Thursday, February 2, 2012

Day 33 GMC Fitness to Practice hearing for Andrew Wakefield



Wednesday 5 September 2007

Regents Place, 350 Euston Road, London NW1 3JN

Chairman: Dr Surendra Kumar, MB BS FRCGP

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

Legal Assessor: Mr Nigel Seed QC


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


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


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

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

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

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


Page No


Examined by MS SMITH, continued 1
Cross-examined by MR MILLER 6
Cross-examined by MR HOPKINS 29
Re-examined by MS SMITH 34
Questioned by THE PANEL 37
Further re-examined by MS SMITH 46
Further cross-examined by MR MILLER 49

THE CHAIRMAN: Good morning, everyone. Ms Smith?

Examined by MS SMITH, continued

MS SMITH: Thank you. Good morning, Dr Davies. I would like to look at a table summarising the histopathology results in respect of these children. I know you saw this table yesterday and I would like to produce copies for everybody and for the Panel. I will explain what this table consists of. I think it will be C10. If we can call it Table of Histological Descriptions, C10.

THE CHAIRMAN: This “Table of Histological Descriptions for Lancet Children” will be C10. (Document distributed and labelled C10)

MS SMITH: If I can preface the question I am going to ask Dr Davies by telling you that there is nothing new in this table. All it does is set out, in a form that makes it easy to refer to rather than you having to go back and forth through the files, the evidence I took Dr Davies through yesterday. It has the child’s number, the description in the original histopathology reports that Dr Davies told us about yesterday that she either did or reviewed for the histopathology meeting. In the second column, where we have the notes of the histology meeting, it sets out the findings of that meeting. The third column is the only one we have not expressly gone to, which is the ultimate description in The Lancet paper. So you can see where the information comes from, would you turn to the Fitness to Practise, FTP, bundle 2, page 784.

THE CHAIRMAN: Ms Smith, sorry, I think C10 was the statement of Deborah Davies, so I think this will be C11.

MS SMITH: Thank you. I must be one behind in my list.

THE CHAIRMAN: If everybody could correct it, this Table of Histological Descriptions for Lancet Children will be C11. Sorry, I think this must be C12 because I have something for C11. The statement of Deborah Davies is C10 and the supplemental statement of Deborah Davies is C11, so this document in fact should be C12; apologies all round. This is now C12.

MS SMITH: If we could revert to FTP2, page 784, to remind ourselves so we are all clear, Dr Davies. This is in The Lancet article, The Lancet paper, which starts at page 783, at the top of that page on the right hand side we see the histological findings.
A Yes.

Q The table C12 sets out those descriptions down the right hand column?
A Yes.

Q Just so we are all clear, to recap on yesterday, those histological findings in The Lancet paper are the ones which were apparently assessed, as we see if we look in the left hand column on page 784, not by you but by Professor Dhillon, Dr Dhillon as he then was, Andrew Anthony and Dr Wakefield?
A That is correct.

Q The ones with which you were involved were the ones we discussed yesterday, the original histopathology reports on some occasions and the review of those, and the histology meeting discussions.
A That is right.

Q I think in your statement you deal with three cases in particular and I want to look at those cases in general terms. Running one’s eye down that table, at least to someone who is not a histopathologist, there appears to be differences between the initial histopathology reports and the description in The Lancet paper. If we can look at the ones you deal with in your paper as an examples of that. With Child 2, on page 2, we see the comment at the bottom of the report, I have read out the whole report, the comment says:

“The mild patchy generalised increase in inflammatory cells with lymphoid aggregates and follicles is not very specific but could be in keeping with low grade quiescent inflammatory bowel disease.”

Then we see the meeting in the next column and the clinical notes. The list for the meeting had “No comment”; the clinical notes at the Histology meeting were:

“Terminal ileum – no obvious inflammation. Enteric colonic series –↑ chronic inflammatory cells in mucosa some oedema on one section odd ? epithelial cell; marked lymphoid hyperplasia [with] some evidence of neutrophil infiltrate of crypt unusual to see such lymphoid changes in transverse colon. Rectum slight degenerate epithelium – collection of polymorph.”

That was the first histology meeting. In the next one we see the note which we know is from you, “Nothing abnormal detected”, and the reference “Mild prev”, which you told us described the previous findings to be mild.
A Yes.

Q We see in the final column how it was described in The Lancet as:

“Acute and chronic non specific colitis; reactive ileal lymphoid hyperplasia.”

That is the first one you refer to. If I can take you through them and then I will ask you questions. One can do the same exercise with all of them, but if one turns to number 8, you will see Child 8 and your report on the left hand side, with the comment:

“Minimal inflammatory changes which may be the result of operative artefact.”

and you have explained to us that operative artefact is the inflammation which may come from the actual procedure of the tissue being removed. Then you see the list for the meeting note, there is nothing abnormal detected. The histology meeting itself, the histopathology is described as “Normal” and then we see:

“Acute and chronic non specific colitis: reactive ileal lymphoid hyperplasia.”

as the description in The Lancet paper.

If we look at 9, we see:

“Large bowel mucosa showing prominent lymphoid follicles but no histological abnormality.”

Then the list for the meeting said, “Nothing abnormal detected”, and the histology meeting note says:

“No active inflammation. No crypt distortion.”

In The Lancet description we see:

“Chronic non specific colitis: reactive ileal and colonic lymphoid hyperplasia.”

We can do the exercise with all of them and I am very happy to go to any you want to go to, but those are the three you deal with in your statement. You told us yesterday that you had some concerns of time about the descriptive use of the word “colitis”, and you said that that, to you, meant active inflammation or a pattern of changes that suggested a specific diagnosis, and that it had not been your impression that such a pattern was identifiable in the pathology. To you, as a histopathologist, other than that description of “colitis” which you told us concerned you, do you recognise, in the description in The Lancet, any reflection of your findings or those of your colleagues in the clinical analysis?
A Yes. It does appear that whenever we have seen some active inflammation it has been also seen within the description in The Lancet paper, but, in addition, there appears to be some cases where active inflammation was not reported on the original histology but was seen by the three people involved in reviewing the pathology, in particular to ascertain any features on the review prior to publication. I would not be surprised that a formal systematic review taken without any clinical pressures may add – more features may be found.

Q When you say “without any other clinical work pressures”, what exactly to do you mean by that?
A That the histopathology reports would have been generated by myself and everyone else within a normal work context where you do not necessarily have protected time to look very closely, as you would do with a formalised review. I do not know how the three assessors reviewed the cases for The Lancet paper, but as you have seen how I myself reviewed the fifty four cases subsequently, it was done with a proforma where you record every minute detail. This is obviously far more time consuming than you would do in a generalised histopathological session.

Q Is what you describe as the minute detail something that you need to analyse and describe in this way in what you have described as your normal work context?
A Sorry, that to me was two questions, can you break that up.

Q You described to us your findings you said were in what you described as your normal work context?
A Yes.

Q You then said that is rather different from what you will get in a formalised review where you are looking for minute, or where you may have the time, to see minute detail?
A Yes.

Q What I am asking you is whether that minute detail is in fact a necessary component of your normal work context. In other words, when you are doing your normal work, clinical work, why do you not need that minute detail?
A Because if you are trying to identify, certainly something that you think is a novel observation, you would want every case to be looked at in this minute detail with proforma, so in every case that is looked at everything is recorded as being absent or negative. It is something that I would consider to be good practice with any histopathological based research material.

Q What you are saying is that these – and I do not think there is any argument about it – were research, this was a research analysis of the tissues, as you understand it, that was being done for The Lancet paper?
A Yes.

Q Yours was not a research analysis, is that what you are saying?
A The twelve – the children who I discussed at the Friday, if you like

Q These twelve?
A I am not sure I discussed twelve of them. Obviously I reported some of them. The majority I did discuss with the clinicians. It was within a working environment of a clinical pathological meeting making decisions about management, treatment etc. I certainly do not think they are substandard reports, but certainly suitable enough for what was being asked of the pathologists.

Q I should make it absolutely clear to you and indeed to the Panel as well that I am not suggesting for one moment that your reports were substandard in any way. I am trying to ascertain why there is a difference in the way they are looked at and you have said that, in the context of your discussions with the clinicians, it was relevant to the treatment of the children; is that correct?
A Treatment and diagnosis, yes.

Q They go together, do they not?
A Yes.

Q You have to have a diagnosis in order to decide how to treat, presumably.
A Yes.

Q Perhaps I may now revert to the question I asked you before. For those purposes, for the purposes of diagnosing and treating the child, did you regard it as being a necessary part of your job as a clinical histopathologist to go into what you have described as the minute detail that is in the research analysis in the The Lancet paper? Was it necessary in order to diagnose and treat the patient?
A No. I think there would be far less time and it would not … For routine diagnostic purposes, that level of minute detail would not have been necessary in the vast majority of cases.

Q I want to turn on to one last matter which relates to a separate subject arising out of The Lancet paper in relation to the ultimate retraction of the interpretation of the paper. You have told us that you had some concerns about the histopathology as it was reported and the steps you took in relation to your review. Were there any other concerns that you had after The Lancet paper was published?
A Obviously the media frenzy was not particularly pleasant but, in particular, I took no action until being further contacted by email by Dr Murch and this is when I had left the Royal Free and was at Addenbrooke’s in Cambridge.

Q What was the purpose of Professor Murch contacting you?
A To highlight a position of which we had been unaware in relation to the legal position of some of the children who had been written up.

Q When you say that you had been unaware of it, what was it that Professor Murch told you that you had been unaware of?
A This was done by email and I cannot quite remember if there was a phone conversation in addition, but that there was litigation being done … Some of these children were involved in litigation at the time of them being assessed within the full registration.

Q Did he tell you anything about the funding relating to the research?
A I do not recall.

Q You have said that he told you that some of the children were involved in litigation. How was that a matter of concern?
A Because of some of the temporal associations that had been highlighted within the paper, I think it would be fair to say that consciously or subconsciously a level of bias could be interpreted in the memory of people who were involved with possible litigation.

Q Who do you mean by that?
A The parents.

Q You say that you did not know about it at the time. Did Professor Murch convey to you how it had come about that there were children involved in litigation and there was this possibility of bias as a result?
A No, I do not recall.

Q Was it a matter that caused you concern?
A Yes because I was prepared to be party to the subsequent retraction to that aspect of the work as described in The Lancet paper.

Q We will now look to see that. It is in FTP3 at page 1210, the retraction document. I know that you know what it says, Dr Davies. This is just to remind everyone.

“We wish to make it clear that in this paper no causal link was established between MMR vaccine and autism as the data were insufficient. However, the possibility of a link was raised and consequent events have had major implications for public health. In view of this, we consider now is the appropriate time that we should together formally retract the interpretation placed on these findings in the paper, according to precedent”

and we see your name amongst those who were signatories to that retraction; is that correct?
A Yes.

Q Had you ever been involved in such a procedure of having to retract a scientific paper before or a part of it or an interpretation of it?
A Not that I recall, no.

Q Is it something you would recall?
A Presumably, yes.

Q Did you have anything to do with the drafting of the retraction document?
A I saw several drafts of this that was communicated via email.

Q Did you contribute to the drafts?
A I did. If I did, it would be no more than the odd word to alter.

Q As far as you were concerned, what was the central issue that made you think you should sign up to this document?
A Even in the original paper, although it said that no cause was found, it would appear that the reporting within the media had become quite out of hand and there were small bits being taken out of context from the paper. That negative aspect was minimised and it was having implications for the general health of the population.

MS SMITH: Thank you very much, Dr Davies.

THE CHAIRMAN: Dr Davies, as I said earlier yesterday morning, which does seem a long time ago, after Ms Smith’s questioning, there would be an opportunity for counsel for the three practitioners to cross-question you if they feel it appropriate and they are going to start now. Mr Miller is representing Professor Walker-Smith and he will be the first counsel to ask you questions.

Cross-examined by MR MILLER

Q Dr Davies, you were appointed to the consultant post at the Royal Free Hospital in November 1995, I think.
A Yes.

Q Before that, you told us that you had been at St Bartholomew’s as well but, between St Bartholomew’s and the Royal Free, did you have another position anywhere else?
A Yes. I do not have my CV here. I had been a consultant at Worthing District General Hospital.

Q Professor Revell, who has already given evidence, said that he thought you had been at Brighton before you came but it is Worthing just down the coast.
A Yes.

Q Was that your first consultant post?
A When you were at St Bartholomew’s, was that as a senior registrar in the early 1990s, I think?
A Yes.

Q And you had known Professor Walker-Smith there, not terribly well but you knew him and came across him professionally as part of the link-up between the histopathology department and the paediatric gastroenterology department.
A Yes. In particular, I would say that I had come across the pathology from the children with whom he dealt far more than I did with him because I said that a consultant histopathologist normally dealt with the meetings but I was very much aware of the type of cases which I would be involved in reporting as a senior registrar.

Q That would be in the position of the trainees we have seen at the Royal Free who were supervised or participating with a consultant.
A Yes.

Q At that time, this was part of your training. The weekly meetings would be run by Professor Slavin whose special expertise was gastroenterology.
A There was also a Dr Paul Richardson with whom I believe he worked very closely who also had previous exposure.

Q They were professor and consultant with great experience in gastroenterology and they dealt with the weekly meetings.
A Yes.

Q Except on occasions I think you deputised when they were not available.
A And another senior registrar. That is my recollection. I might have done one or two in three years.

