say to the criticism, as I understand it, that there was contact between the Royal Free Hospital, in other words yourself in the main and the referring GP? Was that something that should have been explicitly spelt out in this paper?
A Something like that has no place in this paper at all. What I was acting as was a signpost for this child to get an appropriate referral. That contributes absolutely nothing to this paper, or its interpretation over and above the fact that these children were self referred.

Q And was the fact that you had that contact with the GP, as you have described, in any way inconsistent with the description, and I am looking at 785, right hand side, where you say that this was a self referred group?
A Not at all, no.

Q Is it in any way inconsistent with the description on 783 in the left hand column, “consecutive series”, and in the right hand column, “consecutively referred”?
A No.

Q When you used these descriptions, were they honestly made?
A Yes.

Q And were they agreed to by your co authors?
A Yes. the paper is a consensus document.

Q Did any one of those co authors say that that is an inaccurate or misleading or less than full description of what the position was?
A No.

Q Now, you have touched on the next point already in a different context earlier this morning but I want you now to deal with it in this context, and we go back, please, to 784. Under the heading in the left hand column, “Ethical approval and consent”, in the published version it reads:

“Investigations were approved by the Ethical Practices Committee of the Royal Free Hospital NHS Trust, and parents gave informed consent”.

So far as the first part of that statement is concerned, was that true?
A Yes.

Q And what were you intending to convey when you used that expression?
A That the investigations for which ethical approval was necessary, that is the adjunct scientific investigation, then it had been obtained.

Q And what approval was it?
A This was the approval for the analysis of biopsies taken pursuant to the routine colonoscopy under 162 95.

Q Following the comma, you say “and parents gave informed consent”. What were you intending to convey by the use of that expression?
A That the Panel have been taken to the informed consents in the records of each and every child, which refer to this particular statement.

Q Were both the two elements of that small paragraph accurate?
A Yes.

Q And were they true?
A Yes.

Q And were they agreed to by your co authors?
A Yes.

Q That is all I ask you about that section, Dr Wakefield. I am going to move on to the next section, where we are concerned with the matters of disclosure in The Lancet paper. Just to help the Panel and also yourself, in order to address the material I am going to be dealing with three separate matters. First, the matter of funding in relation to the LAB pilot: secondly, your involvement in the MMR litigation generally, in other words, the agreement to act as an expert, and, thirdly, the 1997 patent that we looked at yesterday. These are the three matters I am going to seek your assistance on.

I am going to deal with funding first. As matters stood in 1997, did you understand there to be, certainly as regards The Lancet, an obligation to declare funding in certain circumstances?
A Yes.

Q Can you specify what those circumstances were, as you understood them?
A Where the funding had been provided for the purpose of that specific project and was spent in the conduct of that project.

Q I will just pause until the Panel have made a note of that. (Pause.)
And so we are clear about this, is that a belief and understanding you had throughout 1997?
A Correct.

Q And is it a belief that you had leading up to the time The Lancet was published?
A Correct.

Q I want, now, to turn to the basis of that belief. Had you contributed to The Lancet before this paper?
A Yes.

Q And had you seen any guidance in previous Lancet publications touching on the question of declaration obligations?
A Yes, I had.

Q In The Lancet itself, and we can pick this up in volume 2 at page 615, I am going to remind you and the Panel of the date of this document, which we were told by Mr Horton was, in fact, 4 October 1997, and I am going to proceed on the basis that there were earlier editions of this document in exactly the same terms. We have not been told otherwise, so that is the position. Alright?
A Yes.

Q Had you read this document at page 615 going over to 616?
A I will have read it at some stage, probably in an earlier form when submitting previously to The Lancet, yes.

Q And it is in two pages, 615 and 616. Before asking you any questions about it, there is an earlier editorial at page 426 of volume 2. Is that a document that you recall having read before you submitted this Lancet paper?
A Is this the commentary on 426?

Q That is correct.
A I do not remember having read this specific commentary, no.

Q In terms of guidance to you as a potential author, or certainly an actual submitter of papers, what guidance would you rely on?
A In the context of the Lancet I would have relied on an earlier version of the Lancet, when I was submitting, for example, in 1995, and in addition from departmental members, in particular my line manager, Professor Roy Pounder.

Q And what about the material perhaps in an earlier version at 615 and 616?
A Yes.

Q Which is headed, is it not, at the top left hand corner on 615 “Writing for The Lancet”.
A Correct.

Q On page 616, there is a section in the left hand column which I am going to ask you to look at closely headed “Conflict of interest and funding”.

