Thursday, February 2, 2012

Day 32 GMC Fitness to Practice hearing for Andrew Wakefield



Tuesday 4 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 1

THE CHAIRMAN: Good morning, everyone. I am sorry for the delayed start but we have all been doing some work. Ms Smith, I think you are going to introduce your next witness.

MS SMITH: I call Dr Susan Davies.


(Following introductions by the Chairman)

THE CHAIRMAN: I am going to ask Dr Webster to make a declaration.

DR WEBSTER: I think you know that I used to work at Addenbrooke’s. I do not think that there has ever been any contact between us.
A Not that I recall.

THE CHAIRMAN: That was just to be absolutely sure and totally transparent. Ms Smith?

Examined by MS SMITH

Q Dr Davies, would you give the Panel your full name and address, please.
A Susan Elizabeth Davies and I reside at XXX.

Q What are your medical qualifications?
A I have MB BS and now FRCPATH which is Fellow of the Royal College of Pathologists.

Q I think it is correct, as we have indeed just heard from Dr Webster, that you are now a histopathologist at Addenbrooke’s Hospital in Cambridge; is that correct?
A Yes.

Q You were at the time with which we are concerned a consultant histopathologist at the Royal Free Hospital.
A That is correct.

Q Can you tell us when you took up that post?
A It was in the autumn of 1995.

Q When did you leave it?
A In February 2002. I am sorry, I have not checked this; it was either 2001 or 2002.

Q During your time when you were employed at the Royal Free Hospital, can you tell us what your role involved.
A I was a general histopathologist but with a special interest in liver disease. I would have taken part in a rota system with all the other histopathologists in reporting all the pathology specimens coming through the department but with a special interest myself to support the liver transplant programme. Pertinent to why we are here today, I also supported the paediatric gastroenterology department and was the lead pathologist for paediatric gastrointestinal pathology for most of my time there as well.

Q Before we talk about that in a little more detail, remembering that there are lay members on the Panel but we have had some evidence in relation to this, can you tell us as a histopathologist, in general terms not worrying about any particular specialism, how does that relate to clinical medicine? First of all, do you have any actual day-to-day contact with the patients?
A No. We deal predominantly with clinicians within the hospital system rather than with general practitioners and basically any patient who has a surgical procedure that results in a specimen of tissue being obtained, whether this be a small few millimetre fragments or a large resection of the surgical specimen, this will be sent to the pathology department with an accompanying request form for histopathological analysis, the end point really to be furnishing a diagnostic opinion on the tissue that had been submitted with a view to obvious patient management.

Q That is very clear and helpful, thank you. Turning rather more to the specialism with which we are concerned, gastroenterology, firstly, when did you first meet Professor Walker-Smith?
A It would have been when I was attached as a senior registrar at St Bartholomew’s Hospital in the early 1990s.

Q What was the nature of your contact with him at that time at St Bart’s?
A It would not have been as a direct one-to-one contact but he was practising then as the paediatric gastroenterologist and I was aware of the special nature of the work in that our pathology department supported the clinical work mainly with weekly meetings and they were normally held with Professor Walker-Smith and a consultant histopathologist: Professor Slavin was important and also Dr Paul Richardson, but on occasion the more senior registrars which included myself would deputise for those meetings when someone was unavailable.

Q When you did deputise at those meetings, what exactly would you be doing at them?
A Discussing the children who had had tissue samples taken in the recent past. I remember that I also sat in on some of them with Professor Slavin to see how the meetings functioned with the specialised material.

Q We know that Professor Walker-Smith and indeed Dr Murch as he then was moved with their team from St Bartholomew’s to the Royal Free Hospital. Was that before or after you took up your post there in November 1995?
A I believe that they preceded me.

Q I have asked you about your contact with Professor Walker-Smith at St Bartholomew’s; did you also have contact with Dr Murch in the same capacity?
A Not that I recall.

Q You say that they preceded you in their arrival but was it your understanding that that was the first time there had been a designated paediatric gastroenterology unit at the Royal Free?
A Yes.

Q When you arrived, did Professor Walker-Smith ask for any specific assistance from the histology department?
A I was aware from our weekly histopathology departmental meetings that the question had been raised and been raised on more than one occasion that there was this request from paediatric gastroenterology, in particular Professor Walker-Smith, that he felt it important for there to be a nominated lead pathologist to support the service. I do remember the discussions coming up at the meetings. I have not been able to find the minutes directly related to this but because of my exposure in the past and seeing the specialised material and also with my own rotation including going to St Mark’s Hospital which specialises in gastrointestinal disease, I volunteered within our consultant body to take up that position.

Q Did you think that that request by Professor Walker-Smith for a nominated histopathologist for the paediatric gastroenterology department was an appropriate request?
A Yes. Not least, it was carrying on the full multidiscipline approach to the care of the children. I would like to add that many other disciplines in medicine have now also taken up this viewpoint of having collected (sic) the multidiscipline approach to patient management.

Q At that time, were there other specialisms who had nominated histopathologists within the department?
A Yes. As I said, I did liver pathology as well and that also had a weekly meeting at which I would have presented the salient pathology in recent cases. Other pathologists supported other clinical disciplines. It would be stretching my memory to say whether or not they also had weekly meetings. Sometimes I believe there were monthly meetings, for example with gynaecology/oncology. It would be inaccurate for me to say how many other weekly meetings there were.

Q As far as the nomination of you as designated, if you like, to the paediatric gastroenterology department, did the meetings have roughly the same sort of format as those meetings you had previously seen with Professor Walker-Smith’s department at St Bartholomew’s?
A Presumably although I sat in on very few of the meetings at St Bartholomew’s, but I would imagine that, yes, they did have the same format. They certainly had the same number of people attending or a similar number of people.

Q As far as the Royal Free was concerned, who attended these weekly histopathology meetings?
A I would be the main pathologist there. Very occasionally, a trainee histopathologist. It was my understanding that all the clinical staff who were available on the paediatric gastroenterology side would attend. Sometimes people were late coming from previous clinical sessions. There were always overseas visitors who were doing special attachments. Less frequently, research workers would also attend.

Q Just identifying that with names, as far as the clinicians attending were concerned – obviously, as you say, people have other commitments and are not always there – generally speaking, who would be attending?
A As I say, when people were available, they would be there.

Q Could you give us the names.
A Professor Walker-Smith would be there, perhaps less frequently as time went on due to other commitments elsewhere. Dr Murch would I assume be there often. Dr Thomson also. The senior registrars were different over the years that I worked there.

Q You said research staff would also attend. Who on the research staff was attending?
A Alan Phillips attended on some occasions, and Andy Wakefield attended on some occasions. With time I believe Andrew Anthony also attended some of the meetings. He was again doing the research, the histopathology.

Q And how long generally speaking did these meetings last?
A They were scheduled, I think, for about one hour around Friday lunchtimes.

Q In general terms, what did you actually discuss at those meetings? What was the format?
A I would have been furnished with the list of children’s names who had had pathology recently. I would have gone to that meeting with all the slides and the reports from each child if they were available, with a view to discussing each child in turn where I would mention the name. One of the clinical staff, usually the registrars, would give the salient clinical features, and the endoscopy findings would be also discussed. Sometimes I would be shown photographs from the endoscopy. There would then be further discussion showing some of the slides of the specimens – not all of them, because time would preclude that level of discussion. There were several hours spent before the meeting, with me preparing the cases for discussion.

Q Were the clinical records available for the child that you were discussing, do you recall?
A It is my recollection that, again, one of the registrars would turn up with a huge pile of notes, sometimes on a trolley, for all the children.

Q You have told us you would be sent a list prior to the meeting.
A Yes.

Q And that list would have the children who were to be discussed at that meeting?
A Yes.

Q Was that list sent to you?
A It was faxed to the department. I believe you have copies of these.

Q Yes. I will take you to it in a moment.
A There was a distribution list at the moment because it was actually quite time-consuming to prepare all these cases. I needed administrative help. So one of the secretarial staff or a clerical assistant would then, from the computer, generate the identifying histopathology number for each child, and we would find out if it was a completed report or where the case was in the system.