Q You developed some expertise in paediatric gastroenterology as part of the routine reporting.
A Yes.

Q Obviously, if you had to present the cases for the meeting, that would involve demonstrating that expertise by going through and reviewing the slides that had been obtained.
A Yes.

Q Did you go to a specialist department at Worthing?
A No. That was a district general hospital although I acted as the main liaison pathologist for the gastrointestinal team there. I would like to add that, like other registrars at St Bartholomew’s, I had a rotation to St Mark’s Hospital in London which is a specialised colorectal disease hospital.

Q That is all it does pretty well, is it not?
A Yes.

Q It is a highly specialist hospital.
A Yes.

Q Is that mostly adults or is it adults and children?
A It would have been mainly adult but because of some of the genetic abnormalities, there would have been I believe some overlap with teenagers.

Q Before Professor Walker-Smith’s team arrived at the Royal Free, I think you have confirmed – and others have done so as well – that there was no paediatric gastroenterology department there.
A It was before I arrived there but that was my understanding, yes.

Q To that extent on the histopathology side there would not have been as much experience as there would have been at Bart’s, say, where there was a specialist unit?
A Yes.

Q For children – dealing with children.
A Yes.

Q When Professor Walker-Smith got to the Royal Free he sought to set up similar arrangements to those which had been in place at St Bartholomew's?
A That is my understanding, yes.

Q By that I mean weekly clinico-pathological meetings and also to have a nominated lead histopathologist consultant who would deal with those meetings, as Professor Slavin had done and Dr Richardson had done there.
A Yes.

Q He was quite keen to get somebody, and you ended up being the person who became for many years the lead consultant?
A Yes.

Q I think initially there was a lecturer there, or senior registrar, who set a system up, but then you took over as the lead consultant?
A I cannot answer for when I was not there, and I was not party to the initial discussions as to the requirements, if you like, from the paediatric gastroenterology department what they wanted from the pathology department. I do recall it being discussed at our histopathology departmental meeting from time to time, but I think it would be fair to say there was a little bit of political shenanigans, really, where it was my impression that some things had been promised by the Trust, with the implications of resources which was then not being delivered to the histopathology department. I cannot comment further upon that, but I believe Dr Dhillon, who had sizeable experience in gastrointestinal pathology himself had maybe taken a lead to begin with, but he obviously felt he could not give the time.

Q The person I had in mind was something called Dr Kitching who was a lecturer, I think, and a senior registrar?
A He was a senior registrar when I arrived. He was very able. He did deputise some meetings, I thought, for me, but it might have been that he had done some before I arrived.

Q Just to put it in context, there are bundles FTP1, 2 and 3. Would you look at FTP 1. It is at page 89c. Do you have an 89c?

Q FTP 1.
A No, I do not have an 89c.

Q I am sorry. It is a green page. Do you have that?
A Sorry?

THE CHAIRMAN: It is one of the green inserts.
A Page 86c.

MR MILLER: 89c, I have. There is an 86c as well. It may not have been put in by the witness.
A No.

Q It is just that Professor Revell looked at these documents earlier and he may not have put them in the bundle. (Same handed to the witness) 89c is a letter early on, which must have been just after you arrived. Can I just explain the system, Doctor. Documents have gone into these bundles from time to time and because they were originally paginated, they have been given “a, b and c” numbers, or whatever. In this case we have three that have gone in since. If you are looking to find the document in here, which you did yesterday, you will find that it follows the main number. Then, there are documents afterwards they are “a, b and c”. This is “c”. So “c” is a letter from Ron Shields, who is the Director of Operations.
A Yes.

Q To Professor Walker-Smith on 28 December 1995. This would have been just after you started.
A Yes.

“Peter Ravell”

who is your head of department –

“has provided all the information necessary for a statement of case to be put to the Trust Executive for another Consultant Histopathologist. I will be pursuing this during January and, in particular, whether the next appointment would have a specialist interest in paediatric gastroenterology, which is Peter’s [i.e. Professor Revell’s] preference.

Whether, or not, the post has paediatric gastroenterology as a declared special interest, it is expected that the histopathology department should provide you with consultant level support. I had understood that this was to be provided to you by Susan Davies who has now taken up post. I will review these arrangements with Peter Revell when I return to work on 8th January.”

That is the beginning. There is some earlier correspondence about it – about what had been promised to Professor Walker-Smith – but you appear to have arrived and been earmarked to provide that lead consultant role for gastroenterology, certainly so far as the head of operations is concerned.
A It is my recollection I volunteered. My job title at the Royal Free was Consultant Histopathologist with a special interest in diseases of the liver.

Q Right. Could you insert those pages, please, after page 89. It is “a, b and c” there, is it?
A Yes.

Q Would you put that bundle away and go to FTP 2. We may suffer from the same problem. Would you go to page 605aa, which is immediately before page 606. Is that there?
A “aa”, did you say?

Q Yes.
A I have 605a.

Q Do you have 605aa – letter of 15 August 1997?
A 605a.

Q We have added in another “a” because there was already an “a”.
A I have two pages which are different, both 605a.

Q We will go to the green one. It takes quite a long time to get through the system, because this is a letter of 15 August 1997, almost two years after the one we have just looked at. Again, it is from the Director of Operations, but it is copied to you, to Professor Walker-Smith.

“I write further to our discussion of a couple of weeks ago which was preceded by discussions that I had with both Susan Davies and Jim McLaughlin.

I am happy to confirm that Susan Davies is the identified Histopathologist to provide a lead for the Paediatric Gastroenterology service and it was pleasing to hear your acknowledgement of the service that she and the Histopathology Team have provided. Obviously, for the sake of continuity of service it is important that there is more than one person providing the service but Susan is happy to be identified as the Lead Histopathologist.”

With a previous witness, we traced the series in the correspondence, but that looks to be the end product, almost two years after it had been mooted. It looks as though at that stage it is formal that you are the Lead Histopathologist. In fact, you carried on in that role, I think, up to the time you left and went to Cambridge.
A Yes.

Q Presumably from your experience at St Bartholomew's and subsequently when you got to the Royal Free you could see the sense in having a nominated lead at consultant level to provide continuity and an overall view, bearing in mind that you were seeing quite similar conditions going through over a period of time?
A Yes. There has been a trend within histopathology in general, with pathologists becoming more and more specialised. So this would be an example, really, of good practice, I would say where clinicians do need to have a point of contact within the department and also for pathologists themselves to increase their level of experience and expertise and also know some of the children and the conditions, some of which are very rare, some of which are very difficult to diagnose and often from the list you see that they are follow-up cases. These children were not only seen once; they were kept within some level of care for some time.

Q You say this is early. This is 1995, but of course it had been in place in the early nineties when you were at St Bartholomew's as a senior registrar?
A Yes.

Q Presumably you could also see the close collaboration between the paediatric gastroenterology department and the histopathology department represented a necessary and high standard of care for the children – this collaboration which meant that one was in one place and one in the other was pretty important for the care of the children, was it not?
A I think so, yes.

Q As you described it, there is a laboratory element to it which involved all of the pathologists as part of a rota, where they would be looking at the slides but as far as the meetings were concerned, that brought them two aspects together – the pathology side and the clinical side?
A Yes.

Q And at the weekly meetings, the three consultants used to attend subject to other commitments. When I say three consultants, I include Professor Walker-Smith in this.
A Yes.

Q They used to attend as many meetings as they could, together with the lecturer/senior registrar and, indeed, the latter would be presenting the clinical aspects of the cases, about which you would have had only the scantiest of knowledge before the meeting?
A Yes.

Q Really, Dr Davies, these weekly meetings were a vital part of the care of each of these patients, were they not, because out of them would usually come a consensus view for each patient, putting all aspects together, which would inform the diagnosis and certainly assist the management of that particular child?
A Yes. They were working meetings where all information was collated in terms of the state of the understanding at that time for each child.

Q That is the point, is it not, it was not just, “We’ll have a general chat about what cases we have had this week.” These children were nominated by the gastroenterology department who sent you the list, so it was concentrating on each child on that list?
A Yes. They would all be discussed in turn.

Q And realistically it would not be possible, would it, to provide a proper level of care unless you had something like that in place? You needed to have that close contact and discussion at the time that the child was being seen so that decisions could be made for the management?
A Yes. I might add further, that although people think histopathology, you look down a microscope and make a diagnosis, you can see morphological features but be able to generate a helpful and sensible histopathology report very much depends on adequate and decent clinical information. This is true in all aspects but in particular medical aspects of histopathology in which I would include gastro-intestinal disease, and my other special area of interest is liver disease. This is an example of good practice which is used in many institutes now.

Q Presumably, just taking up that point, you look at the slides, the slides are obtained from tissue taken at the biopsies.
A Yes.

Q Then they are stained in order to be able to identify the pathology.
A Well ---

Q They are cut, sliced.
A --- I mean, it is cut so fine it is less than a piece of tissue paper, and it is transparent, so unless you put stains on, you cannot actually see the tissue.

Q So you see that and you form a view about it, which is what the original pathologist does when he produces a report, but it may be that, and I suggest probably was, the case that when you hear about the clinical picture and the colonoscopy, then you may say, “Well, that actually falls into place. Perhaps that is more important than I thought it was at the time”?
A Yes.

Q Presumably, and I approach this delicately, if I may, there was a learning curve for all of the histopathologists at the Royal Free in view of the fact that there had not been a regular diet of paediatric gastroenterology cases before this unit moved. So experience grew and expertise grew at the same time?
A Yes, I think that is fair.

Q As I say, I approach it delicately, but would that apply to you as well?
A Yes, very much so.

Q You learn more about children’s bowels and problems afflicting them as you gain more concentrated experience over the years?
A Yes.

Q That would particularly be so, would it not, in relation to what I think you described as subtle abnormalities of the bowel which do not stand out as being clearly inflammatory bowel disease?
A Throughout the GI tract. I certainly learnt, for example, in children’s duodenal biopsies, you have to treat them differently from the adult, where there are questions like cow’s milk protein sensitive enteropathy. I think it would be fair of me to say I was a little sceptical about making that diagnosis until, within our Friday meetings, I was shown other features from electromicroscopy, et cetera, and I developed an understanding of how little changes did make a big difference to the management within the paediatric framework.

Q Some might not be, or become, quite as expert as you. The system as it operated involved a rota, which we have had explained to us by Professor Revell, which meant that you did not have only one person reporting, and so everybody took it in turn to report on anything that came in from whatever source, and that would be in some cases a consultant on his or her own, in other cases a senior registrar under the supervision of a consultant?
A Yes.

Q What they were doing was routinely reporting, which you yourself did on occasions. They were not involved in the next stage, which was the review for the weekly meetings, which was something which you mostly did yourself as the lead consultant.
A That is right.

Q So others might see rather less than you would overall because of your position?
A Yes, and can I add at this time, regardless of whether or not supplementary reports were issued on a variety of different conditions within these children, I have several recollections of feeding back after the meeting to other consultant histopathologists, where I thought there had been some subtle differences of interpretation, and discussed it with them further.

Q Right. That is regardless of whether or not an actual report was generated?
A An actual supplementary report, yes.

Q Now, on the clinical side, although I suppose it is not technically clinical, Professor Walker-Smith was very experienced and very good at identifying both growths and subtle abnormalities on the slides, was he not?
A Yes. In the meeting the images from the microscope are projected on a screen, and so he would have had many years of experience of seeing all of these different types of histology.

Q The whole point of having them on the screen was that everybody who felt that it was appropriate could express a view if they felt that there was something – the mere fact they were not histopathologists did not mean that they were not entitled to say, “Well, what about that or what about that?”
A Oh, absolutely, and often it was a teaching focus as well, because there were more junior clinicians there as well, and pointing out features, but, yes, there could easily be debate about some cases.

Q Can I just then ask you about inflammatory bowel disease.
A Yes.

Q Inflammatory bowel disease is or was or used to be taken principally to mean Crohn's disease and ulcerative colitis?
A Yes.

Q So when one talks about IBD, then generally people meant that as ulcerative colitis or Crohn's disease, which were the main inflammatory bowel diseases which you encounter.
A Yes.

Q Clearly, it would be important not to make a mistake, if it was possible to make a mistake, about the identification of one or other of those because of the implications for treatment.
A Yes. You are potentially making a diagnosis that might affect the person life long and require quite potent treatments.

Q There are quite different treatment approaches for Crohn's disease and ulcerative colitis, are there not?
A It is my recollection, certainly at that time, they were treated differently.

Q I think that, in terms of Crohn's, quite often enteral feeding was involved or was used?
A That is only my understanding from hearing the clinical debate at the time, because I myself as a pathologist do not prescribe any treatments.

Q No, but it would follow from the general discussion at the meetings that, you know, if there was a diagnosis made, it might lead to treatment of a particular type. I mean, I am not asking you as an expert, it is just that your recollection is that it would have an effect on treatment?
A Indeed. It is my recollection that someone like Professor Walker-Smith would actually make the decision at that meeting on occasion to choose which appropriate treatment pathway a child received.

Q We do see sometimes in the reports a phrase like “Does not amount to a diagnosis of inflammatory bowel disease”.
A Yes.