“The conflict of interest test is a simple one. Is there anything - eg a shareholding in or receipt of a grant or consultancy fees from a pharmaceutical company or a contract from a medical devices manufacturer - that would embarrass you if it were to emerge after publication and you had not declared it? The Editor needs to be informed and will discuss with you whether or not disclosure in the journal is necessary. All sources of funding must be disclosed, as an acknowledgement in the text”.

Did that passage, on the assumption it was reproduced in earlier versions of The Lancet, have any impact upon you?
A Absolutely. That was the disclosure requirement of The Lancet as I understood it at that time.

Q Did it inform you about the need or obligation to declare funding?
A Yes, it did.

Q In the way you described to the Panel a little earlier this morning?
A Precisely.

Q If you now go to the top of 615, I think I am going to skip the first paragraph and read the second one:

“The Lancet is a signatory journal to the Uniform Requirements for Manuscripts Submitted to Biomedical Journals, a document issued by the International Committee of Medical Journal Editors. The 1997 version (fifth revision) of that will” will “be posted on our website and it sets out the name.

Writing for The Lancet enlarges upon or emphasises what is in that document and in other pronouncements from that editorial group. Not all the answers you seek will be found on these pages and the journal’s editorial staff in London and New York will be pleased to help.

Whatever you have written, remember it is The Lancet that you are submitting to and that it is a general reader whom you are trying to reach. One way to find out if you have succeeded is to show your draft to colleagues in other specialties. If they do not understand neither, very probably, will The Lancet’s staff”,

and so on. Did you read that masthead?
A I have no memory of reading it.

Q Did you ever go to the website?
A No, I did not.

Q Do you know one way or the other what was actually on the website as of October 1997?
A No, I do not. My apologies, I do now because it has been disclosed during these proceedings.

Q At any rate, what material was relevant to your view of disclosure obligation at that time apart from the passage on 616 in the left hand column?
A As the Panel will now be aware, we have documentary evidence that the paper was submitted some time in May or before of 1997. This masthead, or its reference to the article on the website, clearly was not available until much later that year. Moreover, it refers to what is written in the writing for The Lancet this particular document enlarges upon or emphasises what is in that website document. There is absolutely no need as far as any author is concerned at that stage to go beyond this document, the published document in The Lancet, to ascertain the requirements of The Lancet for disclosure. They are, as Mr Coonan has read out, the issue about anything that would cause you embarrassment if it were to be disclosed at a later date and that was my modus operandi.

Q Let us look at what in fact happened, still dealing with funding. Was any funding sought, apart from two matters in a footnote which we will come into a minute, declared in the body of The Lancet paper?
A No.

Q What potential funding sources were available at that time?
A There was funding for Dr John Linnell from the children’s charity to conduct the analysis of B12, in particular for this paper, the methylmalonic acid, the spot test on the urine. In addition, there was funding available from the special trustees for the salary of Ros Sim who conducted in large part the accompanying scientific paper.

Q Can we go now to page 787 to the bottom hand corner. Under the heading of “Acknowledgements”, this study was supported by the special trustees of the Royal Hampstead NHS Trust and the children’s medical charity. Again, so there is absolutely clarity about this, can you please identify, now the Panel are looking at the reference, what those references are to?
A The special trustees, as you will remember, agreed to fund the salary of Ros Sim. She was the principal technician conducting the accompanying scientific paper.

Q And the children’s medical charity?
A That was the funding for Dr John Linnell to conduct the vitamin B12 analysis.

Q By the time The Lancet paper was published in February 1998, you had received first of all authority via Richard Barr for the expenditure of Legal Aid Board money in August 1996 and the legal aid money, and you gave the Panel your evidence, was available from September 1997. Was any Legal Aid Board money expended in any work which is enshrined by this paper?
A None whatsoever.

Q Does it make any difference to your answer that as you have told the Panel that the Legal Aid Board five plus five , if I can use that expression, had been selected by this time by Richard Barr?
A Again, no it does not.

Q Does it make any difference to your answer that the Legal Aid Board pilot had, in accordance with the evidence you have given, by the time of publication started?
A No.

Q Had any Legal Aid Board money been expended in the science paper?
A No.

Q Therefore ,can you help the Panel on this: against the background of The Lancet’s guidance on page 616, what was the reason at that time for not declaring Legal Aid Board funding?
A The Lancet requirement as it reads puts the emphasis upon the author, what might embarrass you if it were to be disclosed at a later date. That is clearly in the active mood and it is an easy issue to resolve. You sit down and you can think, “Well, what might embarrass me if it were to be disclosed at a later date.” If there had been funding for that project that had gone directly to that project and had not been disclosed, that would certainly be embarrassing ,and it was entirely appropriate to disclose that. However, was I embarrassed that I was conducting a pilot study on behalf of these children funded by the Legal Aid Board? Absolutely not. Therefore, I was able to reconcile that position in my own mind in the writing of this paper.