Q You have produced some examples of these lists, and particularly in relation to the meetings with which we are concerned. I am going to take you to those in a moment, Dr Davies. I just want to ask you some general questions first. Once you received that list each week, what would you do prior to the Friday meeting?
A As I say, ascertaining where in the system they were, was it a completed case or was it a case where the slides were out of the laboratory but no pathologist had finalised a report. If these were not available I would then, regardless of other commitments or whether I was on the rota, would try and speed up the reporting of those cases. Also, for example, if there had been a major resection, find out again where it was in the system and to know whether or not it would be feasible to be available for discussion on the Friday meeting. As I say, somebody else would have helped collect all the cases and the slides and the report, and I would sometimes start on the Thursday afternoon or spend a fair part of Friday morning reviewing the slides of each child with the histopathology report, using a marker pen and writing on the slide sometimes which significant pathology I wanted to show, to speed up the discussion.

Q When it came to the meeting and you presented these slides, and there was a discussion about them, did everybody join in the discussion? In broad terms, was there any sort of protocol about it, or did you all just discuss it in an informal way?
A It was not quite a free for all or all at the same time, but obviously one endoscopist would have done it, and so they might discuss the endoscopy findings. Sometimes the registrars would be furnishing the clinical information. In many ways it depended a little bit on which type of pathology the children had. Some of them would be very rare entities that generate a lot of discussion. It is also my recollection that further management decisions were made, for example further radiological investigations if, for example, they failed to get to the terminal ileum or the biopsy had failed in some way, and also some decisions on treatment were made. Also, not pertinent to these children, but when a new diagnosis of inflammatory bowel disease was made, someone would make the decision that this had to be notified to the central register.

Q Generally speaking at that meeting, Dr Davies, would you hope to have both the slides and the histopathology report that had been done?
A Yes.

Q And you told us that you had to check that that had all come through the system?
A Yes.

Q But generally speaking, is that what you had at that meeting?
A Yes.

Q The slide and the report?
A Yes. Also I used the list that was faxed to us as an aide memoire, where I would put down the main clinical question. An aide memoire, really, in terms of what I thought the general overriding comment or pathology was. You can imagine, if you have ten children all with abdominal pain and diarrhoea, you have to have something to remember which one is which.

Q Absolutely, yes. Just before I go on with the meeting, you have referred to the fact that the endoscopist would be there, and that the findings from the endoscopy would be discussed as well. I just want to make the distinction clear for the Panel, if you would. First of all, you are using the terms endoscopy when we have been talking generally about colonoscopy. Can you just explain the distinction?
A In terms of the umbrella term “endoscopy” would cover both, going down through the mouth or up through the anus, but obviously the colonoscopy would have been the generation of large bowel biopsies and also the terminal ileum.

Q At that procedure the tissue is taken ---
A Yes.

Q --- which comes to you when you do the histopathological report on.
A Yes.

Q The endoscopy report – is that the report by the person who actually does the procedure when they are looking down the telescope?
A It is my understanding they would have written in the notes in those days and sometimes, not invariably but sometimes, the person who had performed the endoscopy would describe the features that they had seen.

Q Going to the histopathology again, was it sometimes the case that the meeting – the histology meeting – reached a different histological conclusion from the one that had been put in the initial histology report?
A Yes.

Q How did it come about, first of all? You were there as the histopathologist. You produced the report which you had either written yourself or reviewed?
A Yes.

Q Then you say there might be a difference of opinion. How would that arise?
A No. I would not have reported all of the specimens.

Q Right.
A Certainly earlier on in the 1996 and 1997 because, as I said, there is a rota where general histopathologists, two at a time, were rota-ed to do the diagnostic service. So part of my preparation for the meeting would be to review other pathologists’ report on the same slide.

Q Absolutely.
A Occasionally there is a difference of interpretation. Occasionally there is a different feature that may come to light with review, but I would say generally it is one of interpretation of the same findings as to the significance of these. That is where ---

Q Sorry. Can I just stop you, simply because you say “on review”. Are you now talking about when you review what another histopathologist has reported?
A Yes.

Q Prior to the meeting?
A Yes.

Q That is one occasion where there may be a difference of opinion, you are saying?
A Yes.

Q If it arises at that stage prior to the meeting, because one of the other histopathologists has done the report, you then review it for the meeting and you feel that it is a slightly different interpretation, what do you do about that first of all?
A Because of the time scale, often I would not have time to discuss this with the other pathologists prior to the meeting. Also, I think pragmatically I would like to discuss the cases with the clinicians to see if this makes any difference in interpretation or management, etc. If we thought there was a significant difference of opinion and interpretation, I would then generate a supplementary report and I would, on every occasion if possible, discuss it with the original pathologist and we would tend to generate a report together – if they agreed with my subsequent interpretation of the same findings.

Q Would the same apply in circumstances where a clinician, for instance, raised some difference of interpretation with you in relation to a histology report that either you had done, or one of your colleagues had done?
A Yes. Yes. If they thought there was a big difference, say, from the endoscopic findings or their general clinical feelings, it would be worth reviewing again, and possibly generating, as I say, a supplementary report if it was pertinent to management of diagnostic categories.

Q Was it a usual occurrence at the meeting for a clinician to raise differences of interpretation on a histopathologist’s report?
A No.

Q And if it did occur, who would you regard in the end as being the person whose interpretation…. How did you resolve difficulties?
A I would say with consensus normally.

Q Yes.
A Although the pathologist’s interpretation is their responsibility but it would be poor practice not to take into account the full clinical scenario.

Q If you come to the conclusion that it is necessary to amend a report, you said a supplemental report is issued?
A Yes.

Q When is that done, and what happens to it?
A It should and, I assume, would have been done as soon after the meeting as possible, and the report would have been issued from the department in the normal way as the histopathology reports are sent out from the department in the internal mail – in those days.

Q I am sorry – I am not sure I heard clearly. What about the individual records of the child? Would it go into the clinical records, the revised report?
A From a histopathology department’s perspective, it is obviously computerised records which people have more access to now, but we would send out a signed hard copy from the pathology department, sometimes with copies to other places and that would be the end of our responsibility in terms of the record being within any patient notes.

Q As far as you were concerned, would it ever be the case that if a consensus was agreed at the meeting in relation to a report which had been generated which made differences to it, would you ever not issue a supplemental report?
A I think there are occasions, yes, when that would not have been furnished – a supplementary report – if we did not think it was of particular management importance.

Q When you say “of management importance”, do you mean in the treatment of the child?
A In terms of the cases we would have been discussing at these meetings, perhaps the separation of the inflammatory bowel disease patients between Crohn’s disease and ulcerative colitis, which had a different management, would have been a more significant difference to be recorded.

Q Just so that we are clear, you said you would issue a supplemental report if it made a difference to the management. Can you tell us what you mean? Management of what?
A As I said, the best examples are taken not from these children, but from other ones who were discussed at these meetings, children with bona fide inflammatory bowel disease, where the separation of Crohn’s disease and ulcerative colitis would have been important in terms of their subsequent management and treatment.

Q The treatment of the child, in other words?
A Yes.

Q I think it is the case that when you finalised your initial witness statement you had not been able to obtain the lists for the meetings during the period 1996 and 1997, but recently you have located a ring folder of lists of the type you have been telling us about which were faxed to you by the paediatric gastroenterology department for the Friday meetings for the relevant period. I am going to deal with those lists which relate to The Lancet children when we come to look at their records in a moment, but I just want to look at the earliest you have for that period, just so that we can see what the general format and what information they have is. If you would go to FTP1, please, at page 146A, which should be a report of a histology meeting for Friday 9 August 1996, which I think is the earliest you have produced. Is that correct?
A Yes.

Q If we just have a look at that, as I say, it does not have any of the children with which we are concerned on it, but the format is that there are columns of information. One of them is the names of the children down the left-hand side. Is that correct?
A Yes.

Q Then what is the printed number after that?
A That is the hospital identification number.

Q The third column, is that the specimen type?
A Correct. LBB being enlarged bowel biopsies.

Q Then we have at the bottom what you have already mentioned to us, which is the distribution list.
A Yes.

Q It starts with yours, which is ticked because if was faxed to you. Then we see Professor Walker-Smith, Dr Murch, Dr Thomson. They were all clinicians in the department. Is that correct?
A Yes.

Q Dr Alan Phillips?
A I have always thought of him as a research worker and a specialist in electromicroscopy.