Q Which would certainly be the case if Crohn's or ulcerative colitis had not been identified, then clearly you would not find that as a diagnosis. It does not mean that there was not something there which was not Crohn's or ulcerative colitis.
A I believe that is one of my reports, and, like I said, a histopathology report depends on what you see down the microscope, the clinical information, and also specific questions are asked on occasion within the clinical details, and if the clinical details included “Could this be inflammatory bowel disease”, or anything else, I, as a general trend, would answer “Yes” or “No” in relation to this question.

Q By “inflammatory bowel disease” what would you mean?
A The idiopathic ones, namely ulcerative colitis or Crohn's disease, so the interpretation of my histopathology report like this says yes, there are some abnormalities, but this is insufficient, or too non-specific to suggest this definite diagnosis of inflammatory bowel disease and the natural consequences that that entails for the child.

Q I mean, that is the important point, is it not, because if you are either making or not making a diagnosis of Crohn's disease or ulcerative colitis, I mean if the position changed, for instance, if there was either a report that it was, or a discussion at the meeting which led to the fact that it was not (whichever way it is), you would need to generate an additional amended report for that because of the consequences of a change in diagnosis?
A Yes.

Q I think you said in relation to one or other that you had a duty, is it with Crohn's, that if it was diagnosed there had to be a report to the central---
A I think it was a diagnosis of any new inflammatory bowel disease, whether it be ulcerative colitis or Crohn's, but again that is a clinical issue.

Q Right, but it had that implication as well, that it had to be reported?
A Yes.

Q On that basis, if the original report did not reflect what was eventually considered to be the diagnosis, it would need to be amended?
A Yes, and also there is a sort of holding category between ulcerative colitis and Crohn's disease called indeterminate or equivocal colitis, where you think it is inflammatory bowel disease but you are not sure exactly which disease pattern it best fits, and that would be also another occasion where I might suggest one more than the other, depending on my experience, and generate a supplementary report at such a time.

Q On the other hand, if the consensus view at the end of a clinicopathological meeting, although different from the report, was not significantly so, and did not impact on the future management or care of the child, an amended report might not necessarily be generated?
A Indeed.

Q Now, you were a named author in The Lancet paper which was published in February 1998, but I think it is important to make it clear, and I think Ms Smith dealt with this in general terms, but you were involved as an author because you had been involved in the clinicopathological meetings which had involved reviewing most, if not all, of these twelve children?
A Yes.

Q As well as debating the pathological and clinical findings at those meetings, and because you had been involved in the original reporting of some, a minority, of the twelve, and that is why you there as an author?
A Yes.

Q I think, again, because there are a large number of authors, each of whom were doing different things, that would be the extent to which you would be involved in any paper that came out of this, just simply in your diagnostic role as the pathologist who either originally reported or led the discussion from the histopathology point at the weekly meetings?
A Yes. I would put myself as a minor author within this regard.

Q The only difference between you and, say, Dr Crow, who was another consultant, was that you had this sort of overarching responsibility to deal with the weekly meetings, so in fact you had contact probably with all twelve of the children who were reported?
A That is possible, yes, and can I suggest that a lot of the terminology that the registrars were writing in the notes appear to be what I was saying at the meeting, not necessarily what was on the report.

Q That is a very important point, that if there is a note of the meeting, it may well be that it is the end point note, in other words it follows a discussion at the meeting and is noted at the time by the registrar.
A Yes.

Q We have heard from Dr Casson, who was one of the senior registrars, he is named in the paper and we have heard the role that he played, and others in the same way, but that is what you were doing and it was essentially arising out of the service aspect of your position?
A Yes.

Q I think it is a minority, it will be in the table, but I think you were involved in five, possibly five, of the original reports, and then you were involved in the one amended report that we have got, Child 10, which was Dr Jarmulowicz to begin with, and then the two of you for the amendment.

Can I just ask you about the lists for the meetings. You have produced a number of lists which contain most of the children on them.
A Yes.

Q So I do not want to go through each of these because it means turning up a bundle for each one, but if we could just take a couple of illustrations. If you look at Child 7 in the Royal Free, page 150a, and if you could also have open the Royal Free notes for Child 2, page 270a. These are just illustrations because you have produced all these lists and I want to get it so we can see what we are dealing with. If we look, first, at 150a for Child 7, it looks as if it has been faxed from the Department of Paediatric Gastroenterology on the 29th, which would be the Wednesday
A Right.

Q if it is a Friday meeting because the meeting is on the 31st. There is a list of children. By definition all of them would have to have had endoscopy of one sort or another unless they had been involved in a resection, in which case there might be tissue from surgery, but most of them would be as a result of endoscopy either after or before colonoscopy?
A Correct.

Q Otherwise you would not become involved as a pathologist. So you get a list in advance of the meeting with these names on it. It is your job, if you are going to be taking the Friday meeting, to take up the slides for these children, all of the children, review them and be in a position to present the pathology at the meeting and to discuss what the findings were?
A Yes.

Q Some of these will have brief, as what you have described, aide memoire, notes on the side which helps you to differentiate between Child A as against Child B because, as you say, if they all have the same pathology you might not remember which is which. This is not intended to be a final diagnosis, this is what you think, having seen the slides, before you have had the discussion?
A That is my recollection. Certainly later on in time I did that. The earlier lists, as I say, I cannot recall always if I wrote before or during the meeting.

Q There may not be a pattern, but sometimes we see on the right hand side, to the right of the far right column, there will be something there and then if something has arisen during the meeting it may come in in the body of the list itself. Certainly, if you are looking at the first two on that list, in the middle you appear to have written something which looks like something more on the clinical side than just something that you have seen from the slides?
A Yes.

Q The point that I am trying to discuss with you is that this is a list which is routine that would be, with a greater or lesser number of children, happening almost every week.
A Yes.

Q Holidays and things you may not have been having them, but the idea was to have these meetings every week?
A Yes.

Q These are all children with some sort of bowel pathology, gut pathology, which has required endoscopy?
A Yes, although I think it is fair to say they had some kind of symptomology of clinical suspicion which have been investigated.

Q That is right, the clinical symptomology has led to an investigation which will either be upper endoscopy or a colonoscopy at which there would have been taken biopsies from various parts of the bowel. That is what you are reporting on?
A Yes.

Q This would be routinely weekly, and each of these children would be patients at the time, probably having been in patients for the procedure, and the purpose was to discuss each child and, if possible, come to a diagnosis and treatment options or further management options. That was the whole purpose of it?
A Yes.

Q We can see from 150a, two of the twelve who appeared, whose cases were reported in The Lancet, were on that list?
A Yes.

Q But all the rest, we know they were not reported in The Lancet, they were other patients with other bowel problems?
A Yes.

Q If we go to 270a on which Child 2’s name appears for the second time, because there had been a previous visit, this is after the enteral feeding period. He is one who was subsequently reported, but the rest, again, are in the same category of other children who are being routinely investigated?
A Yes.

Q From the list that you produced for the Panel, and I think you have all the lists for a period from 1996 through to 1998 or 1999 ---
A I think it is 1999.

Q --- certainly 1998, we can see that the children who subsequently ended up being reported in The Lancet are very much the minority. The one we have here is two children out of fifteen at page 150a, one out of six, and if we look through all those lists for the ones who were ultimately reported, you would find that it maybe be one out of five, six, ten, eleven, who have eventually became part of The Lancet paper, but the rest were just being investigated and treated in exactly the same way.
A Yes. As you have seen from these, it would be rare to get two children with autism and the bowel investigation.

Q As you say, we did go through the list yesterday, but it is a tedious business to go through it again, but in due course we may have to remind the Committee of what they are. In most cases it is one out of between six, I think, or between five and fifteen children being discussed on a weekly basis. These were all only the ones which would involve these children. The children with autism and you have explained how it is that you became aware that they did. In some cases it said on the request for histology that they did have autism or query autism spectrum. They would have been approached, as far as you were concerned, in exactly the same way as the others, the ones who did not have autism, the serious majority from the others?
A Yes, they were discussed in exactly the same format and they were reported in the same way. The same amount of time was spent on them in the generating of the report and the discussion.

Q At those meetings there was no distinction between autism child 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 as we see them now and any other children who were being discussed?
A No.

Q You were reporting on these children and all the other children and reviewing the histology as part of their NHS care?
A Yes.

MR MILLER: Would that be a convenient point to have a mid morning break?

THE CHAIRMAN: I think we will take twenty minutes for a mid morning break. It is 10.55 am, so we will resume again at 11.15 am. Dr Davies, you are still under oath and still in the middle of giving your the evidence so please do not discuss this.

(The Panel adjourned for a short while)

MR MILLER: I only want to ask you a few questions about the twelve cases because I assume you cannot say now what you thought about them when you either reported or reviewed their cases, because they were just part of a very large number of children passing through the Paediatric Gastroenterology Department for whom you were dealing with the histology?
A Yes.

Q Do I understand it correctly that, at the time, that is when you were either preparing a report or reviewing for the purpose of the meeting, you did not identify any of these cases as being future Lancet cases?
A No, they were never discussed in that way either as I recall.

Q Nor indeed any special category, they were just part of the routine of the department?
A The only unusual thing would be the clinical details, which include autism often, was relatively novel to me.

Q Essentially they were just part of the your NHS diagnostic workload?
A Yes.

MR MILLER: I wanted to use Child 2, if I may, for a limited exercise so that we can understand the system from your position in the histopathology department. With some trepidation, can I hand up two diagrams on one page. We have spent several weeks banding these terms around, but if I tested everybody on the their knowledge of the gut, some anyway would be found lacking, and I would like, perhaps with this witness to identify what we are talking about because we have not seen any guts up to now. What D number?

THE CHAIRMAN: This is D4. (Document distributed and labelled D4 ).

MR MILLER: From the reports that are generated from your department, we see it is not just a question of a specimen being number I to V or VI, it comes from designated areas which are contained within the report.
A Yes.

Q We tended just to read the reports, but they show in each case where the sample has been taken and then, presumably, that reflects the pathology in that particular part of the bowel. Perhaps if you look at the top diagram first. We are talking about colonoscopy and working up from the bottom. The rectum, then there is the sigmoid colon, the left colon, transverse colon, right colon and then the ileum which comes off just above the caecum.
A Yes.

Q There is a bowel there, and when there is reference to terminal ileum, I do not know whether there is in any of the histology reports, it would be that part of the ileum which has been sampled?
A Yes, which has been accessible via the colonoscope.

Q When you translate that to a report, you will see that that comes from – if you look at page 264 in Child 2’s first report, do you have that report received on 2 September?
A Yes.

Q It is working in the other direction because they have reached the ileum, so specimen I would be from the terminal ileum, specimen II from the caecum, which is the end of the bottom of the colon. Is that right?
A Yes.

Q Working back round towards the rectum, the third specimen is the ascending colon, which is the right colon, transverse colon is next, sigmoid colon is the next and then the rectum, so you have a full hand?
A Almost, or in this case no biopsy was taken from the descending colon.

Q If you go to the sigmoid but miss out the descending colon.
A Yes.

Q This is a sort of pattern for most of these reports. It identifies where they come from and reports the pathology in that part?
A Yes, it is totally routine for the generation of multiple biopsies from different sites. My understanding of all children having colonoscopic examination, the terminal ileum, if they got into it, there is a problem sometimes with that, and if there are focal lesions they may also be samples. We use the Roman numeral system to identify the individual specimen, but these themselves, the sites, would have been designated by the endoscopist by writing that on both the request form and the individual pots of the specimens.

Q It may be that they would want to have everything but they would say, “We need you to analyse or report upon what we have obtained from these sites”?
A Yes.

Q So you know before you begin to examine them where they have come from and then you report on them separately for each site?
A Sometimes, if the features are similar from each site, people will amalgamate those specimens in the reports.

Q Quite often we have seen along the way that the ileal site is dealt with and then the colon is dealt with as II to VI or II to V, or whatever it is, II to IV, and a general description is given of all the samples from the colons.
A The terminal ileum would always tend to be separated off because that is the end of the small intestine.

Q Turning over the page, there is no other reason for choosing this patient other than illustration A of where the sampling was done and B the second part of the illustration shows the bowel in its various layers, I hope. You may be upset by this, that is too much of a Mickey Mouse approach to it.
A It is just for clarity. The diagram here talks about the mucous coat where it is now more accepted terminology, certainly in European practice, to call it mucosa coat, so where you see “mucosa” throughout all the reports, it is the equivalent on our diagram of the mucous coat.

Q We have the lamina propria of the mucosa; is that underneath?
A It is the supportive specialised connective tissue that is holding, if you like, the work parts of the intestine which are the intestinal glands or crypts. They are the epithelium doing most of the function within the intestine, but it is sitting in this specialised connective tissue which is called lamina propria within the intestinal tract.

Q We see that frequently referred to in the reports.
A Yes.

Q In fact, on page 265, under I which is, I think, from the terminal ileum, is it not?
A Yes.

“Fragments of small bowel mucosa with mild chronic inflammation within the lamina propria.”

A Yes.

Q Granulomas are a distinct entity, are they not?
A They have a very important significance within the assessment of bowel disease in particular.

Q Would you look for granulomas as you did these …?
A It is often an important negative that I put in all reports but, in particular, one would be interested in the ileum in the assessment of possible Crohn’s disease. Its old-fashioned name was actually regional ileitis as the first description because this can be diseased and the colon itself can be normal, so the presence of a granuloma in a terminal ileum biopsy is a highly significant finding.

Q And it would lead you in the direction of Crohn’s disease?
A There are obviously differential but, in the right clinical context, it would be a very strong supportive histological feature.