Q If Legal Aid Board money had been expended on aspects of the paper as it was written and published, would you have declared it?
A Absolutely.

Q Did you write a paper subsequently in relation to the Legal Aid Board work?
A Yes, we did.

Q Was that paper submitted for publication?
A Yes, it was.

Q Has it far not been accepted for publication?
A That is correct. It has been submitted on two or three occasions, but has not been accepted.

Q In the submitted papers relating to the Legal Aid Board work, was any acknowledgement made of Legal Aid Board funding?
A Yes, it was. Explicit acknowledgement of that Legal Aid Board funding was made.

Q When you drafted The Lancet paper as was published and submitted it and when you made no reference to Legal Aid Board funding, but made a reference specifically to the other two pieces of funding, at the bottom of page 787, were you conducting yourself honestly?
A Yes, I was.

Q I want to turn to the second aspect of The Lancet. That is the question of conflict of interest in ways out with the question of direct funding. In relation to these broader issues, what material or guidance was available to you when addressing that sort of question during 1997?
A Again, exactly the same documents as were available to me in the issue of funding.

Q Was there anything additional apart from pages 615 and 616?
A Or an earlier version thereof. That is the document upon which I relied.

Q Therefore, as you appreciate, the criticism is made that you should have declared in The Lancet paper that you had agreed to act as an expert in the MMR litigation, or at least you should have declared that you were involved in the MMR litigation. For my purposes, either will do. What do you say about that?
A Again, it is a question of interpretation, but the disclosure requirements of The Lancet are discrete and self contained. It says a simple one, a simple test. I was able to ask myself the question: do I feel that my agreement to act as an expert, if disclosed at a later date, would embarrass me? The answer is no. In fact, I am quite proud in an understated way that I had taken this position on behalf of these children. It was disclosed at a later date and I was not embarrassed. I did not feel it had any material impact whatsoever upon The Lancet. It was my colleagues who exclusively involved in taking the histories and the interpretation of the findings in these children. Those are the data upon which the paper was based, so, no, I did not feel there was a disclosure obligation of the fact that I had agreed to act as an expert on behalf of these children.

Q Dr Wakefield, were you dishonest in the way you approached matters in this regard?
A Not at all. The knowledge of my participation in the Legal Aid Board pilot study was in the national media. I think as early as November 1996. There was no secret and no deliberate attempt to conceal it at any stage.

Q I am going to turn to the end element which is the patent. It may be helpful ,just in case we need to look at it, to turn to the patent itself to remind ourselves of the nature of it. You will find that in volume 2 at page 479. It begins at page 478 and the text is at page 480 to 482 specifically.
A Mr Coonan, may I come back to the last point you just made because I may have said something in error and I am not quite sure what I said. Just in relationship to disclosure of the fact that I had agreed to act as an expert, not only was it in the national media, but of course it had been disclosed by the time of the publication to the Dean of the medical school, Professor Roy Pounder, Mr Blatch and to my colleagues. Quite rightly, in accordance with my own opinion, none of those people felt that it was a disclosure that should have been made.

Q In fact, Dr Wakefield, I am going to come back to that point at the end. Would you turn up pages 480 to 482 and to go back to the fundamental question in The Lancet paper, as is a fact, you did not declare the existence of the 1997 patent. Do you agree?
A Correct.

Q That patent, as we heard the other day, and is confirmed on page 474, was registered the beginning of June 1997. Correct?
A Correct.

Q In relation to the concept of a patent, and this patent in particular, what guidance was available to you at that time to assist in disclosure of matters such as this?
A Again, as before, precisely the same documents that were available to me in determining what constituted a conflict of interest in The Lancet.

Q I am not concerned with any reasoning which might now apply. I want to know, for the assistance of the Panel, what reasoning there may have been at the time which may have informed your decision making about the patent. In other words, what at the time did you view the nature of the patent to be and whether that is something ,alongside The Lancet paper as published ,that should be declared looking at the essential nature of the patent on the one and the paper on the other. That was a rather lengthy introduction, but I hope you understand the question.
A The answer is a very simple one: I did not feel that this should be disclosed, notwithstanding the fact that The Lancet paper had been disclosed submitted before the finding of the patent. My clear feeling at that time is that this patent would have been appropriately disclosed in a clinical trial that sought to determine the safety and efficacy of transfer factor in the indication of treating children with this bowel and behavioural disorder. That was my clear understanding at the time because, in those circumstances, it would have been a clear conflict of interest.