Q Dr Casson, who was the registrar from whom we heard.
A Yes.

Q Dr Chai Li Ng?
A She was a registrar at that time.

Q Then Dr Smith.
A I believe she would have been a foreign research visitor.

Q Dr Wakefield. Linda Moore, Department of Histopathology?
A She is a technician within the department.

Q Then Alison Holland?
A I do not know who she is.

Q Tara Malcolm Ward. Was she an administrator or a nurse?
A Malcolm Ward was where most of the children were in-patients.

Q Sue Hicks, just to finish the list. Do you know who she is?
A I cannot remember.

Q And one to go in the file.
A Yes.

Q Was that a usual sort of distribution between clinicians and researchers?
A Sorry, what do you mean?

Q The identities of the people change through the distribution list, but you have been through them and identified them; some of them are clinicians, some are researchers. Is that a usual sort of mix for this meeting?
A For this paediatric gastroenterology meeting, yes.

Q Then we have a lot of handwriting on that sheet. Is that in fact your handwriting?
A I believe all of that is mine, yes.

Q The handwritten notes – do not worry about the actual ones on that document – when would they be made?
A The numbers, as I say, are the identifying histopathology numbers.

Q Do you mean the handwritten numbers?
A Yes. For example, the first one is 8650. In those days, I would have generated that list myself from the patient’s name and record number to be able to find it within the pathology department. Again, taking that top line, “localised active colitis” would have been my aide memoire to sort of lead the discussion when this child came up at the meeting. You can see some of them get quite complicated. Some of this would have been before the meeting and some would have been generated at the meeting. For example, in position 6, I have written “photo oesoph”, which is photograph the oesophagus, which means we have thought it was of interesting pathology and one of the clinicians would have requested a photograph for teaching or record purposes. Likewise, at the very bottom, where I have said “Return [some] slides for GOS”, I assume that is Great Ormond Street, which shows that we were already having some meetings, but this is, as I say, the first record that I have and I assume this is what I would have put down from the meeting, the little tasks I had to go and do afterwards.

Q Some of it is before the meeting to remind you of what you were going to draw everyone’s attention to at the meeting and some of it is at the meeting, because it arises out of discussions which were generated at the meeting. Is that right?
A Yes.

Q Would you ever sometimes review cases and write on these notes after the meeting?
A Not on this sheet of paper, no, but I have come across somewhere where I have said “Review” or “Do a supplementary on”. I tended to record that.

Q In this period, Dr Davies, can you help us in rough terms as to how many biopsy cases were coming into the histopathology department in the average week for routine analysis?
A It did vary, but it would appear to be between 6, 10, 12 and a major resection perhaps once a month.

Q I just want to ask you about the standard procedure when a sample is taken at colonoscopy or endoscopy and is sent by the paediatric gastroenterology department to your department, the department of histopathology. How did it arrive, first of all? How did they get from one department to the other?
A There would have been a portering system in place.

Q How did they come? In what format?
A The tissue samples would have been at the time of the procedure put into pots of formalin, because this then stops the tissue denaturing and being able to be processed to generate the slides. So every pot of formalin which contained a tissue specimen would be identified on the label as to who it came from and what the specimen was and for every case that was submitted to the histopathology department there would be an accompanying request form, which would again have the identifying name and numbers, but also the salient clinical details, sometimes with a question that the clinicians have particularly wanted to ask of the pathologist when interpreting the slides.

Q We will look at those shortly. Once it had arrived in the department, you have told us that there were a number of histopathologists who might undertake to do the report on that sample. How was it decided who was going to do the report?
A There was a rota system for the histopathologists and there were usually two consultants on and two to three trainee histopathologists. There was not a set procedure, but basically, depending upon the experience and, if you like, the general interest of the consultant histopathologist, it would be that the trainees would choose which consultant they thought more appropriate to report their cases with. As the numbers of cases became quite large – this is as a general within the department – consultants would sometimes pick up cases themselves without involving a trainee histopathologist.

Q Once a histology report had been produced, how did that come about? They looked at the slides and they produced a report, handwritten, you said.
A Yes. The trainee would, yes.

Q Then did somebody else look at the trainee’s handwritten report?
A Yes. A consultant histopathologist in certainly nearly all of these cases would have then gone through the slides with the trainee on a double-headed microscope, so both were looking at the same thing at the same time, and any amendments as thought necessary would be made to the written report, which would then go to the secretaries for typing, which would then go back to the pathologist for checking and signing off.

Q That is the report which hopefully and usually, you have told us, would be available by the time of the weekly histology meeting which then took place. Is that correct?
A Yes.

Q Were all the samples that were taken during the colonoscopy procedure sent to the clinical histopathology department?
A Pardon?

Q Of the samples which were taken during the colonoscopy, the biopsy samples, would they all go to the histopathology department and be looked at clinically in the way you have described, in other words, for clinical purposes?
A It is my understanding that, depending on the type of child who is being investigated, occasionally some adjacent biopsy samples would be treated differently. For example, being frozen down or put into different medium, because the formalin fixation can often alter some analysis that would be important for, if you like, more research-orientated investigation of the tissue.

Q If there were samples which were taken for research investigations, do you know where they went? Did they go somewhere different from your department?
A They would have been kept, for example, frozen. Tissue that had been frozen would have gone within the appropriate laboratory research facility.

Q Were you ever actually involved yourself, Dr Davies, on research analysis of tissues in the histopathology department?
A That is a different question, because some of the children had very rare diseases and there was a lot of communication between all of us back and forth, and discussing cases on the phone, say, with for example the electromicroscopist, and to say I was not involved beyond just the formalin fix is difficult to answer, so there was---

Q Sorry, to say you were not involved beyond?
A To say I am not involved formally would be correct, but there was a lot of communication and informal discussion around difficult and complex cases. Most of the published work I was involved with with this team was far more a clinicopathological one rather than, if you like, basic science at the tissue level.

Q Now, I want to turn, first of all, just to look at The Lancet paper in relation to these children because it highlights what your role was. If you go to FTP2, please, at page 783. I should make it clear, Doctor, I am going to return to this document when I have looked with you at the individual children’s records, but just at this point I wanted to ask you for your role as co-author in general terms, because it arises, I think, out of the answer that you have just given. Your name is in the co-authors, “S E Davies”, that is you, is it?
A Yes.

Q If you go on to page 784, please, under “Histology” on the left hand column – do you see where I am?
A Yes.

Q “Formalin-fixed biopsy samples of ileum and colon were assessed and reported by a pathologist (SED).”

It then says that:

“Five ileocolonic biopsy series from age-matched and site-matched controls whose reports showed histologically normal mucosa were obtained for comparison. All tissues were assessed by three other clinical and experimental pathologists”.

Then we see “APD”; is that Professor Dhillon?
A Yes.

Q “AA”, who is that?
A Andrew Anthony.

Q Who was he, as you understood it?
A He had a pathology training background but was working as a research worker without clinical role in our department.

Q “AJW”, that is Dr Wakefield?
A Yes.

Q Now, as far as your role was concerned, the assessing and reporting by you, what was that being done for?
A This would have been part of the normal workload of the department as these were diagnostic samples. It is a little disingenuous to say I reported them all, because, as you can see, my name is not on all of the reports. However, my involvement would have been at the level of the review at the clinicopathological Friday meetings.

Q Then if we go on to page 787, just to complete it, we see your name again under “Contributors”.
A Yes.

Q Dr Wakefield was a senior scientific investigator, Dr Murch and Dr Thomson did the colonoscopies, Andrew Anthony, Professor Dhillon and Dr Davies carried out the histopathology.
A Yes.

Q If we look back at 784, we see all tissues were assessed by Professor Dhillon, Andrew Anthony and Dr Wakefield. Can you explain – I mean, you may not be able to – but can you explain the difference between those two?
A Well, the three who are down as the histopathology all have recognised training in histopathology.

Q Yes.
A However, these type of samples are easily looked at by several people all at the same time, which I assume may have been the position where it says the experimental pathologists also reviewed the tissues under the methodology.