Q On page 265, would you look at III, IV and V. Again, we have,

“… patchy increase of chronic inflammatory cells within the lamina propria and occasional prominent lymphoid follicle with a germinal centre …”

Would you help with the lymphoid follicle. Was is that as a description from a histopathologist?
A You can see that it is diagrammatically indicated on that figure as a solitary lymphatic nodule. This is something that is recognised down the microscope as a collection of chronic inflammatory cells, predominantly lymphocytes and other cells which have a structure to them, they are not just an ad hoc collection of cells, and this is important within the cellular trafficking of inflammatory cells with the outside world and the body because of course the lumen of the intestine is full of antigens. It would count as the outside from the body’s point of view and so an important line of defence is the immune system with all the inflammatory cells with particular lymphocytes. So, a normal finding are these specialised lymphoid follicles scattered throughout the intestinal tract within the mucosa.

Q My last point on that is, what is the germinal centre?
A When the immune system appears to be stimulated for some reason, then there are morphological changes to this lymphoid follicle which is identified down the microscope as what we call a germinal centre. The lymphoid follicle tends to increase in size and the cells themselves are turning over more rapidly, they are more active.

Q There are two other matters that I want to ask you. At the bottom of that III, IV, V paragraph where it says, “mild crypt distortion” and to the left-hand side of the illustration which says, “intestinal glands (crypts)”, I appreciate that you are not looking now at a slide but is it related to that part of the …?
A Yes. Normally these are, if you like, an elongated U-shape or a test-tube shape to the normal crypt but, when there is significant inflammation and often a mark of previous significant inflammation, this neat architecture is distorted.

Q This is the final point on this. Certainly in one if not more of the reports that we have seen, there is a reference to the fact that the sample has in it muscularis mucosae which we can see halfway down that split diagram.
A Yes. Sometimes it is present in biopsies but not always, but it does show that you have, if you like, a decent sample of the mucosa because the muscularis mucosae is the limiting edge to the mucosa to then below the submucosa.

Q So, it just means that the sample has come from deep enough to get to the muscular ...
A Yes. It is a soft feature but sometimes if there is an inflammatory process involving the muscle, that can also give you an indication of pathology.

Q Thank you. Would you put away the bundle for Child 2 for the moment but keep it to hand because I want to come back to him in a while and the diagram, please. I want to ask you about Child 4, so would you take up the Royal Free Hospital notes for Child 4. If you have the bundle for Child 7 out, you may put that away. With Child 4 on page 13 – and this is in the clinical notes, a note which has been identified by Dr Casson – it is dated 4 October and it is headed,

“Histology meeting

Ileum - dense lymphoid pattern
- no acute inflammation
- normal architecture;

colon - prominent lymphoid follicles
- no active inflammation.”

There is nothing said about the rectum and

“No granulomas”.

That is dated the fourth. The histology report for which you were shown as participating does not appear to have been issued until 7 October. It is in the same bundle at page 33C. The only date, apart from the fact that it has been printed on 30 August of this year, is where it says, “Specimen Received: 30/09/96” and “Report Issued: 07/10/96” and this is a report that has come off the histology department computer; it has not been signed up by you, has it?
A No, it would have been the responsibility of Dr Rees as the trainee with me to finalise the report.

Q I think you comment that this has been obtained quite recently – you exhibited it to a later statement – and it came from the histology department.
A That is Child 10.

Q Thank you. From its date, this copy was printed on 30 August of this year but, in any event, if it says on it that it is issued on 7 October, the original date on the left-hand side, that would imply that it was not available on 4 October, would it not?
A No, I would interpret that slightly differently.

Q I am just asking a question.
A Am I right in that this child does not appear on any of the lists that I had for 4 October?

Q Just give me a moment. (Pause) I think you are right. I do not think we have seen that anywhere.
A There are two things. For me to be “(P)”, I have definitely seen the case. It was issued on 7 October which presumably would have been a Monday and discussed at the previous meeting which was a Friday lunchtime of 4 October. It is quite possible that the report was generated at the last minute ready to be discussed at the meeting but because it was with a register, it would have needed a secretary to type the finalised report before [it was] authorised by Dr Rees. To me, it would make sense that, on the following working day, the finalised report was authorised.

Q I want to explore, not in any great depth, but we do at least have a date for the meeting noted there and that information, which has been set out in summary form by Dr Casson, would have come from somewhere because it has the histology details in it. So, it would either come from general discussion, his note of that discussion with you leading the discussion in the histology, or there was a report of some sort which did not find its way into the notes. It seems to be one or the other.
A This is a copy, is it not?

Q Yes. This arrived, as you can see from the date, quite recently.
A I cannot make a comment as to why it is not in the records but I can understand why a case would have been completed to a level of being able to present it at a Friday lunchtime even if the finalised report was done the following day.

Q That was my point. There is enough here from your review for Dr Casson to get an account put in the notes of the findings. So, you must have reviewed the histology anyway in that case. The only question mark is whether or not there was a formal report by that stage in the notes and we have no way of knowing. Clearly, what it does demonstrate is that there was sufficient discussion at that meeting for the registrar to have noted what the findings were in various parts of the gut.
A Yes.

Q This is not a criticism of the system, it is just trying to find an explanation about where he would have got it. The explanation would be at the meeting.
A Yes.

Q You can put away Child 4. I want to ask you about the publication of The Lancet paper and you will need to have FPT2 in front of you. Before we get to the paper itself, you say that you received in draft a copy of the draft of the paper that was going to be presented, so by that stage you would have been aware that there was going to be a paper.
A I assume that I saw a draft because that would be normal practice of any authorship involved in any publication.

Q Would you turn to page 616A in that bundle, FTP2. This is a document which one of the previous witnesses has looked at already. It is a letter sent from Dr Wakefield on 8 October 1997. It has the heading of the paper and then it has to the various people who are set out underneath it, I think in the order in which they eventually appear in the paper itself. The only reason there is a tick by Professor Walker-Smith is that this has been introduced to the hearing by Professor Walker-Smith. Clearly, you are shown on there as having been sent a copy,

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

So, it is likely that, at about the same time as everybody else, certainly a version of The Lancet paper would have been sent to you.
A Yes.

Q Would you turn forward in that bundle to the paper itself which is close to the back – it starts at page 783 – first of all, just reverting back to the letter from Dr Wakefield, you would have seen that Dr Anthony and Dr Dhillon were also sent a copy of this and the list of the proposed authors was there. You would have seen Dr Anthony and Dr Dhillon involved in the paper in the way that you have been taken to it by Ms Smith earlier. They are identified as pathologists involved in the work which led up to the paper.
A Yes.

Q We have seen Dr Dhillon involved in providing the routine histology reports in two of the cases as we went through yesterday, one on his own and one, I think, participating with one of the registrars. From the text of the paper, you would have seen that he, Dr Anthony and Dr Wakefield, were involved also in what you would have seen presumably as the research aspects of the paper.
A Yes.

Q Because, if we look at page 784, under “Histology” it identifies what you did although not perhaps in full detail but also what they did and the type of assessment that they carried out.
A Yes.

Q All tissues were assessed by those three, so you would have known that, apart from the service aspect with which you were involved, there obviously had been a research aspect which had involved other people within your department.
A Yes.

Q And that would not have surprised you.
A No.

Q Indeed, I think some of the meetings either Dr Dhillon or Dr Anthony had been asked to attend. I think it was one of earlier ones; right at the beginning I think we saw Dr Anthony’s name.
A Dr Anthony is on the routine fax distribution list, I believe.

Q I think that he is on it from time to time. The first one you were taken to I think he was on but I am not sure that he continued to be. This would not have made any difference to you because your part in diagnosis was very different from anybody else’s part in later analysis.
A Yes and anybody who was interested was free to attend these meetings. It was a slightly different group on each occasion.

Q Dr Davies, do I get the impression that you were disappointed that the hypothesis which was set out in the first paper, that the gut and neurological problems were linked, was overlooked as a result of other aspects which the media got hold of? I am not sure that I have explained that very clearly. As a doctor, were you disappointed that not enough coverage was given to what might well have been a new phenomenon that was being described?
A “Disappointed” is one word, but yes, I think the idea that something novel has been observed in a handful of examples needs being spoken about in a public manner, to then lead to further investigation, to any assumptions of any hypothesis, how prevalent something is. It is a starting point. And the coverage was very much one of the paucity of intelligent debate, really, when there is a complex scientific evidence-based observation or an evidence-based paper.

Q I think not the paper itself, but the findings, the new syndrome (if it was a new syndrome) was rather overshadowed by the interest, particularly media interest, in the possible link with MMR?
A Yes.

Q So the medical aspect was rather overshadowed by that?
A Yes.

Q Lest we think that we are dealing with just twelve children, you continued to provide the diagnostic service, which you have described, to the department of paediatric gastroenterology, on the same basis for many years after 1998?
A Yes.

Q And it went on. There is no difference between it after 1998 and what it was before. The same types of children were coming in with bowel problems of one sort or another?
A Yes, including a small cohort of children with autism ---

Q Exactly.
A --- who had symptoms relating to the intestinal tract.

Q Yes. That was my next point; that within that number that came, right up to the time at which you left, there were children who were identified as being within the autistic spectrum, and they were investigated as you do not have described?
A Yes.

Q Alongside many, many, many others who were not autistic but were equally investigated exactly the same way ?
A Yes.

Q And they were all treated or their cases were approached in the same way, whether they were autistic or not, by the gastroenterologists and by the histopathologists?
A Yes.

Q And indeed, you were a co-author, or contributed in the way in which you have described, to subsequent papers which reported the suggested link between neurological problems and gut disorders?
A Yes.

Q Just a couple of final points. Terminology: again, I do not want to go in great depth but there appears to be no black and white in this part of medicine, in which I include both for the purposes for this case – paediatric gastroenterology and histopathology – in terms of the terms that are used to describe what is seen, either histologically or colonoscopically?
A Yes.

Q Histology is not an exact, measurable, scientific test?
A Correct.

Q When you say “We found that”?
A Yes.

Q And there is, as I say, no absolute consistency in terminology. Indeed, as between the clinicians and the histopathologists, different terms might be used because would be involved in diagnosis leading to treatment. Therefore they may be using descriptive terms which would have a bearing on what treatment is put forward?
A Yes. And also pathologists themselves use slightly different terminology, depending on their own experience and where they have been trained.

Q There may also be differences between what might be different for routine diagnosis, which is what you were effectively involved in, and words used to describe fine details in a research paper?
A Yes.

Q That is from the histopathology point of view. Could I ask you to look at Child 9’s notes, please, at page 48. Under the microscopic description, specimen I, which was from the terminal ileum:

“Small bowel mucosa showing no histological abnormality”

and specimens II to VII, which is the rest, going to the rectum:

“Large bowel mucosa showing prominent lymphoid follicles but not histological abnormality.”

The Lancet paper, as was pointed out by Ms Smith this morning, reports this child as having – you accept it is on that table – chronic non-specific colitis, reactive ileal and colonic lymphoid hyperplasia, but any difference or perceived difference here is effectively one of words, is it not? There is a grey area between the diagnosis that is done, as you described, as part of routine histology and words used to write up the fine details of a research paper?
A And also one gets a much clear idea of patterns of diseases when you centralise your review in time and place. If you look at ten cases all of the same type of condition, against a set proforma, you will end up with a much clearer idea of, say, the significance of features. For example, this is a very short, terse report. It is a reflection of Dr Maddox’s writing. He was a very senior training pathologist with me at that time and I would allow a more senior trainee pathologist to use their own terminology when writing reports because it is part of their getting read to be a consultant. I would perhaps have put in some more features, but I would say that we have said there is “prominent lymphoid follicles but no histological abnormality”. By dint of saying that there are prominent lymphoid follicles, it is raising something for debate, even though we think the significance of this as a histopathological abnormality is not evident at this time. This would be the type of feature – I think it is in several other reports, where comments are being made about lymphoid follicles, even though the conclusions have been that there is no significant histological abnormality, and yet on the focused research review Drs Anthony, Dhillon and Wakefield did see this as a significant feature.

Q As you say, it does not surprise you?
A No.

Q Because of the way in which they are looking at it. You have described how the first port of call is a routine histology report as part of just the rota of reporting the child – whatever it is, Child 9 – which may be refined by you as a result of hearing what is said at the weekly meeting?
A Yes.

Q But that is still alongside another five to fifteen cases of totally different types pathology?
A And also you would see clinical details. It is not very good practice, but none were given, so we are slightly in the dark. You are not going to end up with the best report without there being a clinicopathological discussion.

Q Certainly the histology descriptions in The Lancet paper were not written by you?
A No.

Q Because you were not involved in that earlier stage, but I think you consider them to be accurate, although the terminology would not have been the same as you would use for diagnostic purposes?
A I did not then, and I still do not, use the term “non-specific chronic colitis”. That, perhaps, is the essence of my training, compared to others. In terms of the derivation of the word, you cannot really criticise the use of the word “colitis” because it means “inflammation of colon” but as I have said previously, I would tend to use the word “colitis” for active inflammation and with known patterns of disease. As we know with these children, there were no descriptions of pattern of disease that the bowel may show with autism.