Q Would that obligation have fallen within the rubric at 616 of volume 2?
A Yes, it would.

Q Therefore, when you did not disclose the existence of the patent in The Lancet paper, were you conducting yourself honestly?
A Yes, I was.

Q I want just to deal with a further dimension in relation to the patent. Can you take volume 3 please, and turn to page 1116? This is a letter from you to the Editor of The Lancet on 23 June 1999, so about 16 months after The Lancet had been published.
A Correct.

Q “Dear Sir,

Further to my letter submitted yesterday, in response to the article by Taylor B et al” – and The Lancet reference – “I am writing to declare a potential conflict of interest that has just become current. If you decide to publish this letter, please would you include, as a post-script:

‘Dr Wakefield is a named inventor on an issued UK patent for measles virus diagnostics’.”

There are two background matters. Firstly, had you submitted a letter to The Lancet the day before?
A Yes, I had.

Q Was it directed to an article in fact by Professor Taylor?
A Yes, it was.

Q On the letter that you submitted, was there any reference to any potential conflict of interest?
A No.

Q What had happened in the meantime?
A After the publication of the 1998 Lancet paper, the temperature of exchanges, criticisms, allegations had elevated to the point where I personally had become acutely aware of possible conflicts or the need to disclose them over and above what I perceived to be The Lancet’s original requirement, and here I was tentatively disclosing the award of an unrelated patent, in this case a Crohn’s disease patent, the first patent that was referred to yesterday, in order to determine whether misinterpretation of The Lancet’s requirements were historically correct or not.

Q In the letter at 1116 you use the phrase that it has just become current. Can you just help the Panel with that, please?
A Yes. When you file a patent, there is a period during which that patent is a provisional filing, a year or more. In that time, you have to adduce further evidence in support of your claims or the patent falls away. If you can do that, then the patent is awarded and beyond that point it becomes a current awarded UK patent.

Q Following the letter that you submitted, as this letter says “yesterday”, what had happened in the meantime to cause you to write this letter on 23 June?
A I think on that day the award had been made, or I had become aware of the award having been made.

Q I want you now just to produce this document, please, which is pre-numbered.

(Document marked 1116aa circulated)

Was this the draft response to Professor Taylor’s letter in The Lancet?
A Yes, it was.

Q Is it your article?
A Yes.

Q That is the bottom right-hand corner. Did you send that draft to The Lancet?
A Yes, I did.

Q Is there any of your writing on that document?
A Yes. The corrections or additions to the text made at the top of the right-hand column on the right-hand side of the page and further down there is some underlining and some associated text, which I have put in.

Q In heavy ink?
A Correct.

Q Tell the Panel how does this come from you in the way it does now?
A This is a galley proof, which The Lancet send in advance of publication so that there is the opportunity to correct grammatical and typographical errors.

Q How did it come to you?
A I cannot remember – possibly by fax.

Q There is in fact a fax header, which is somewhat cut off from the top, but I am not concerned whether it is fax or otherwise for my purposes. At any rate, you received this document, did you not?
A Correct.

Q In this form?
A Yes.

Q Were your amendments on it when you received it or did you read them afterwards?
A No, these would have been amendments made to the documents sent to me.

Q On the bottom right-hand corner in different writing it says:

“A: We are not including your conflict of interest statement.”

A Correct.

Q Was that on the document when you received it back from The Lancet?
A Yes.

Q You can put that to one side. I should just ask you this. Was your letter in fact published in The Lancet?
A Yes, it was.

Q Did it include that conflict of interest statement that you had offered them?
A No, it did not.

Q In fact, the last section I want to deal with is very brief and to a certain extent you anticipated that I was going to deal with it. In relation to questions of funding and involvement in the litigation, in relation to those matters, tell the Panel, please, first of all: what did Professor Walker-Smith know, to your knowledge?
A Of those two aspects, the first was merely the disclosure in the correspondence that we saw yesterday in relation to JS of the possibility of the use of Legal Aid Board funding for the conduct of clinical investigation which was, in the event, not used. This did not apply to any other child.

Q And involvement in MMR?
A It was widely known, at least by our meeting in January 1997, of my agreement to act in the matter of the MMR litigation.

Q Did the Professor make any observations about the paper in those respects, give any advice, make any objections?
A No.

Q What about Professor Pounder, your line manager? What did he know about funding and involvement in the MMR litigation?
A He knew both of my agreement to act as an expert and he knew the details of the Legal Aid Board pilot study grant.