Q Okay. You can put the paper away for the moment if it gives you more room, Dr Davies, but I want to ask you how the role that you fulfilled, as is set out there, in relation to the twelve cases that are written up in that paper, how did that compare, if at all, was it different or the same as your role in assessing the biopsies from any other child that was sent to you by the Paediatric Gastroenterology Department?
A No. My role was no different, as being involved primarily reviewing all these cases on a regular basis, I think it was one of support really for the team approach to the management of these children.

Q Were you aware at the time that you did it of any particular characteristics in relation to the twelve children in The Lancet paper, at the time when those samples were taken and being discussed?
A No. They came through in a routine manner, although I am aware in some of the lists I have written the word “Andy” against them.

Q Yes. Well, we will come on to discuss why that was in a moment. Before we do that, can I ask you, first of all, did you ever see an ethics committee application in relation to a study relating to these particular children?
A Not to my recollection.

Q I mean, you said there was nothing unusual about them, but at the time you were reporting on them were you aware of their behavioural difficulties?
A Yes, because frequently the clinical details on the request form did mention autism.

Q You say not to your collection, and in fairness to you I think I ought just to ask you to look at the document that I am talking about. If you go to your FTP1 bundle, please, at page 200. You said that to your recollection you had no knowledge of an ethics committee application.
A Please can I just check what page we are looking at? Page 100 to me is blank.

Q Page 200.
A Oh! Sorry, yes.

Q This is a document which you see is to the Royal Free Ethics Committee Sub-Committee, and it had got a date on the front of it of 6 August 96.
A Yes.

Q If we go to page 233, which is the other end of it, you will see the date of submission 16 September 96.
A Yes.

Q Now, do take your time, Dr Davies, if it assists before you answer this, but do you have any recollection of seeing this application before? I mean, if it helps to look at the design and the study on page 201, and the title, that sets it out in basic terms.
A (After a pause) No.

Q You have not seen it before?
A Not to my recollection.

Q Would ethics committee applications be something that ever came your way?
A They have done, yes. Whether or not they did at the Royal Free as opposed to subsequent positions I am not sure.

Q Now, when you were reviewing the biopsies of the children who ultimately appeared in The Lancet paper, did you know whether or not they were taking part in any sort of study?
A No, I do not have a recollection of us discussing the children in this way.

Q Well, not discussing them, but were you aware that there was anything to differentiate them between the children that you were normally seeing from the Paediatric Gastroenterology Department?
A Only, I think, possibly the referral pattern, but that is conjecture more on my part.

Q As far as the referral pattern is concerned, what did you know at the time about the referral pattern, the circumstances of the referral of these particular children? You mean by that the twelve in The Lancet paper, do you?
A No. It is my understanding that over and above those twelve children, we were involved in the investigation of many children with autism, and in no way did I feel that those twelve were singled out in any way.

Q Now, as far as the referral pattern of the children with autism whose samples you were asked to review is concerned, what was it that you understood about the referral pattern?
A I would say a child’s name, the clinician would start with the important clinical information, and I have a recollection of one or two, I cannot say for certain whether it was any of these twelve children, that say these people made themselves known to Dr Wakefield and then subsequently they came through the general investigation.

Q Sorry, you say that was said at the time, not on paper; you are saying you have a recollection of the clinician saying that?
A I have a recollection of one or two cases in this way, of children with autism. I have a recollection of an occasional child being mentioned in this way as we began to discuss them.

Q Sorry, Dr Davies, mentioned in which way?
A Oh, that they had made themselves known to Dr Wakefield.

Q Now, you have mentioned children generally, but I want to ask you about something which you have referred to already, which is the particular children in The Lancet paper, and the reference to “Andy” beside their names. If we go to Child 2, his Royal Free Hospital records, please, and at the same time if you could get Child 8’s Royal Free Hospital records. So Child 2 and Child 8. You can put Child 8’s records to one side for a moment and just look at Child 2 at page 265A. Dr Davies, from now on, we are likely to be referring to records with names in and you have in front of you a laminated plastic sheet which has the names with numbers to anonymise them to protect confidentiality. Would you try and use it but the press have been warned that we all make mistakes and, if you do mention a name, it is not the end of the world. Would you look at page 265A and does the name at the top of that page correspond with the number 2 on the sheet in front of you?
A Yes.

Q If we look to the left, is that what you are referring to, the “Andy” that you have written beside that?
A Yes.

Q Is that your handwriting?
A Yes.

Q I am going to ask you to look at Child 8 now and then I will ask you the question in relation to both. Would you look at Child 8 at page 61A, please. Again, if you look at the fifth child’s name down on that list, is that Child 8 on the sheet you have in front of you?
A Yes.

Q Again, have you written “Andy” this time next to the hospital number?
A Yes.

Q Is that your handwriting again?
A Yes.

Q First of all, do you have any recollection as to why you would have written that in respect of both these children?
A No.

Q To whom are you referring there?
A I assume it to be Andy Wakefield because, if I refer you back to Child 2, you see that there are several other names in the left-hand column, Alberto, Tara and Jill, and I recognise these as trainee histopathologists within the department. I assume that is where the cases were when I was trying to generate the meeting. I do not recall a trainee by the name of Andy.

Q You assume that it is Andy Wakefield. Why would you have been putting Dr Wakefield’s name by those children’s names, if it is his name?
A I am unsure. It may have been because there was something about the clinical details that made me suspect … I am sure because … These are from earlier meetings where I do not seem to have put down the clinical details for every case whereas, as time went on, I did. Whether or not it said “autism”, I have no recollection.

Q Why do you think you would have been writing Dr Wakefield’s name in relation to something to do with the clinical details of the child?
A I cannot recall.

MS SMITH: I understand that you do not recall, Dr Davies, but I asked you what reason there could be and you said that it was something to do with the clinical details although ---

MR COONAN: I am sorry to interrupt but this is verging on the cross-examination in the light of that last answer. I say “verging”.

MS SMITH: Until I have verged, perhaps I can go on asking the questions. When I verge, Mr Coonan will get up and stop me no doubt.

MR COONAN: I have made the point.

MS SMITH: Yes, you have and I have taken it on board and, as I say, I shall continue to verge.

THE CHAIRMAN: I have just been advised that it would probably be better for the question to be rephrased, Ms Smith.

MS SMITH: (To the witness) Let us start again on it, Dr Davies. You raised particularly, when you were answering your questions, the fact that you had written by children’s names “Andy” and you have told us that you think you were referring to Dr Wakefield.
A Yes.

Q I asked you whether you could recall why and you said that you could not. I asked you whether you could assist us as to why you might have done and you then said that it might have been something to do with the clinical details of the children.
A Yes.

Q I would like you to explain to the Panel what that means, please.
A I do not think I can help because, on the same page of Child 8 towards the bottom, there is another child who I have written the clinical details “autism” against. So, it is certainly not that whenever I saw a child [with] the clinical details of autism I wrote “Andy”. I do not know. I do not know what information I was using to put that name against some of these children.

Q You have referred in particular to Child 2. Does the same apply in relation to Child 8? I have asked you the questions in relation to Child 2.
A Yes. Where I have put “Andy” against a child’s name, I cannot recall what information I was in receipt of or what assumptions I made in terms of jotting that down.

Q You have mentioned the circumstances of referral as being something that you were aware of at the time in relation to children with autism. Can you help us as to what in particular was your understanding of the circumstances of referral in relation to the children with autism.
A I do not think that there was any set pattern and it is not my recollection that they could all be grouped together in any way. I was aware that some of the children who we were investigating had come to the attention of Dr Wakefield in some way.

Q When you say that you were aware that they had come to his attention, in what respect?
A Sometimes with the clinical details or when we were discussing the case, Dr Wakefield’s name would be mentioned but I would also like to add that, on several other occasions, another clinician would also be mentioned, sort of “This child has come from Dr X from St Elsewhere’s” where they were known to the team. It was not an exclusive term.

Q Were you aware of any other investigations which were being carried out on the children with autism?
A Not directly at the time although, as I say, the clinical information was tending to be restricted towards the analysis of the gastrointestinal tissue, so time was of an essence in relation to the discussion of these cases.

Q I should perhaps have asked you before in order that we are all clear. Did you play any part in the decision as to whether these children underwent endoscopies or colonoscopies which provided the tissue which you analysed?
A No, as I would not with any of the children who were investigated in this way.