Q These were the first children that were looked at, but you carried on looking at them, used for diagnostic purposes, certainly, after this. It is not just the twelve, and presumably you gained more experience?
A Very much so. We had enough to make the cohort, as I described yesterday, which I reviewed. Also, I would have got more experience. It is fair to say that with time I think I would have done more of histopathology reporting than in the earlier days in 1996.

Q Yes. You touched on that earlier – that you gained more experience. Also, presumably, you gained more experience in looking at something which was not classical IBD and was much more subtle, but it appeared to have a link to the autistic children?
A Yes. I think I would say, I began to recognise the pattern within the subsequent children coming through in a routine way. This is something I would use for teaching purposes, to feed back to other pathologists saying, “Had you seen these features”, and they said, “Yes”. I said, “This is what we think the significance of them is.” You would see later reports talking about autistic enterocolitis being generated from the department.

Q Where, again, you would have been doing the diagnostic histopathology for the purpose of treatment?
A Yes.

Q Or investigation?
A Yes.

Q I think you have seen the histology reports where they were available for the twelve children who are reported in The Lancet, including the cases where you did not write the report and you did not consider that there was any discrepancy between the comments in the original reports and as reported in The Lancet?
A I have not seen all of them.

Q Can I just ask you? Do you have a copy of your witness statement there, your first witness statement?
A No.

Q I think it is going to be produced. (Handed to the witness) I do not expect you to have your own copy there.
A I do not think I am meant to.

Q Would you turn to paragraph 65?
A Yes.

Q Is that right – that you had been shown that the histology reports were available for the twelve children reported in The Lancet paper? I appreciate you made this some time ago.
A I do not want to guess, but I think it was more in the order of four cases.

Q So those are the only ones you saw?
A It was certainly not all of them. I still have not seen all the histopathology reports of all twelve children.

Q Right. But of those that you saw, you did not consider there was any discrepancy between the comments on the diagnostic histopathology reports for them and the histological findings described in The Lancet paper? That is what you say in the statement.
A It is difficult, what you mean by “discrepancy”. Having known what was done in terms of this fine detail, yes, I can see how the terminology used is different from what is reported in the histopathology reports, but I suppose one is saying there is not discrepancy in terms of different slides were looked at, even if the terminology of the descriptions were different, and could assume to be discrepant.

Q I was only using your word “discrepancy”, that is all. What you are saying is, “I do not consider that there is a discrepancy between the comments”?
A I was asked in the context of how could it be that these sets of slides are examined for histopathology report in generating this terminology, and the same slides were looked at and generated this terminology for the paper. My answer in relation to that question was that I can perfectly well see how, in the research setting, you end up with these detailed features on the same issue.

Q So it is the point that you have already made. It is the same point, is it not?
A Yes.

MR MILLER: You can see the difference. Thank you, Dr Davies.


MR COONAN: I have no questions, thank you.

THE CHAIRMAN: Thank you. Mr Hopkins?

Cross-examined by MR HOPKINS

Q Dr Davies, I ask questions on behalf of Professor Murch. I will not detain you for very long but there are a few topics I need to go over. Forgive me if I start with some rather basic and simple propositions in relation to colonoscopy. I think you would agree that there are two principal advantages from that procedure, one that is of benefit to you, and one of benefit to the clinicians. I will just deal with the clinicians first. The clinician carrying out the colonoscopy is able to visualise the bowel tissue and identify whether or not visually there appear to be any abnormalities?
A Yes.

Q And that clinician then, in an ideal world, passes on that information to you or your department, to assist you in your role, which is to analyse and report on the biopsy samples that have been taken in that procedure?
A Yes.

Q The value in histopathology, I think it is your view, is it not, that histopathology provides a gold standard method for diagnosis of disease process in the bowel?
A I think that would be universally across all tissues in most medical practices.

Q Indeed it applies to obtaining tissues in colonoscopy from the bowel?
A Yes.

Q Your task, or the task of your colleagues, is then to interpret the findings that you see down the microscope?
A Yes.

Q So there is some degree of subjective element of that process inevitably?
A Yes.

Q I think, as you have already alluded to, the longer one spends looking down the microscope the more fine detail one may be able to see?
A Yes. With a systematic review with proforma I would expect you to find more fine detail.

Q Indeed. This whole process, particularly in the context of the case and the evidence you have given, may reveal a subtle pathology that is otherwise missed by other tests the children may undergo, would that be fair?
A Yes.

Q Over time, is it right to say that you have developed an expertise in the interpretation of subtle bowel pathology in children?
A I certainly have gained experience, yes.

Q The interpretation of that bowel pathology has to be set in the context of other clinical information that the clinicians give you, either on the histology request form or in the histology meetings that you attended?
A Yes.

Q Can we then just see, again just going back to basics, how the biopsies come to you and the information came to you or your colleagues back in ‘96 and ‘97. First of all, let us deal with the incidence of colonoscopy. That was a relatively common investigation used by the paediatric gastroenterology department at the Royal Free in ‘96/’97, was it not?
A Yes.

Q Indeed, I think something of the order of four to six colonoscopies would be performed on average each week?
A That would fit with my recollection.

Q Once a colonoscopy had been carried out and tissue samples obtained, the procedure was that the tissue samples would be put in pots of formalin and taken to your department, is that right?
A Yes, and of course they would have to be suitably labelled.

Q Indeed, they are labelled up and they would be accompanied by a request form, of the type that we have seen?
A Yes.

Q That request form, as I think you have already told us, would often be handwritten, or details on it handwritten, by a registrar assisting the consultant who is carrying out the colonoscopy?
A I cannot say who filled in the form, but some we have seen, yes, it is the registrar.

Q Can we just look at Child 4 just to illustrate this point, please, so the Royal Free notes for Child 4, and if you turn to page 33a, which is one of the yellow pages.
A Yes.

Q We have looked at this before but I do not think we have looked at this particular point. We have a proforma that is printed off, and then we see handwriting filling in details for Child 4, is that right?
A Yes.

Q Towards the left hand lower box we see “Specimen” and then written against that is identification of the specimens and the parts of the bowel that they have come from.
A Yes.

Q Below that we then see “Clinical Details”, and this is the box on the form is it not, for the clinician to tell you or your colleagues some of the key points in the clinical information that may assist in your interpretation of the slides?
A Yes.

Q For this particular child do we see that it describes complaining of “1) Diarrhoea
2) [Abdominal] pain. Has Disintegrative disorder” and then “? IBD” for inflammatory bowel disease?
A Yes.

Q So that shows the thinking, does it not, of the clinician at the time that these samples come down to your department?
A Yes.

Q Then if we just turn on two pages to page 33c we then see how that information is picked up. The clinical details, and I think you have told us these would be typed up by a secretary, is that right?
A Yes.

Q He or she has faithfully recorded the diarrhoea, the abdominal pain and the disintegrative disorder but it appears has missed off the “? IBD”.
A Yes.

Q These things obviously happen.
A Yes.

Q It then goes on to set out the specimen details, and then set out below, as you have described, the findings that were made on review microscopically, and then the comments, which I need not take you back through at all. So that was the system by which clinical information was initially imparted to you and your colleagues for the first look at the slides, and then, having carried out that exercise and reported on them, you obviously then have that histology meeting where, again, the slides can be projected up for both yourself, looking down the microscope to see, and the clinicians, who have been treating or examining the child, to give their input to you and then there is an exchange of ideas, is that right?
A Yes.

Q Thank you. That is all I need to ask by way of the system, so we can put aside Child 4. I want to move on to a separate topic, please, and for this you will need FTP3, and if you turn to page 1110. This is the start of the notes that you made, with some annotations in the margin on a couple of pages by Professor Murch, in relation to a review of slides.
A Yes.

Q You gave evidence about this yesterday. I want to go through with you some aspects of that, and, if I can put it in these terms, help jog your memory and possibly help sort out the confusion that obviously was present in your mind yesterday when you gave evidence about this.
A Yes.

Q None of what I am about to say is by way of criticism, it is meant to help. You were asked questions by Ms Smith in relation to the document we see at page 1110 in the context of The Lancet paper, and I think it would be fair to say that initially when you started telling us about the document we see at page 1110 you thought that this was part of a blinded review of slides that was in some way associated with The Lancet paper, would that be fair? That was your initial memory?
A My initial thought was that I had done this review after seeing the draft of the paper, but I think that was incorrect, although you are going to ask me---

Q I will come on to help you with the timing of the review that we see here, starting at page 1110, in a moment. Let us just separate out two things. The first thing is, before The Lancet paper was published you believe that there was some process in which you were involved considering the histology description of The Lancet twelve children, would that be fair?
A Sorry?

Q Let me start again. Before The Lancet paper was published, you believe you received a draft copy of that paper?
A I assumed so, yes.

Q Would it be fair to say that you have a memory of something happening involving you concerning the description of the pathology on the slides from children?
A I think it is only fair to say I cannot remember my thoughts on reading the draft of the paper, nor can I definitely recall any action at that time.

THE CHAIRMAN: I am sorry, Dr Davies, can you just pull the microphone a little closer to you. Thank you.

THE WITNESS: I assume I did see the draft of the paper. I am included on that list. It would be normal routine practice for any author to see it. I cannot remember my initial reaction at that time safely now some eleven years later. I believe I made no negative nor positive criticism at that time.

MR HOPKINS: Very well. Let us just deal with the dating of the paper that we see here in bundle 3. You have told us about how the slides are coded, or how the numbers that we see in the left hand column are derived.
A Yes.

Q The first two numbers relate to the year, do they not?
A Yes.

Q So, for example, on page 1110, the very first name, we see the number 97.9305.
A Yes.

Q So that means a slide in ‘97?
A Yes.

Q It was the 9,305th patient or slide?
A Case.

Q Case. Very well. Similarly, if we look to the third number down on that page, 98, that means that it dates from 1998?
A Yes.

Q Yesterday you told us that some of the 1998 numbers were so high that they must have come from the middle of 1998.
A That is my recollection, in nearly every pathology department, just as a simple numerical assessment each year for each case that is received. I cannot accurately remember the average number of cases we received at the Royal Free, I would imagine it was around 12,000-15,000 cases a year, so often one can work out the general time of year a case is from the number it is.

Q Very well. Let us just move on to page 1114, and again sticking with the left-hand column, if you go to the fourth number down, and if you need to see the original we can look at it, but that says 99.10098. Using that same system, that would mean, would it not, that that slide for that patient came from 1999?
A Or it is a typographical error.

Q Well, it is in fact a handwritten---
A Well, not typographical, a handwritten error.

Q I will come on to suggest to you why it probably is not a handwritten error in a moment. If we look at the number 10098, that again would put it fairly late in that year, would it not?
A Yes.

Q From the middle to late part of ‘99, if it is a 1999 slide. Can I suggest to you that the exercise that you were carrying out here was indeed an exercise where Professor Murch had provided you with slides for you to review in a blinded fashion?
A Yes.

Q The purpose of this exercise was not at all associated with The Lancet ‘98 paper, but was for a review of pathology in a blinded way, as you have described, for a forthcoming study and paper that was separate from The Lancet, in other words for a publication that was to come later on after 1999?
A That may well be correct as well.

Q Indeed, the reason why Professor Murch was asking you to carry out this blind review, and assisting you in it, was to ensure that there was no bias in that subsequent report that was written up. Would that fit with your recollection?
A Any blinded review should be able to minimise any bias, yes.

Q Well, I think we can then put aside the information that we have in here, and, as you rightly say, if we look at pages 1112 and 1113 we see Professor Murch’s writing on there, to the right-hand side of 1112.
A Yes.

Q I just go back to The Lancet paper itself, and, as Ms Smith reminded you yesterday, we know that that was published in February 1998.
A Yes.

Q Can I suggest to you that after a circulation of the draft version, or a draft version of that, in the latter part of 1997, around November, you, when you saw the draft, wanted to reassure yourself that the description of the histology was appropriate, and there was a meeting held, which you attended, that Dr Dhillon attended, that Dr Anthony attended, Professor Walker-Smith, Dr Wakefield, Dr Murch as he then was, Dr Thomas, Dr Casson, possibly Dr Heuschkel, and at that meeting The Lancet twelve children slides were reviewed and there was an exchange of opinions between various people present, but principally between the pathologists present, to discuss what those slides showed, to satisfy yourself and themselves that what was being written up in The Lancet about them was correct, and Professor Murch believes that that happened somewhere around November 97. Does that ring any bells with you?
A Unfortunately, not to a formalised level, no, but I certainly would not suggest that it did not happen. If they could remember the site of where it happened, it would help me.

Q It would have been in the histopathology seminar room.
A I have attended so many meetings there, it is quite feasible that I was party to such a meeting. I cannot totally recall it.

Q In which case I need not take it further, other than to suggest to you that there was a review of the draft, what was being said about the pathology on the slides, a discussion about it, and then consensus was reached about the terminology that was being used. I think, from what you have said to me, you would not disagree, but that does not actually ring any specific memory with you now, some ten or eleven years on?
A I am afraid not.

MR HOPKINS: Thank you very much.

THE CHAIRMAN: Ms Smith. Dr Davies, this is now re-examination, where Ms Smith can clarify some of the issues that have arisen from cross-examination.

Re-examined by MS SMITH

Q Dr Davies, just one brief matter arising out of the last question that Mr Hopkins at the end asked you. If there had been a meeting of the type that he has described, with a number of the co-authors of The Lancet paper at it, I appreciate you say you cannot recall it at that formalised level, but if it had taken place as he has described, and if you had attended with the concerns that you have told us that you had when you saw The Lancet paper, would you have made notes, rather as you had for the histology meetings, in relation to any discussion on a review of the slides?
A I certainly have not found any such notes in my possession, and from the description of such a meeting I think it would be quite likely for myself not to have taken notes.