Q Did he see drafts of this paper?
A Yes.

Q Did he offer any advice, make any observations or express any objections to any aspect or apparent omission?
A No.

Q Professor Zuckerman: what did he know about funding and involvement in the MMR litigation?
A He knew the details of both, the full details.

Q We have looked at the correspondence relating to that, have we not, during the course of your evidence?
A Correct.

Q Did Professor Zuckerman see a copy of the paper at the proof stage?
A Yes.

Q Did he express any advice make any observations, any objections or suggest any deficiency in relation to any perceived duty of disclosure in respect of those matters in this paper?
A No.

Q In relation to the patent, was Professor Zuckerman aware of the existence and nature of the patent?
A Yes.

Q Did he express any objections or any observations or advice in relation to any apparent non-disclosure of the patent in The Lancet?
A No, he did not.

Q Who else knew about the existence of the patent and nature?
A Professor Roy Pounder and other members of the medical school, including Mr Bryan Blatch and Mr Tarhan.

Q In relation to drafts of the paper before publication, in respect of those who did see a draft, did anyone draw your attention to the need to declare the existence of that patent?
A No.

Q Therefore, Dr Wakefield, in relation to your handling of matters in terms of submitting this paper for publication in 1998, leaving aside what happened later on and we will come to that in due course, will you tell the Panel whether you conducted yourselves honestly or not?
A I conducted myself honestly.

MR COONAN: Sir, I have come to a natural break. For my part, you can see from the index that there is not now in volume terms a great deal left to cover. One of the next steps will involve the operation of this technology. I am rather reluctant, unless you wish me to do so, to embark on this now.

THE CHAIRMAN: This is an appropriate time to break. That is my first observation. My second observation is that, as we agreed earlier, we will be spending some time reading the papers submitted this morning, although we have seen them before. We will be looking at them in relation to the evidence and globally. That will take some time this afternoon. I concur with you in the view that this probably would not be the right time to try to embark on this technical activity this afternoon. I am quite sure that Monday would be the right time for that.

MR COONAN: I am grateful for that.

THE CHAIRMAN: I will ask Ms Smith how she feels about that.

MS SMITH: I am entirely in your hands, sir.

THE CHAIRMAN: Is there anything else?

MR COONAN: Sir, no, except to help you and your colleagues that I think we may be completing Dr Wakefield’s evidence late on Monday. It is possible it might trickle into Tuesday. That is to give you some shape to the timetable.

THE CHAIRMAN: In that connection, I know that the Legal Assessor may have something to say about the reading time.

THE LEGAL ASSESSOR: As you may have observed when the Panel was dealing with the witnesses for the General Medical Council, they needed time to go through their notes to prepare their questions. Members of the Bar representing various parties might like to consider my tentative suggestion that when the evidence in chief is finished of Dr Wakefield, there should be some time, possibly as much as a day, for the Panel to go through that evidence in chief prior to cross-examination from those parties to consider the questions they may wish to ask and then, when the parties have asked their questions, to see if they still have anything. By the time Dr Wakefield is finished, it is going to be two weeks of evidence. It would seem unwise to go straight into cross-examination without people having assessed all of that evidence.

MR COONAN: That is entirely sensible.

THE CHAIRMAN: Again, Ms Smith, have you any observation on that? It is obviously provisional advice at this stage. We will take this either on Monday evening or on Tuesday morning when we come to it. Do you have any observations in the interim?

MS SMITH: No, I have not, sir, save to say that it does seem to me to be eminently sensible to give you some time to digest what Dr Wakefield said before he is cross examined. Exactly how long you need, it may be appropriate to re-visit on Monday. I entirely support the concept.

THE CHAIRMAN: There seems to be agreement today on this matter. We will get on with some of the grinding work that we need to do this afternoon.

Dr Wakefield, we have now approached the stage of a weekend but you are still under oath and still in the middle of giving your evidence and therefore you are not entitled to speak to anyone about this case, including your lawyers and advisers.

MR HOPKINS: As an entirely practical point, because I know you indicated that the Panel may wish to read papers, does that mean we will have access to this room this afternoon?

THE CHAIRMAN: Having spoken to members of the Panel, there are some difficulties with travel arrangements as it is a Friday afternoon. Most members may prefer to take the papers with them and read them at their leisure. There is nothing very confidential about The Lancet papers. They are all published in journals and widely known to any member of the public. Although I cannot speak for every member of the Panel, as far as I know, most will take the papers with them.

Are there any further comments from anyone here? We will now adjourn and resume at 9.30 on Monday morning.

The Panel adjourned until 9.30 am on Monday, 7 April 2008

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