Q You have told us that you were not aware at the time of any sort of study relating to these children in particular. Was there a point when you did become aware that these children with autism were part of the study?
A Yes, a general awareness of investigation of these children, but a lot of the children were being investigated and were taking part in clinical trials as well which were not always discussed at our meetings.

Q When did you become aware that children with autism were part of some sort of study?
A I cannot give you a definite date although obviously I was definitely aware at the time of seeing a draft paper which was subsequently submitted to The Lancet.

Q Absolutely because you were a co-author on it.
A Yes.

Q Were you aware of it before you saw the draft? Were you just sent the draft of that paper?
A It is quite feasible that someone mentioned, “These children should be written up” but I cannot say when, where or who.

MS SMITH: I want to turn now to look at the individual children’s records, in particular the part which your role was involved in, in other words the histopathology reports and the notes relating to the histopathology meetings. and I am going to deal with these children in the chronological order in which they were referred to the Royal Free. Would you go back to the Royal Free Hospital records for Child 2 first of all.

THE CHAIRMAN: Ms Smith, I know that we started late but I do know that the witness was here for some time before that and it may be that we should give her a short break before you embark on the individual records.

MS SMITH: Sir, this is a good moment.

THE CHAIRMAN: We will have a short break of 15 minutes. (To the witness) Dr Davies, you are under oath and are in the middle of giving your evidence. Please, make sure that you do not discuss this case with anyone during this period. I am sure that someone will look after you with a drink. We will now adjourn and resume at 12.25.

(The Panel adjourned for a short while)

MS SMITH: (To the witness) Dr Davies, I want to turn now to look at the individual records and begin with Child 2. We have already identified the name on your chart. This is a case where your name does not appear on the typed histology report but you have recently found the notes for the relevant histology meeting and, to put those in context, I want to go to the histopathology report first which is at page 264. That is the printed report. If we turn back to page 263A, is that the initial request for the histopathology?
A Yes.

Q That gives the specimens and the clinical details.
A Yes.

Q If you would go on to page 263B, would that be the original handwritten comments by the trainee that you have described to us?
A There are two. Most of that script I recognise as AQ which is the trainee pathologist Quaglia, and the little bit at the bottom, the last three lines, I recognise the writing of JC, the consultant.

Q You may be asked some more questions about those documents but I want to take you to the printed report which is on page 264. We see at the top left, “Date of Receipt 02/09/96” and does that mean the date that the samples were received?
A When I received them in the laboratory, yes.

Q If we look at the bottom of the page, page 264, we get the print date.
A Yes.

Q That is presumably the date when this report was printed up.
A Yes.

Q We see,

“Clinical Details

Autistic/hyperactivity. Diarrhoea intermittent for many years. 3 [episodes of] obstructive jaundice” and “? Crohn’s disease.”

Is that a replication of the clinical details you were given when the sample was sent?
A Yes. That is transcribed by a secretary in the histopathology department taken from the handwritten request form.

Q Where would that information have been derived from?
A That would have been filled in by the submitting clinician. In this case, it is the doctor’s name on the top right where it says “Consultant JAWS” which is obviously Walker-Smith. That would presumably be a registrar filling in the details at the time of endoscopy with their contact bleep number.

Q May we go through this. On the left-hand side we have the name and then we have, “Ward: MALC” and that is Malcolm Ward, is it not?
A Yes.

Q What was your understanding of the specialism within that ward? Was it entirely paediatric gastroenterology?
A That I cannot answer. I do not know if there were other paediatric cases there but certainly most of our specimens would have come from paediatric gastroenterology.

Q We see “Consultant” and we see “Professor Walker-Smith”. What does that denote?
A He would have taken overall charge of this case. The child would have been admitted under his name.

Q Then, if we go to page 264, we see the specimen details, in other words where the specimens were taken from. Is that correct?
A Yes.

Q And the microscopic description of them?
A Yes.

Q That is the naked eye description. Is that correct?
A Yes.

Q If we go over, we see the microscopic description, and this is when the reporter is looking down the microscope at those samples?
A That is correct.

Q If we just run through that:

“There are fragments of small bowel mucosa with mild chronic inflammation within the lamina propria. No granulomas are identified.”

These are the comments under each of the samples, which is taken from the page before.
A Yes.

Q So that is the comment in relation to the terminal ileum at I. Then the second one is the caecum, et cetera. The second one is:

“These are fragments of large bowel mucosa with a moderate chronic inflammatory infiltrate within the lamina propria. No granulomas are identified.”

Then samples III, and IV-V:

“III-IV-V All these specimens show fragments of large bowel mucosa with patchy increase of chronic inflammatory cells within the lamina propria and occasional prominent lymphoid follicle with a germinal centre within the ascending and transverse colon biopsies. An occasional focus of acute cryptitis is present within the ascending colon specimen and there is mild crypt distortion. No granulomas are identified.

VI This is a fragment of large bowel mucosa with mild chronic inflammation of the lamina propria and very focal cryptitis.”

Then there is a comment section, which says:

“COMMENT 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.”

Can I ask you, Dr Davies, is that a standard way in which histopathology is reported? In other words, with detailed comments about each specimen, and then a general comment summarising the situation at the end?
A As an overall way of laying out reports, yes, I would agree.

Q We see that it is Dr Quaglia and Dr Crow. Who were they?
A Dr Quaglia would have been the trainee histopathologist involved with this case, and Dr Crow would be the supervising consultant pathologist who would be taking overall responsibility for the generation of this report.

Q What does the little “(P)” by Dr Crow’s name mean?
A This is, I think, unique to the Royal Free histopathology department, when “(P)” means “participated”, which means there was direct involvement. On some other cases – I do not believe with any of the children in question – the letter “(S)” may have been written, and this would have been “supervised by”, which actually meant that the consultant had no direct input into the case but had taken a decision that this trainee was of sufficient experience that they could do those cases on their own.

Q Then “Initials of issuing pathologist” at the bottom?
A That is “AQ”.

Q I notice, so I will ask you on this one, Dr Davies, so I do not have to ask you again – all these histopathology reports have “Whole report invalid if any page unsigned or missing”.
A Yes.

Q Is that an important aspect of your particular specialism?
A Yes.

Q That there are safeguards?
A Yes.

Q Why?
A Because a report might have been generated by a secretary. In fact there are typographical errors in this report anyway, but there may be errors, mis-spelling, etc., and it would be the pathologist’s responsibility to proof these reports and, if necessary, another one would have to be printed off again, and it was only the finalised report which would then be authorised. Many departments do not do this manually any more, with the signatures, but the pathologist verifies every part of the report on the computer screen themselves.

Q And how important within your specialism is complete accuracy?
A Within the limits of human involvement, I would say pathologists take very seriously the aspect of fine attention to detail.

Q We know, because we have already been through it, this is a case where we have the list for the combined meeting. If you go on to page 265a, there it is. You have told us already that it is your handwriting on this list. If you were taking the meeting, would you have reviewed the histology report that we have just looked at?
A Yes – and the slides, yes.

Q We have dealt with the “Andy” that you have written on the left hand side, and now I want to ask you this. The only other thing that is written by you on there is the number on the right. Is that correct?
A For this individual child, yes.

Q That is the histopathology number – is that right?
A Yes.

Q 9731-96. If we look back at page 264 ---?
A Yes.

Q We can see that number. Does that identify that the samples are ---
A Sorry – yes.

Q That meeting in fact is also recorded in the clinical notes in relation to this child. Could you go to page 14, please. This is the note of the histology meeting, and we have heard from Dr Casson, Professor Walker-Smith’s registrar, that these are his notes. Would that be a normal process for the notes of the meeting to be recorded in the child’s clinical records?
A The notes, it is my recollection, were always available, as opposed to who transcribed what in the clinical records themselves I would not be able to comment on because I was busy and physically separated from the clinicians during the time.

Q I am sorry? You mean, if it was written up after the meeting you were physically separated?
A No, no, no. I was not sitting with the registrars, with their notes, which they might have been writing in. I would have been facing them, and there would have been a microscope between us.