Q Why do you say that?
A Because there were several written things already, and if the authors are meeting with a view to consensus, that is something that is able to be done verbally.

Q Well, can we just be clear about this. You say the authors were meeting with a view to consensus, but of course you have no recollection of this meeting at all, do you?
A At this moment in this circumstance, no, as I say, it would be twelve years on, but likewise I had forgotten about the review until asked about it in 2006.

Q You say the authors were meeting for consensus, but---
A No, sorry, that is my interpretation of a meeting that I attended, although I cannot totally recollect it now.

Q You have told us that you yourself, you personally, had concerns about the way in which the descriptions had been made.
A Yes, as I have said, the two non-specific chronic colitis is not a terminology I would use. I was happy to bow to the more senior and experienced pathologists at that time, but I think this explains in my own mind why I recalled incorrectly yesterday the timing of the review. I obviously put together the feeling of concern I had with the review that was done at a different time and incorrectly remembered them as being a cause and subsequent action.

Q When you answered Mr Hopkins’ questions in relation to the blinded view that we have the details of in the bundle, he asked you whether that might have been done in relation to a later published paper and you said it may have been for a later paper as well?
A As well as within my own mind is the way I had initially interpreted this.

Q I am sorry, I do not quite understand what you mean. What do you mean by “as well”, as well as what?
A All

Q Can I tell you what the question was again so we are clear, Dr Davies. When Mr Hopkins asked you about the blinded review we have the notes about in the bundle, he suggested to you, that that blinded review we do have the notes of was in relation to a later paper?
A Yes.

Q You said, as I heard it and tell me if there is an error in this, that it may have been, i.e. the blinded review may have been, for a later paper as well. I wondered what you meant by “as well”. In other words, what else do you think may have been covered by the blinded review?
A It is difficult to explain this. In terms of as well as my feelings of concern that I have already addressed – although I got the timing, I think, incorrect – and also, I am sorry but it is only now beginning to clink back into place which is probably why column 2 is, in particular, about the surface changes, I think that would have been another level of interest because we thought we had an established sort of pattern of change and were looking more to do with the pathogenesis, how it was coming about. I do not want to keep on conjecturing, but it is a long time ago.

Q We all understand that. Turning now to a couple of matters that you said in answer to the questions Mr Miller asked you. Going back to the time of your appointment, you will remember that Mr Miller took you to a document which was dated August 1997. If you want to remind yourself it is in volume 2 at 605aa. Do you recall this is a letter from the Director of Operations in relation to your dealings with gastroenterology and it is dated August 1997?
A Yes.

Q We know that the earliest histology meeting notes you have referred us to were in August 1996, so a year before this letter?
A Yes.

Q Was this a formalisation of what had in fact been happening, in other words, since your appointment you had in fact been acting as the designated histopathologist for the department?
A That is my understanding, yes.

Q One other matter for clarity. Mr Miller, when he was asking you about the lists that were sent to you, the lists for the discussion at the histology meeting, he said these were a list of children nominated by the gastroenterology department. I want to be clear, was it your understanding that the list that was discussed at the meeting that you had, the histopathology meeting that you had, was it your understanding that they were selected?
A No.

Q Or that every child who had tissue analysed in that department was discussed at that meeting?
A It was my understanding that we reviewed all cases. It is just that it was much easier for the paediatric gastroenterology department to identify to me the children who would have come through. As you saw, we were dealing with, sometimes, fourteen cases when my department would have had, maybe, seven hundred cases that week and so it was one of ease of identification.

Q You mean seven hundred involving every specialist in the hospital?
A Yes.

Q This may be an obvious question, in which case I apologise for it in advance. I understand what you have explained to us about the histopathology meetings; the fact that a report is generated prior to that and that you then discuss, get more clinical detail, you reach a consensus, but as far as the ultimate histopathological analysis is concerned, who does that lie with?
A The reporting consultant histopathologist would really take responsibility for a completed histopathology report, but they could take advice, opinions, from as far afield as they felt fit.

Q Going on to a slightly different topic, Mr Miller asked you these questions in the context of Child 9, but I think it applies, generally speaking, from what you have been saying. You say that one gets a better idea of the pattern of diseases when you are looking at them set against a proforma, you said you get a clearer idea of the significance of features?
A Yes.

Q Is that a situation that you would ever have from your point of view. If you were looking at the slides for clinical reasons to determine, to assist, on diagnosis and treatment for the child, would you ever be looking back at a pattern with a fixed proforma, as you do when are doing a review of the slides, or do you just look at that individual child?
A I am not quite sure I understand the question, but, in terms of general diagnostic histopathology, one has either a mental armoury or algorithm of features to look for, with frequent recourse to text books, which detail descriptions which you may want with an unusual case, set the observations you have seen down the microscope against known entities which have already been described. If you become very familiar with cases, one’s recourse to the text book becomes less frequent because you are, in your own mind, using these individual features to come to an interpretation towards a diagnosis.

Q If we could just look at the table. For Child 9, if I can remind you, Mr Miller asked you about the observations:

“Large bowel mucosa showing prominent lymphoid follicles but no histological abnormality.”

Do you recall?
A Yes.

Q You pointed out to him that there were no clinical details given in relation to that histopathology report, which is correct, and you said, obviously, that you were slightly in the dark and you were not going to get such a good report unless you had some clinical details. Is that correct?
A Yes.

Q May we look across at the meeting. We see that you said for the list for the meeting, “Nothing abnormal detected”, but we see clinical notes:

“Histology: No active inflammation. No crypt distortion.”

A Yes.

Q Would you by that stage, on the basis of what you have been telling us about these meetings, have been provided with clinical details?
A I am sure. It would be usual, as I say, for every case to be discussed with the clinical scenario from the clinicians as the child’s name was read out. It may be that, as it says, “No active inflammation. No crypt distortion”, these were features that I was asked in particular about during the meeting.

Q Are they consistent with your original description, because this is one of your reports, of no histological abnormality. Were you consistent with what you said at the meeting?
A Yes.

MS SMITH: Thank you very much, Dr Davies, I have no other questions.

THE CHAIRMAN: Thank you, Ms Smith. I am now looking at the time and it is just about 12.45 p.m. I am now going to suggest that we adjourn. The Panel members would be able to spend about 15 to 20 minutes going through their own notes to form their own lines of questioning, if they have any, of Dr Davies and also have lunch. We will now adjourn and resume at 2 o’clock.

(To the witness) Dr Davies, you are still under oath and, again, I am reminding you that you are in the middle of giving your evidence so please do not discuss this case. We will now adjourn.

(Luncheon adjournment)

Questioned by THE PANEL

DR WEBSTER: Thinking back ten years to 1997, how did your experience in histopathology compare with Doctors Dhillon, Anthony and Wakefield?
A A comparative job would have been done by myself and Dr Dhillon, who was a clinical consultant histopathologist, although he had an academic title because he was employed by the Medical School whereas I was employed by the Trust. Our responsibilities and delivery of them would have been relatively similar. In 1997 it is not my understanding that Dr Wakefield was ever a designated member of the histopathology department, but I was aware he had an office within the department for some time and I was aware of some research going on, but not direct involvement. Andrew Anthony, I believe, had worked with him and he had a physical presence within part of the histopathology department, but he was confined only to research activities at that time. He did not take part in any clinical histopathology reporting, as we have heard, with the registrars and other training pathologists.

Q Do you know if he had previously or had he been purely within research?
A It is my understanding that he had some prior experience within training in histopathology of a clinical nature.

Q From what you said, you would have had as much experience as the three other people, if not more, in some cases?
A Dr Dhillon is older than I am and would have had more years of diagnostic history of pathology. However, in terms of – I do not know his CV well enough to know his specialised exposures.

Q I was going to ask about his specialist experience, you do not know?
A I do not know his CV well enough, no.

Q If that meeting did take place in 1997 when you reviewed the twelve cases, would you have expected such a meeting to have been held?
A If there was any question of doubt, I think it would be an example of good practice to discuss things in an open forum as suggested.

Q If invited, would you have gone?
A Yes. I assume so.

Q I think you mentioned that, during the research process, they would probably be working to a proforma.
A I am only assuming that inasmuch as it would be typical of histopathologists to do detailed research review of material.

Q Is that something similar to those sheets we have seen when you went through the slides produced by Professor Murch?
A I would imagine they may even be in more detailed breakdown.

Q Would that have been presented at the meeting?
A I cannot accurately remember but I do have a vague memory now of seeing some of the sheets of paper that Andrew Anthony generated. I am trying to help but I do not want to suggest ---

Q If you cannot remember, you must say so.
A I cannot remember well enough but I would imagine that there were detailed records kept, yes.

Q It is what you would have expected?
A Yes.

DR WEBSTER: That is all I have to ask, thank you.

MS GOLDING: Yesterday, you said that you had concerns with the study in terms of the use of the word “colitis”.
A Yes, non-specific chronic colitis in particular was something that I remember. It was not the terminology I would have used in a routine way.

Q You spoke to Professor Murch and he brought you a list of names and details for blind study. Once you had carried out the study, did your concern go?
A I will have to clarify here that I think I have put two pieces of memory together in the wrong context. I have a vague recollection of some concern in terms of the pathology terminology. I know that subsequent behaviour that included me alleviated me of that fear. A strong memory I have is the blinded review that I did. I think I made an error yesterday in assuming the timeframe that I did review but, to answer your question in terms of was I convinced that there was a genuine abnormality that had been described, yes, I was supported by my observations that this was correct.

Q On this blind study that you did?
A Yes. It would appear that there were some other meetings as well where we discussed this.

Q Discussed what?
A The difference in terminology.

Q Most of the children on this blind study were autistic, that is if I am reading it correct.
A I believe that it was 21 out of 54, so they were a minority just.

Q From the results here, was there a pattern coming out to show that these autistic children had a specific identity in terms of the histopathology?
A It is my recollection that, yes, there were some repeated features. They would not be unique to these children with autism taken in isolation, but it was a repeated finding in the majority of a similar type of change seen within the tissue.

Q When we looked at all the different children that were part of the study, it appears to me that they had different patterns; the conclusions were different for each of them. How then did they have a diagnosis of chronic non-specific [colitis] and, if you go to C12, looking at the histopathology report we have for each of them, they are fairly different in terms of what the comments were.
A Yes.

Q But, for quite a few of them, we have acute or chronic non-specific colitis or reactive ileal lymphoid hyperplasia. I am assuming that most illnesses might have some kind of definitive pattern that would give you an idea of what you are looking at and, if all these children have different patterns, how would these particular 12 children come up with a similar diagnosis?
A The descriptions as used in the third column to The Lancet paper would all have been written at the same time having reviewed the 12 cases. This was the work done, according to the paper, by Drs Anthony,. Dhillon and Wakefield. So, obviously the terminology has been unified in this way, having reviewed all the others. There is obviously a larger spectrum within the first column of the histopathology report and partly this is, if you like, an idiosyncrasy of the trainee pathologist and the consultant histopathologist in how they detail their reports.

Q I do not know if this is a question for you but, in the first column, what would point to the third column? Which part of the first column ---
A If ever in the third column you see “acute cryptitis”, that should correlate somewhere with neutrophils, polymorphs, cryptitis, active inflammation. They would be synonymous. The chronic non-specific colitis would be in relation to prominent lymphoid follicles, excess chronic inflammation in the lamina propria and chronic inflammation in the lamina propria. All of those would be synonymous terms.

Q So, you agree with the description in The Lancet as well as the histopathology report. Why then was your concern so much that you went to Professor Murch about it?
A I think part of this has to be … I cannot exactly remember the time of discussions that I have had with Dr Murch and obviously it would be massively triggered in my own mind because of the aftermath of publication of the paper and, as I said before, the individual use of the word “colitis” at that time I think was open to misinterpretation as it being part of inflammatory bowel disease as we have discussed, the idiopathic ones: ulcerative colitis and Crohn’s disease.

Q Who would misinterpret it then?
A People. People reading the paper could misinterpret colitis, that we were suggesting it was inflammatory bowel disease because, in the other types of specific colitis that I know about, these are predominant in the adult population.

Q Would you look at C12 again. Does the report in column 1 go towards the care and management of the patient?
A I cannot answer this because I did not make decisions on the management. It is probably better for me to say that I cannot answer that. I know that some of the autistic children … Child 2 did in fact receive treatment and the follow-up biopsy showed improvements in the histology. I would not be able to recall accurately enough any individual discussions related to these children in terms of what management was made.

Q You said that column three would be as a result of more minute details coming out in further investigation.
A This would be the histopathological research based review that had been done, a necessary step in the preparation of The Lancet paper although I am conjecturing. I did not do the review with the three doctors; I do not know when it was done in relation to any potential decision or timing of writing the paper.

Q As an expert in your field or experienced in your field, how would you miss minute details if they were relevant to the treatment or care of a patient?
A I think that there is only one case where in The Lancet paper they say that there was acute inflammation which was not recorded in the histopathology and I am afraid that we are never 100 per cent accurate, which is why we do review cases from time and have these general discussions.

Q You have said that your name has been on several papers in paediatric trials before.
A Yes.