Q Yes, absolutely. Just for the sake of completeness, I am going to read that note out, just to remind the Panel, Dr Davies, because this is evidence that Dr Casson has already given – what this note in fact says. It says:

“Histology meeting

Terminal ileum – no obvious inflam [inflammation]
Entire colonic series - [Increase in] Chronic inflammatory cells in mucosa
Some oedema
One section odd ? [possibly] epithelial cell
Marked lymphoid hyperplasia [with] some evidence of neutrophil infiltration of crypt
Unusual to see such lymphoid changes in transverse colon
Rectum sl [slightly] degenerate epithelium [with a] collection of polymorphs.”

That is all the histopathology information in relation to the colonoscopy which was carried out on Child 2 originally. We know, in fact, that a second colonoscopy was carried out because this little boy was put on to enteral feeding and there is a second histology report which is at page 268. The date of this report on the left hand side, 11 November 1996 and the print date of 14 November 1996. Is that correct?
A Yes.

Q The last page of it is on page 270 in fact, because of the oddities of the record. We see the microscopic description starting on page 268:

“I. Sections show superficial small intestinal type mucosa, with well-formed and normal villi. There is no increase in inflammatory cells.

II-VII Sections from all the colonic biopsies show large bowel mucosa, within normal histological limits. There is no excess inflammatory cell infiltrate, and granulomas are not seen. Occasional small lymphoid aggregates are seen in the biopsy series, but these do not appear abnormal.

Comment: Within normal histological limits.”

And who is the reporter on that?
A Dr Jarmulowicz, who is another consultant histopathologist in the department. Where it says, “Comment: Within normal histological limits” it says “MJ”. That is him, is it?
A Yes.

Q And then “SD”?
A Unfortunately “SD” are the initials of the secretary who typed that part of the report. I think I am nearly always referred to as “SED” in this department.

Q So there was no one else involved with that, because that done by another consultant. Is that correct?
A Yes.

Q We have your notes for the histology meeting relating to those slides at page 270a. Is Child 2 the fifth name down on that list?
A Yes.

Q And whose handwriting is it beside his name?
A Mine.

Q Thank you. Again, is that number 12601 9731 the histology number?
A Yes. The two reports you have just discussed.

Q If we look back at 268, we can see the number again at the top of the page? Is that correct?
A Yes.

Q Then the only other handwriting – is that also yours?
A Yes.

Q Can you translate for us what that says, please?
A “NAD” which is my shorthand for “No abnormality detected”.

Q Yes?
A And that is in the position of 12601, but 9731 I have put “Mild prev [previously]”. That is “prev” I have written.

Q What does “mild previously” mean? Mild what?
A Interpreting it in the light of the histology report of 9731, that there was mild active chronic inflammation.

Q So it is mild, active chronic inflammation previously, i.e. related to the first report. Nothing abnormal detected relating to the second. Is that correct?
A Yes.

Q There is one other document which I just want to take you to. They are some histology notes which are written on the colonoscopy report, not the histopathology report, which you may or may not be able to help with. They are on page 248, please. I am not asking you to speculate about these, Dr Davies. I just want to know whether you can help at all. First of all, it is not your handwriting, is it?
A No.

Q Is it usual at all to have histology notes like this, handwritten on an endoscopy report?
A No. It would be very rare occasions where I would ever have resource to look at patient records in this way. But can we please check the date of the meeting?

Q Yes. If you go back, it is the same date, in fact – but you can go back if you wish to. It is page 270a, 15 November.
A No. That is the follow-up meeting. Is there one --- Sorry. I beg your pardon.

Q 15 November.
A My assumption would be that this was written at the time of the histology meeting.

Q Could you put those away, please, and take out the records for Child 1. Dr Davies, you may not be able to answer this now – as I say, do not tell us if you are guessing – but do you happen to know whose handwriting that was?
A No.

Q Would you just look at the anonymisation sheet so that you know the name of the child.
A Yes.

Q And then go, please, to page 101. This first histopathology report in relation to this child is from an upper GI endoscopy. Is that correct?
A Yes.

Q Just explain that again, remembering we have lay members, would you? Explain the difference between that and colonoscopy for the Panel.
A An endoscopy includes both the upper gastrointestinal tract and it is called an upper GI endoscopy, but when the large bowel is examined by the same endoscopic procedure, it is called a colonoscopy. So this child had both an upper GI endoscopy and a colonoscopy.

Q I am going to deal with the upper endoscopy very briefly. There is a report printed on 30 July 1996 and in fact if we just go to the comments it says “Mild gastric changes”. It has Dr Rees and your own name.
A Yes.

Q With the “P” beside it which you have explained. Who was Dr Rees?
A She was a trainee histopathologist in the department at that time.

Q If you then go on to page 103, we get the report from the samples taken from the colonoscopy. The date of the samples is 26 July 1996 and the report was printed on 30 July 1996. If we go to the microscopic description, we see:

“Sections show large bowel mucosa with a somewhat distorted lymphoglandular lesion with no histological abnormality.”

Then the second sample:

“Large bowel mucosa with preserved architecture. There is a patchy chronic inflammatory infiltrate. There is a focus of transepithelial neutrophil migration (cryptitis) with incipient crypt abscess formation. No granulomas, ova or parasites are seen.”

Then sections III and IV:

“Sections show pieces of large bowel mucosa within normal histological limits.

Comment: Colonic serial biopsies with focal active chronic inflammation in caecum [in the second sample].”

That is again Dr Rees, the trainee, and you. Is that correct?
A Yes.

Q There is a handwritten note at the bottom of the page, page 104. Is that “seen by”?
A It may just be “seen” and someone’s initial.

Q Can you help us, because this appears on a number of these reports, as to why that would be on there?
A It would only be conjecture, that this was a clinician who, when seeing the histopathology report, was acknowledging that it had been read, because it is the day after it was issued from our department.

Q Then if you could turn on, please, to Child 3, the Royal Free records. This is a case where your name does not appear on the typed histology report, but one where you have recently found a list for the relevant histology meeting. Just to put that list in context, can we see what was said on the original report at page 86? We see again at the top that the ward is Malcolm Ward, the consultant is Professor Walker-Smith, the date of receipt was 10 September 1996 and the print date at the bottom of the page is 13 September 1996. The microscopic description of the first description is:

“Shows small bowel mucosa with an increase in intra-epithelial small lymphocytes, but no architectural abnormality.”

The second sample:

“Shows small bowel mucosa with prominent lymphoid follicles.”

Then the third to the seventh samples:

“Each show large bowel type mucosa within normal histological limits.

Comment: mild inflammatory and reactive changes in the small bowel samples, of uncertain significance on morphological grounds alone. No microbes or granulomas identified in any of these samples.”

Can you tell us what “morphological” means, Dr Davies?
A It is the description of the tissues themselves. So it is the form that they have.

Q This is a report which was done by Professor or, as he then was, Dr Dhillon. Is that correct?
A Yes.

Q If we go on, please, to the list for the subsequent histology meeting, which is one we have seen already in the context of Child 2, we have another copy at page 87A and we have looked at it in relation to the child’s name at the top of the page, Child 2, but if you look down to the tenth child down, is that Child 3?
A Yes.

Q Again, are the notes written by you?
A Yes, although these are nearly all just numbers.

Q Indeed, as far as Child 3 is concerned, we just have the number. If we look back at page 86, we will see that that number coincides with the number on the samples. Is that correct?
A Yes.

Q There are no other notes, as you rightly say, Dr Davies. In general terms, what does that denote? If there is a histology report with comments as we have seen in its full typed final form and there is no comment on the histology meeting, what conclusion can be drawn from that, if any?
A Unfortunately, there are two possible interpretations here, because I do note that on the same sheet there is a child under position 6 where I have written “called normal – but patchy enteropathy”, which is obviously a note to myself about a totally different child. By implication, it may be that I was in agreement with the original histopathology report or it may have been that no discussion was generated in particular at the meeting, but I think on reflection this was a list from relatively early on in our meetings and I had not realised or had not got into the habit of making a little aide memoire on it.

Q If anything significant had been changed at that meeting, what would have been the implications of that so far as the histopathology report was concerned?
A If it was at a significant level, I would have discussed it with the clinicians, discussed it with Dr Dhillon, to see if we needed to do a supplemental report. By implication, on the same page there is this other child where there may have been further action taken, but this is not relevant to our children.

Q Can we turn on to Child 4, please, and go to page 33C? This is a report for this child. The specimen was received on 30 September 1996 and the report issued on 2 October 1996. This is a document which you found recently. Is that correct?
A No.

Q If we look at the microscopic description, we see:

“I. Small bowel type mucosa with a lymphoid follicle.

II-VII. Large bowel mucosa, some with attached muscularis mucosae with no evidence of architectural distortion or increase in inflammatory cells in the lamina propria. Lymphoid follicles with germinal centres are present in many of the biopsies. No cryptitis or crypt abscesses are seen. The surface epithelium appears intact. No granulomas, ova or parasites are seen.

Comment: Large bowel series with terminal ileum, with no histopathological abnormality.”

That is a report generated by the trainee, Dr Rees, and by you participating. Is that correct?
A Yes.

Q In fact, this child is not referred to in any of the lists for histology meetings which you have found, but we do have a clinical record in relation to the histology meeting and that is at page 13. Again, it is a note by Dr Casson and I will just read it into the transcript, if I may. It says:

“4 October 1996. Histology meeting

• Dense lymphoid pattern
• No acute inflammation
• Normal architecture

• Prominent lymphoid follicles
• No active inflammation

No granulomas”

If we can turn on to Child 6, please, Dr Davies. This is in the additional Royal Free records. This is another child where you were not involved in the creation of the initial report, but you found the list for the relevant histology meeting. If we can just look at the histopathology report, please, which is at page 150, we see again the admission was to Malcolm Ward and the consultant was Professor Walker-Smith. The date of receipt of the samples was 28 October 1996 and the print date is 1 November 1996. The clinical details are given as:

“Recurrent abdominal pain. Loose stool, no blood, no mucus. Symptoms possibly related to measles vaccination → also autistic tendency”

Then under “Microscopic description”:

“I. Sections showed pieces of small intestinal type mucosa with normal villous architecture and a piece of probable ileocaecal mucosa with prominent reactive lymphoid follicles and a mild focal cryptitis. No granulomas or parasites are seen.

II-V. Sections show large bowel mucosa, some with attached muscularis mucosae, with prominent lymphoid follicles. There is a mild patchy increase in inflammatory cells interest he lamina propria with focal cryptitis but no crypt abscess formation. There is mild architectural distortion with focal irregularity of the surface epithelium. No granulomas or pathogens are identified.

Comment: Colonic series with a mild histologically non-specific proctocolitis.”

That is from Dr Rees, the trainee, with Dr Dhillon, the consultant, participating. Is that correct?
A Yes.

Q You found the list for the histology meeting and that is at page 151A. Is Child 6 the first child on that list for Friday 1 November 1996?
A Yes.

Q Again, is that your handwriting?
A Yes.

Q Can you tell us what you have said in relation to that child?
A My interpretation of my own notes there would be “Slight active patchy ileum/rectum”, which would appear to be an aide memoire of what to show from the slides and the histopathology report. The Delta sign means a diagnosis of microscopic, which is written to the left of that. That may have been written at the time of the meeting, as I have not recorded on this occasion any other clinical information.

Q In fact, we do have a detailed note of that histology meeting at page 46 in the clinical records. Again, Dr Casson has kindly translated his handwriting on this note for us. It says:

“Terminal ileum – three lymph follicles in biopsy
Slight increase in chronic inflammatory cells within the laminum propria
Few cells infiltrate surface epithelium in a patchy manner
Occasional polymorph in crypt

Colonic series – similar throughout
Normal crypt architecture
Minor goblet cell depletion with patchy polymorph infiltration of epithelium

Microscopic colitis which is not lymphocytic and is in a patchy active distribution throughout the colon.”

A No, that is “pancolitis” I would have said, “patchy active pancolitis”.

Q Well, as I say, I have taken this from the transcript which Dr Casson gave us of what his handwriting is, but you may or may not be correct. Anyway, we will check it, Dr Davies, but thank you very much. Then can we go on to Child 9, please, and again if we just identify him on your sheet and then turn to page 48. We see again Malcolm Ward, consultant Professor Walker-Smith, date of receipt of the samples 18 November 96, and then a print date of 22 November 96. This is a report in which you were directly involved. The clinical details, “None given”, and then a microscopic description:

“Specimen I. Small bowel mucosa showing no histological abnormality.

Specimen II-VII. Large bowel mucosa showing prominent lymphoid follicles but no histological abnormality.”

Is that correct?
A Yes.

Q That is you participating and who is Dr Maddox?
A He would have been again a senior trainee pathologist.

Q You have also found the list that relates to the histology meeting in relation to this child and it is at 48a. Is Child 9 Child 8 on that list, with a misspelling of his surname?
A Yes.

Q We know that by the sample numbers and by the date of the meeting, is that correct, that it is the same child?
A Yes. His hospital identification number is correct.

Q Yes. There is a note by his name. Is that your handwriting?
A Yes.

Q We see the histopathology number, and then can you tell us what it says after that?
A Again that is “NAD”.

Q Which stands for?
A “No abnormality detected”.

Q If we also look in the records, please, at page 8 in the clinical records, there is a note there which has been made in relation to the histology, although whether it is actually a histology meeting or not, or as a result of it, is not clear. It simply says: “No active information. No crypt distortion.” Have you found that?
A Yes.

Q Can I now ask you to go to Child 5. (To the chairman) Sir, I am not sure what time you wanted to continue to, that is why I was hesitating.

THE CHAIRMAN: Five or ten minutes if you want to.

MS SMITH: Well, it depends when you would like to break, how many children do you want to fit in? I am very happy to do another one, sir.

THE CHAIRMAN: I think we might as well adjourn now.

MS SMITH: Yes sir. I would be rushing a bit, I think, to get through another one.

THE CHAIRMAN: No, we do not want that. So it is now quarter-past one and we will now adjourn and resume at quarter-past two. Dr Davies, I remind you that you are still under oath and in the middle of giving evidence, so please do not discuss this case with anyone, including any lawyers. I am sure someone will look after you for lunch.

(Luncheon adjournment)


MS SMITH: I am going to turn on now to Child 5, if you could look up the Royal Free records for Child 5, Dr Davies, page 429, please. Have you found the report? Are you with me?
A Yes.

Q The date of receipt of the samples was 2 December 96 and the date the report was printed is 4 December 96. We see again Malcolm Ward, consultant Professor Walker-Smith.

“Clinical Details

Child with autism and diarrhoea and [abdominal] pain.
Possible inflammatory bowel disease. Endoscopy – Mild rectal inflammation. Some mild lymph nodes on” –

is that “terminal ileum”?
A Yes.

Q Then the microscopic description is on page 430:

“Specimen I consists of fragments of small intestinal mucosa which includes lymphoid follicles but which is without pathological abnormality.

Specimens II, III & IV are large bowel mucosa fragments with normal crypt architecture. There is at best a minimal increase in chronic inflammatory cells within the superficial lamina propria. No active inflammation is seen. Specimens III & IV show minor crypt architectural distortion including occasional bifid forms. Paneth cell metaplasia is not seen. No excess chronic inflammatory cells are seen. A very occasional polymorph is seen within surface crypt epithelium. No ova granulomas or parasites are seen in any of these biopsies.”

The comment then is:

“Large bowel series; minor changes the significance of which are uncertain but do not amount to the diagnosis of inflammatory bowel disease.”

We then have “SED/JC”; that is your initials and your secretary, is that correct?
A Yes.

Q Included on the bottom of the report in manuscript:

“N.B. Report when seen by [Professor Walker-Smith] – seemed to be more significant inflammation than indicated in this report”.

As far as those handwritten comments are concerned, Dr Davies, are they in your handwriting?
A No, but the initials “SED” at the bottom are mine.

Q Yes. Thank you. When would you have put those initials on? It says “Initials of issuing pathologist”.
A Yes. That would have been when it was authorised on that print date of 4 December.

Q Can you help at all as to whose handwriting that is?
A No.

Q If we go on, I think this is a case where you have found a report of the weekly histology meeting, and we can see that if we go on to 430a, the next page.
A Yes.

Q Child 5 is Child 1 at the top of that page, is that correct?
A Yes.

Q Is it your handwriting on this?
A Yes.

Q You have noted the number of the histology report, and we can see that from the previous page 429, as 96.13543. Can you tell us what you have said next to that?
A It says “- Measles – minor”.