Q Were you told beforehand that any work you carried out would be part of the trial?
A We met frequently and there was a lot of communication between us.

Q Who is that?
A Myself and the paediatric gastroenterologists and the different registrars who were maybe the lead investigator within some different projects that were being written up would come to me at different times. I do not think that we were ever formalised into “this is what we are going to do” because it did not quite work like that. As we got closer to publication and review of cases altogether would be the normal way forward before writing a paper.

Q Is this about this particular trial or trials in general?
A In general.

Q So, you had an idea that some of the work you would do would be part of the trial but, in this case, you did not know until the draft came to you.
A Yes. I did not know these 12 children at the time we were discussing them were part in any way of a particularly different study.

MS GOLDING: Thank you.

DR MOODLEY: You said yesterday that, in children, lymphoid tissue is more prominent in the paediatric GI tract.
A Yes.

Q How much lymphoid tissue would you expect to find in normal paediatric GI tract?
A I am afraid that is an area of considerable debate and debate between paediatric and adult gastroenterologists. I will give you an example, not within the large bowel but within the stomach. A lymphoid follicle in an adult would make you think of helicobacter associated gastritis and yet most paediatric gastroenterologists or pathologists would say that it is not an infrequent finding in children without that same level as pathological significance. The grey area is when lymphoid tissue is too much and I think this is where we gain some experience in particular related to the ileal lymphonodular hyperplasia where, having seen the endoscopic images or the descriptions of what was seen down the endoscope, [we] began to appreciate that there was a certain cut-off level which I think it actually mentioned within the paper as, when you see confluence of three huge active lymphoid follicles with active germinal centres, that appeared to be the tissue correlation with what was being seen down the endoscope.

Q When you looked at the slides, did you record the presence of three or more lymphoid follicles or would you have done that?
A With time and increased experience, that would have been part of the way I would have generated the report and also the way I would have fed back to other histopathologists and taught the registrars within the department. We needed some form of standard to suggest that this is extreme rather than physiological.

Q In terms of the review for the paper done by the other people looking at the slides, you said that they were to a proforma. Do you know that?
A No, I am assuming that because that would be a standard way of histopathological review.

Q So, you never saw that proforma or had discussion about it?
A I have a vague recollection of some very detailed sheets of paper that Dr Anthony had. I do not know when I saw them.

MRS DEAN: I think that most of my questions have been covered but I do want to ask you a couple of matters. First of all, you have told us that the description of non-specific colitis is not one that you would have wanted to use particularly at the time, but could you explain to me what your view is of the difference between chronic non-specific colitis and acute non-specific colitis.
A I think that is a very important distinguishing feature. To have a increase in chronic inflammatory cells within the lamina propria is very non specific and could be related to a very large number of conditions and, in some populations different from the UK, it would almost be considered normal. However, the presence of active inflammation with neutrophils, polymorphs, whatever, causing infiltrating intercrypt epithelium causing inactive inflammation, in my mind as a pathologist is a much more significant finding to suggest pathology.

Q Thank you, that is helpful. The only other thing I wanted to ask about was the use of this term, as it were. Was it ever mentioned in the discussions that you had, the weekly meetings, when perhaps Professor Dhillon or Dr Anthony or Dr Wakefield were present. Do you recall that ever coming up?
A In these earlier cases, no, I do not think we did, but as we had seen more and more, and reviewed more, and we can recognise the features more easily, then we would have used the terminology a little bit more homogenously, shall I say.

MRS DEAN: Thank you very much.

THE CHAIRMAN: Dr Davies, I have a couple of small questions for clarification. This is just an example. If you want to have it, it is Child 3, Royal Free Hospital records.
A Yes?

Q Page 87a. I have two questions on this. First of all, the children’s list is there. Then there is a tick mark in front of some children?
A Yes.

Q What does that tick mark signify?
A It is my recollection that these would have been ticked in as much as the case was totally ready. As I said, a clerical assistant would have assisted me in printing off reports and collating the slides of the individual cases. The reason why I am saying that is that by the children without ticks, most of them have a name that I can recognise as a registrar in the department, and it would probably be that I would have realised who the case was with, who I would then need to seek out to finalise the report with them prior to the meeting.

Q And then there are some names which have been crossed?
A That I cannot help you with.

Q So we do not know what the significance of that is?
A No.

Q Right. We then have the list of circulation of this document.
A Yes.

Q Is there any list somewhere where we have the people who actually attended those meetings?
A No, I do not think we kept a formal register of attendants.

Q So we do not know who out of these people attended and who did not?
A No.

Q Was that a normal thing, that at least one person from the paediatric gastroenterology department would attend? Otherwise I would imagine that the meeting would be ---
A Oh, we would not have had a meeting.

Q Yes. Otherwise it would not carry much value.
A There was a very rare occasion of a cancellation, say, for example, if everybody was away at a paediatric gastroenterology conference. When I could not do the meeting it was deputised to somebody else, usually a senior registrar and, if possible, I would have reviewed the cases with the registrar in preparation for their involvement in the meeting.

Q Thank you; that is helpful. Can I then ask you this. In answer to Mr Hopkins earlier on this morning, I think this particular point came up, and I think you said that colonoscopy was a common investigation in children with GI symptoms. It may be that I am paraphrasing that a little bit.
A Yes. I think we can generally see there were more colonscopic-generated specimens than those from the upper GI tract.

Q Two small questions I have from that. Was that the situation in 1996/97, or does that situation still remain now? I know you are working in a different place.
A I would say it has increased into the adult population far more, where the idea of proper mapping of changes throughout the bowel, and also the increasing realisation that there may be changes down the microscope that are not necessarily visible endoscopically is an important aspect of management of all people with GI symptoms.

Q And was this the situation mainly in the Royal Free, because it is a teaching unit, it is a tertiary unit – usually these are the units which are much more pro-active for investigations? But was this only in the Royal Free, or was this a general trend to try to investigate these children more?
A No. In Barts we had multiple biopsies. At St Marks we have multiple biopsies. I cannot remember my experience well enough in Worthing Hospital, but I would say it is routine, certainly within the paediatric population, and now also in the adult population, to have in excess of seven biopsies from each case.

Q I am now going to ask you a few terms which have repeatedly appeared in different places in the pathology reports. Can you help me just to understand some of these terms – what do they actually mean. First of all, I know what you have actually said, that the lymphoid follicles are not always a significant finding. Is that correct?
A Yes. As we saw with the diagram earlier.

Q Yes, I have that here.
A Occasional lymphoid follicles is a normal component within the mucosa of the large bowel, and small bowel.

Q Are there any numbers? Does that mean that the occasional one is normal, but let us say there are a few, more than three or more than five, then suddenly it becomes significant?
A Yes. It depends a little bit on the size of the biopsy but usually they are only 2-3 mm and most people would want one lymphoid follicle as a maximum, and it not to have these very active features to it, which is the active germinal centres, tingible body macrophages. There are some recognised pathologies, like follicular proctitis, and in some other organs like follicular cholecystitis as well, where there is a very prominent lymphoid follicle reaction, and it is a recognised form of a pathological process.

Q I am going to ask you a few things. It may be that these are very basic things, but I do not work in the pathology department at all. I am a general practitioner, so you will probably understand why I am asking you these questions. Is there any difference between a follicle and a nodule? For example, a lymphoid follicle or lymphoid nodule?
A I think they are interchangeable.

Q They are interchangeable?
A Yes.

Q Okay, thank you. I think, if I understood it right, you did say that, I think, any polymorphs and neutrophils is a significant finding?
A Yes.

Q That actually signifies, obviously I would imagine, the basic understanding that it means a kind of an acute inflammation?
A Yes. Unfortunately as a pathologist I can always remember the exceptions and things that we discussed earlier – the operative effect, the traumatic effect. You may see polymorphs within the tissue. I think from my basic training and most text books, when you see neutrophils infiltrating into the crypt, that is not to be accepted as a normal feature.

Q Now the lymphocytes, does it make a difference at what level in the section of the gut that they are present? In other words, whether they are positioned in the intra-epithelial level or somewhere deeper?
A You have to be very careful in terms of focal changes within biopsies. I do not know if anybody is aware, but there would be several sections from each biopsy that would have been looked at in all these cases because if you get a lymphoid follicle within the tissue, the epithelium overlying it will be different compared to elsewhere, because there will be these intra-epithelial lymphocytes. That is a note of caution, that you do not see that as a pathological process but it is, in fact, part of the normal lympho-glandular structure. That is where the lymphocytes are trafficking back and forth through the epithelium.

Q When you say that there is an increase in intra-epithelial lymphocytes?
A Yes.

Q Increased in comparison with what?
A Normal.

Q But you only have one section. If you take a different section and then you say, “Right, okay. Three months before that was that many lymphocytes and now it is increased.”
A This is more of important within duodenal biopsies where there are tables of what is considered to be normal and abnormal. This would be predominantly in the assessment of coeliac disease which some of the children had. Again, occasionally you can have a subtle abnormality, where everything looks normal, but on higher power you then realise that there is this excess of intra-epithelial lymphocytes. That might have significance in relation to something like an allergy, like coeliac disease. The terminal ileum may show this abnormality as part of that disease process, or it can be related to some other pathologies.

Q What is the difference between increase in lymphocytes and lymphoid hyperplasia? Is it the types of the cells?
A It is really one of where you see the excess chronic inflammatory cells. The lymphoid follicle is a normal component, but there are also chronic inflammatory cells – lymphocytes, plasma cells – away from the follicle, normally present within the lamina propria. The pattern of increase is an important assessment, whether it is diffuse, whether it is patchy. So, if you like, an increase in lymphoid follicles is just one form of excess chronic inflammatory cell infiltrate, but there are some other patterns as well.

Q Thank you. And crypts, and again, repeatedly this particular term has been used - crypt architecture distortion.
A Yes.

Q If I remember it right, “crypt”, I think you said these are the elongated structures?
A Yes.

Q When the distortion takes place, what kind of a shape is it actually then?
A There are different degrees to the architectural distortion. A common one would be where, instead of it being a simple tubal structure it becomes bifid, so it looks as though it is branched. With increasing abnormality one sees almost atrophic change to the crypts where they fail to reach the full thickness of the mucosa. They can have very bizarre forms, almost going sideways, but the reason for recording of this is that it is an important component of the inflammatory bowel disease and, in particular, ulcerative colitis.

Q Do I understand it correctly, that increased distortion signifies more inflammation?
A It implies there has been previous inflammation ---

Q Which has caused the damage.
A --- which has affected the crypts and as it has regenerated, it has regenerated in a slightly abnormal form.

THE CHAIRMAN: Thank you. Thank for giving this histopathology tutorial. I have no further question, but Ms Golding has another question.

MS GOLDING: I just want to be clear on one thing. When you responded to Mrs Dean about the term “colitis”, I think you said that once you had reviewed more and saw more of the pattern ---
A Yes.

Q --- you changed your terminology. Am I right?
A I overcame my reservations of using that word.

Q I just wanted to know, when did you review more and what period of time was this you are talking about?
A I am afraid I cannot answer that directly because I am still unsure of when I did do the review which you have in the 1110.

Q You are talking about those reviews those where, once you looked through those ---
A The thing about gaining experience is that it is an ongoing process. I would have been aware of this but, if you like, that is a nice concrete record I had filed away within my papers which I could refer back to, and help me in postgraduate teaching, teaching trainees and further the idea that this low grade subtle colitis could be related to autism and deserving of discussing it with a greater number of people.

Q Can I just be clear, as well. On pages starting from 1110, which is your writing?
A Is this FTP 2?

Q It is FTP 3.
A On that first page?

Q Yes.
A Page 1110 – all that writing is mine.

Q With this one, did you know which ones were autistic or not?
A No. In the original, you see, the sixth column is in a different colour ink. That was added after I had completed the review of all 54 cases, and had written something in the “Comments” column.

MS GOLDING: Okay. Thank you very much.

THE CHAIRMAN: Thank you, Dr Davies. The Panel does not have any more questions, but counsel may come back to you with clarifications. Ms Smith?

Further re-examined by MS SMITH

Q Just a few matters, if I may, Dr Davies. Just in relation to your last observation to Ms Golding about the use of the word “colitis”, I just want to clarify what it was you said then, and what you said previously. Are you saying it is now a term that you do use yourself?
A I do use the word “colitis” in several scenarios. Since leaving the Royal Free I have not seen any more tissues taken from children. We do not have a paediatric gastroenterology department at Addenbrooke’s.

Q You explained to us this morning the context in which you yourself had previously used it when you were at the Royal Free, and you explained that that was why you had concerns about how it was used in The Lancet paper.
A Yes.

Q Now in your practice do you use it in the sense that you have always used it?
A No. Over the years there have been several other forms of low grade pathologies that have been accepted within the gastrointestinal and pathology worlds: this focal active colitis, which was not around ten/twelve years ago; lymphocytic colitis was, just about; microscopic colitis is a far more robust diagnosis, so all of these things are in a state of not flux, but increased awareness, and there has been an increase in the number of recognised entities under the umbrella “colitis”.

Q Thank you. The other matter that I wanted to ask you arising out of the chairman’s questions, and I do freely admit, Dr Davies, that I may have misunderstood, so please tell me if I am misrepresenting what was said, but it appeared to me that he asked you questions about the use of colonoscopy as an investigative procedure and your experience in previous centres in which you had been as to the frequency of that procedure, and the answer you gave related to the use of multiple biopsies, and it may be that I missed a link. Can you just recap that for me, please?
A I am sorry, I am not a clinician, I do not perform endoscopies.

Q No.
A However, it would be my understanding that most clinicians, when performing a procedure in this way, would take biopsies.

Q Yes.
A The reason why I am talking about multiple specimens is that only with the colonoscopic examination can you easily – well, not even that easily – can you get tissue from the terminal ileum, and also the multiple biopsies routinely taken from around the colon.

Q Thank you.
A Another more common investigation within adults, certainly as an initial investigation, would be the sigmoidoscopy, which is limited to the rectum and sigmoid, and obviously generating often only one sample or two samples.

Q Ms Golding asked you two questions when she first asked you questions. Again, I am sorry to go back over things, but it is the order that you were asked them in. One related to again the use of the word “colitis”, and you said it was open to misinterpretation as inflammatory bowel disease, and you said people could misinterpret it, and Ms Golding said to you, “What people?”, and I just wanted to pursue that a little with you. It was in the context of The Lancet paper, so were you talking about people who would read The Lancet article?
A Yes.

Q Would you expect those to be medical professionals, or lay people, or who?
A I am afraid I do not know who reads The Lancet. I am sure it is predominantly professionals but not exclusively.

Q Yes. The other thing she asked you was how, as an experienced histopathologist, would you miss what she described, quoting you, as the minute details which were reported in The Lancet paper if they were relevant to the treatment of the children, and you explained to us that in fact it was only in the case of one of them where there was an acute inflammation that was not reflected in the original histopathology report, and, as you said, and I am sure we all understand, occasionally that sort of instance occurs. As far as the others were concerned, did you yourself think of them, and I appreciate you are not a clinician, but did you think of them as relevant to the treatment of the children, the actual treatment, the description in The Lancet?
A Well, I think treatment also includes no treatment, and so to have chronic inflammatory cell excess would be as important to not - lack of significant features are also important in the management of patients.

Q Yes. Thank you. You were asked about, because you had mentioned it as a general research tool, the proformas that are used for the research analysis of tissue, and you told us you had a recollection of seeing a detailed sheet from Andrew Anthony. I wonder, could I ask you to look in bundle FTP7, and if you turn to divider 16 in that, please, Doctor, do you see some documents with “Report on the investigation into the possible [viral] link” at the top, and this one happens to be for Child 2? Are you in divider 16?
A Oh, I have gone too far. Yes.

Q Just go to the start of it. This is just to tell you what I am looking at. Have you got a report---
A Yes, page 235.

Q Thank you. I should say, just so the Panel understand, these are not documents that we have been through before, although we may be looking at them with the experts. They were produced by Dr Wakefield and they relate to the research findings on these children. I only want to ask you whether they are an example of the kind of proforma you are talking about. If you go to page 432 in the bundle for Child 2, is that the sort of detailed proforma in relation to the histology that you were referring to?
A This is the type of detailed analysis, yes, I would expect with a histopathology review.

Q Thank you.
A As it is tabulated and typed, I do not know if there would have been previous handwritten copies.

Q One last matter, which arose out of the questions that Dr Webster asked you originally about the respective experience of people involved in this work. Can we be clear just about the physical surroundings. You talk about the histopathology department. Did that include both doctors working on the academic side and clinical histopathologists and both?
A Yes, because the pathology department was partly within the Medical School of the Royal Free, and so an important teaching aspect of the Medical School is the museum, and several of the pathologists’ offices were physically within that part of the department. It is almost like three-quarters of a quadrangle was what the pathology department was made up of, and it was slightly irrelevant as to whether you were employed by the Medical School or the Trust as to where your actual office was.

Q Thank you. Now, just running through; Professor Dhillon, as we have been calling him, was Dr Dhillon then, is that correct?
A That is my understanding, yes.

Q He was, as you have told us, older than you and senior to you.
A Yes.

Q He was a consultant, is that correct?
A No. I am afraid I would have to check if he was a senior lecturer at that time. There is some headed notepaper from the department which will say what level he was at.

Q Can you just explain to us, remembering we do not all have a familiarity with it, Doctor, a senior lecturer in the Medical School, is that an equivalent in terms of standing with a consultant in clinical NHS practice?
A It does depend on the university, but generally in the University of London the equivalent of a consultant is a senior lecturer. To be fair, most job titles will have the honorary equivalent of each, so if he was a senior lecturer, it would be honorary consultant histopathologist.

Q Now, you have said that Dr Dhillon was a senior lecturer, i.e. he was employed on the academic side. We know that he has also done the clinical histopathology reports that you took us to coincidentally on these children.
A Yes.

Q How does that come about? Why is he clinically involved?
A At the time when I started there, the clinical responsibilities for the pathologists at the consultant level, regardless of whether – I have just remembered the exception of the Professor – basically, all of us at the same level took part in the generalised rota of reporting the general histopathology, but, likewise, all the NHS staff also took part in undergraduate teaching for the Royal Free Medical School, so on the whole our service responsibilities were very similar, although obviously someone with an academic appointment would try and spend more time with academic and research activities.

Q Now, Andrew Anthony, you have told us, as you understand it, was confined only to research. Was he a designated member of the histopathology department?
A I do not know. I do not know who would have held his contract, but he had a physical presence within the department.

Q Did he have anything to do with the clinical histopathology reporting at all?
A At the time when I was there, he did not.

Q Now, you said Dr Wakefield was never a designated member of the histopathology department, is that correct?
A That is my understanding, yes.

Q But he had an office in the department?
A When I first arrived, yes.

MS SMITH: Yes. Thank you very much, Dr Davies.


Further cross-examined by MR MILLER

Q Again, some points of clarification, if you would, and they are not going to be very long. Certainly on some of the earlier sheets for the meetings you have put the initials, or somebody has put the initials “LLB” or “SBB” as an indication of the procedure which has been undergone which has given rise to the biopsies. Again, just for information, is “LBB” a large bowel biopsy?
A Yes.

Q Which would involve a colonoscopy?
A More often than not.

Q Small bowel biopsy would be an upper – reached from the top rather than the bottom?
A Yes.

Q In terms of shorthand, we can see from the sheets what the relevant procedure was in those cases?
A Yes. I think with time that also slightly altered, where it said “colonoscopy” for some, but there was a time when the abbreviations “SBB” and “LBB” were used to say where they came from.

Q By going through the sheets, we can, if necessary, see with a pretty good – I think “OGD is sometimes used?
A Oesophago gastro duodenoscopy.

Q Yes. So that is going down to just below – we are not concerned with this in this case because we do not reach that far with the colonoscope, one hopes. (Laughter) You were asked by Mrs Dean, and I do not think it ever actually got a straight answer because you went on to explain it, but I think it is quite an important thing for us to get hold of, and it is the use of the word “acute” and “chronic”, because “acute” is sometimes used, “active” is sometimes used. “Acute” means there is ongoing inflammation, ongoing what?
A Well, it is interesting that we use words like “acute” and “active” but in fact it is related to the morphology of the inflammatory cells, so we are assuming a timeframe, and putting on this thing as “active”, but at the tissue level it means that there is an infiltrate of – in fact, neutrophils and polymorphs are also used synonymously; acute and active inflammation may be used synonymously.

Q So you make the assumption that it is acute from what you see from the cells themselves, from the morphology of the cells?
A Yes.

Q So “acute”, the assumption is that it is something as we understand acute; “chronic” may be that it has been there for some time.
A Yes.

Q Ms Golding asked you about how one can correlate, in the C12 document that you have there, which is the separate document with the three columns---
A Yes.

Q ---where would you have looked to find evidence of chronic non-specific colitis, and we will deal with that at the moment, or acute colitis. Could you just look at page 2 of that document, which relates to Child 2. If acute and chronic non-specific colitis is the conclusion that has been reached on review---
A Yes.

Q ---then you look to see if it correlates with what has been written at the time, and I think if you are looking for chronic, you might be looking for a description of chronic inflammation within the lamina propria in various parts of the colon?
A Yes. In fact, if you look at specimen I, and then III-IV-V, the pathologists have used synonymously mild chronic inflammation in the I context for the small bowel, and then later on they say there is an increase in chronic inflammatory cells within the lamina propria.

Q Yes.
A Again, these are sort of synonymous terms. Some people prefer to just list everything they see down the microscope and then make the comment afterwards, so this excess inflammatory cell infiltrate in your description then equates as your comment that we have chronic inflammation.

Q I think you explained to us earlier that in relation to a prominent lymphoid follicle, and you pointed out a lymphoid follicle on the diagram, but the germinal centre, if it is identified, suggests that there is some activity going on, is that right?
A Yes.

Q So if you find evidence of a germinal centre, again it would indicate activity perhaps?
A It is unusual enough to be worthy of comment in the description of the histopathology report.

Q If you look at the III-IV-V part, there is a reference there, just about two-thirds of the way down:

“An occasional focus of acute cryptitis is present within the ascending colon and there is mild crypt distortion.”

Then under VI “very focal cryptitis”. Do we find evidence of an acute activity, or possible acute activity, from that description?
A My interpretation of the features that you have just described, does equate with acute inflammation, yes.

Q In a rather roundabout way we get to a situation where, if you look at the whole report, and it is mirrored in the notes of the histology meeting in the middle column, there is support for the proposition that there was acute and chronic non specific colitis in this case?
A Yes.

Q Arising out of the Chairman’s point, again to identify it in its context, go to page 5 in that document. This relates to Child 5, six lines up from the bottom:

“Specimens III & IV show minor crypt architectural distortion including occasional bifid forms.”

That was what you were describing to the Chairman about the abnormal form that may follow earlier inflammation, is that right?
A Yes.

Q That is where it forks at the top?
A Or at the bottom or the side.

Q Ms Golding asked you about the concerns that you had and it is clear from your evidence that your concerns were allayed in some way. Looking at the document at page – and I am sorry to have to make you do this with two bundles – 1110, which I suspect is in bundle 3, if we look under the “Comment” column of this, do I understand the position to be that you would have completed columns 1, 2, 3, 4 and 5 and then you would be told what the diagnosis was to fill in column 6?
A Yes.

Q So that is the blinded element, that you make your findings on what you see down the microscope and you are told subsequently?
A Yes, that last column is the unblinding of the review.

Q I think in the original it is in a different coloured ink, is that right?
A Yes.

Q You can see, just flicking through, particularly on page 1111, that under the comments we have quite a few “Colitis” which you have written in there, the fourth one down, for instance, on page 1111, “? IBD”, which would be more, would perhaps be Crohn’s, I do not know. You are using the term, that is my point – whenever the timing of this is – you are using the term “colitis”?
A Yes.

Q In quite a large number of occasions, as you told us yesterday, it coincides with somebody who, it turns out, when the operation is unblinded, has been diagnosed as autistic?
A Yes.

Q If we then just turn to FTP2, page 787, this is the final conclusion of the last paragraph of the paper:

“We have identified a chronic enterocolitis ...”

Just help us about that, enterocolitis, your understanding as one of the authors, of what enterocolitis is?
A Entero will be the ilieal component and, obviously, the colitis for the colonic component.

Q It is both parts, the small bowel and large bowel?
A Yes.

“... in children that may be related to neuropsychiatric dysfunction.”

That is the end point with this particular series of cases, that you felt that this had been identified in the small number of cases at the time the paper was published?
A Yes.

Q Is it right that your position hardened, as it were, with more experience because you saw those things replicated in subsequent investigations?
A Yes. I think with constant feedback, yes, I felt it to be a robust entity.

Q One final point, Dr Davies, your reports and reviews, as you have described to the Panel, would be for the purpose of management of a particular child’s case, they would be generated for that?
A The Friday meetings?

Q Yes, and if you actually did the report itself they would be done for the purpose of helping the management of each child’s case?
A Yes.

Q Whatever that might turn out to be, and it would not be your decision as to how the case proceeded after that.
A No.

Q Or the care of the child rather than the case?
A Yes.

Q Was that the exercise in which Dr Dhillon, Dr Anthony and Dr Wakefield were involved?
A Dr Dhillon had two roles and there is one similar to me in terms of generating of reports, although it is not my recollection that he ever deputised for me for these Friday meetings. But on the other hand, with Doctors Anthony and Wakefield, I assume he would have been involved in the very detailed analysis.

Q Doing it for a different purpose rather than simply to assist in the management of the children?
A Yes.

MR MILLER: Thank you.


MR COONAN: No, thank you.


MR HOPKINS: No, thank you.

THE CHAIRMAN: Dr Davies, I thank you on behalf of the Panel for being with us most of yesterday and today to give us the benefit of your evidence. Thank you for coming and you are now released.

MS SMITH: May I ask Dr Davies not to go without the original documents which we have and we will make sure we give them back to her safely today.

(The witness withdrew)


MS SMITH: That is the last of my witnesses for today. Tomorrow morning the secretary has arranged for video equipment to be set up because we have a short video to play to you. There are one or two other bits of evidence but they do not involve live witnesses. I anticipate that it will be a short day tomorrow and you will know that that is the last day until we resume for the experts.

THE CHAIRMAN: Is 9.30 tomorrow morning the time when we will have the video equipment set up? (Agreed) We will now adjourn and resume at 9.30 tomorrow morning.

(The Panel adjourned until Thursday 6 September 2007 at 9.30 a.m.)

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