Q Can you give any assistance as to what that would have meant? I mean, where does the “Measles” come from first of all?
A I do not know, because it is not in the clinical details.

Q If you turn back to 424a, that is the clinical details you would have been given, is that correct?
A Yes.

Q Those are the details that have been reproduced, is that correct, on to the form on 425?
A Yes, it is. I do not know where I would have got that comment “Measles” from, I do not recall.

Q Were you aware of there being some significance in relation to measles and in relation to children with autism, whose samples you were asked to look at?
A Yes. Very rarely it is said that as part of the clinical history, occasionally this sort of comment would have been made in relation to vaccination. I do not recall any being related to a definite infection.

Q What was your understanding of the relevance as far as these children were concerned with vaccination?
A The way we discussed it, it was sort of no more than the full clinical history, like this child had had pain for six months, et cetera. It was not an extraordinary discussion comment.

Q No, I am not suggesting it was, Dr Davies, but what I am asking you is that you said you recalled in relation to the children with autism the fact of vaccination being a relevant clinical detail.
A No. I have noted on one of the other reports with clinical details it did actually list the clinical details as measles vaccination.

Q Right, and on this we just see the comment “Measles”, and all I am asking you is what was the relevance of measles? I mean, you mentioned vaccination, but I was asking you what is the relevance of your note “Measles” there, and you said to me that in some cases you were aware of vaccination, and so I was asking you what exactly you meant by that, how they tie in.
A I cannot remember, I am afraid, how I generated that little note, and whether or not it was always done before the meeting, or a note to myself as the meeting continued.

Q Well, if it would have been done before the meeting, did you sometimes have clinical information which was not included on the request form?
A Yes.

Q I see. So you think you may have had extra clinical information given to you?
A Yes.

Q Where would that have come from?
A From the discussion at the meeting.

Q At the meeting. That is why I asked you that question. So would you have had any extra clinical detail before the meeting?
A No, and, as you see, some of the reports, it actually had no clinical details supplied, so it would be very important in the meeting to find out what the clinical scenario was.

Q If I can just ask you, because you raised the question of vaccination, but are you saying this note “Measles” meant measles vaccination, or are you saying it just meant measles, or you do not know?
A I cannot recall exactly how that would have been presented at the meeting, no, but I have noted that one of the other histopathology reports where the clinical details were submitted did include measles vaccination.

Q Were you aware generally, Dr Davies, were you aware of any particular interest in relation to the vaccination history of children with autism?
A I think I was aware of the general interest in measles in general within the bowel of some of the workers, yes.

Q Was that just the autistic children or was that something generally relating to inflammatory bowel disease, do you recall?
A I think it was beyond the autism. Because it was an area of investigation, it was sort of a putative agent or related in some ways in several examples of bowel disorders.

Q When you say that it was an area of investigation, can you tell us what you mean by that, please.
A I was aware of other studies that had been going on before I came to the Royal Free and were ongoing at that time.

Q Relating to what in particular?
A The epidemiology and any tissue evidence of measles infection.

Q In what condition?
A In several different examples of bowel disorders.

Q Beside the word “measles” you have put “minor”; what would that be a reference to?
A That is an overall summary of my interpretation of the seven samples submitted. I was not calling it NAD in this case but I was saying that they were minor abnormalities.

Q Returning to the note which has been made, you have said that you do not know whose handwriting that was. Bearing in mind what your notes for the weekly meetings say, can you provide us with any assistance as to when that handwritten note would have been made?
A No because I would have been unaware of the practice on the clinical side. I do not know if you want my conjecture but we did see other initials which said “seen” and was dated and I assume that the registrars would have acknowledged that they had read the pathology reports before they went into the notes but, in this instance, it has not been initialled and dated.

Q May we turn on to Child 12, please. This is again a child where your name does not appear on the typed histology report but you have recently found the list for the relevant histology meeting and again, to put that list in context, would you look at the histology report, please, which is at page 84. I should have asked you to check the name of the child against your anonymisation table.
A Yes.

Q As far as the report is concerned, was the date of receipt 6 January 1997 and print date 8 January 1997?
A Yes.

Q Under “Clinical Details” it has “Persistent (illegible)” and, if you look back at the request form which is at page 83A, can you assist at all?
A It could be “vomiting”. The secretaries were taught not to guess and only one of the pathologists would alter the clinical details if they thought it was obvious.

Q I should have said that we see this is Malcolm Ward again and the consultant again Professor Walker-Smith. If we look at the report, under “Microscopic Description”, there are four samples, 1 to 4,

“Pieces of large bowel mucosa including lymphoid follicles with germinal centres. There is no architectural abnormality and no increase in inflammatory cells in the lamina propria. No organisms or granulomas are seen”

and the signatures on that are of, Dr Rees, the trainee?
A Yes.

Q And the consultant.
A Yes, Dr Jarmulowicz. That other squiggly signature is not one of the pathologists.

Q Do you mean the one to the right of his name?
A Yes.

Q It may not even be a signature. It is just a squiggle, is it not? Did you read it as a signature?
A I did.

Q We have the list of the histology meeting which is at page 84A and we see that Child 12 is the penultimate typed name – there is a manuscript one underneath it. Is that your handwriting on the list?
A No. At the bottom where it says “22nd cancelled” I think is my writing, but the rest is not.

Q Would that be because you were on leave at that time?
A I have no recollection but, yes, it is possible or I was so busy that somebody else tried to get the meeting ready for me.

Q Can you help us as to what it says?
A Which?

Q Child 12: the handwriting beside it; there is a number and then …
A No. I do not recognise any medical terms on this. I think that it is all … I suspect that the clerical assistant has got this list together and these are all to do with where cases were and what numbers they were.

Q Now may we move on to Child 8 and the Royal Free records. Would you identify the child on your list. This is another case where your name is not on the typed histology report. Page 61. This is a report. Again, the consultant is Professor Walker-Smith. The date of receipt of the sample is 20 January 1997 and the print date is 23 January 1997. We see under

“Clinical Details

(Illegible), Diarrhoea – blood, ?mucus, colonoscopy – some …”

and is that “lymphoid nodular hyperplasia of the terminal ileum?”
A Yes.

Q If we look back at the request form, page 60A, the details which the typist could not read are “autistic spectrum”.
A It does look like “?autism spectrum”.

Q Going back to the microscopic description on page 61,

“These are both fragments of poorly orientated, but normal small bowel mucosa. A lymphoid reaction centre is seen in each sample”

and that is under I which is the terminal ileum and then II, III and IV reads,

“These are all pieces of normal colonic type mucosa containing occasional lymphoid aggregates. Minimal inflammatory changes may be the result of operative artefact”.

What does “operative artefact” mean?
A Sometimes any operative procedure, if it takes some time, will elicit an acute inflammatory reaction within the tissue before it is actually taken and ends up in a pot of formalin. So, on occasion, depending, as I said, on the length of time a specimen is handled, we can see changes which may be interpreted as non-pathological but this artefact of operative handling. It is usually more common within larger specimens rather than biopsies where obviously surgeons have taken some time in actually removing the tissue.

Q That is a report by Dr McLaughlin; who was he?
A He was another consultant histopathologist.

Q The histology meeting is one we have already referred to in relation to some notes on it. This is at page 61A. Is Child 8’s name the fifth name down?
A Yes.

Q We have already been to this because I have asked you about the “Andy” written beside it and I think you said that this is your handwriting on this form.
A Yes.

Q Can you tell us what else it says.
A “NAD” again.

Q That is “nothing abnormal detected”?
A Yes.

Q Would you turn to the clinical notes on page 9, at the bottom of the page, that confirms the meeting “Histology – normal”; is that correct?
A Yes.

Q Would you put that file away and go to Child 7, please. This is a report on which you are concerned, it is on page 149. It is not terribly easy to read but the print date is 31 January 1997 at the bottom of the page and we see Professor Walker-Smith’s name on the right-hand side. Under “Clinical Details”, I think that says “Autism”; is that correct?
A Yes.

Q Under the microscopic description – and I am now being handed a much clearer copy – it says,

“Two pieces of small intestinal type mucous with essentially normal villous architecture. There is no increase in inflammatory cells in the lamina propria or in intraepithelial lymphocytes. Part of the lymphoid follicle is included. No parasites or granulomas are identified.

Sections from all sites show large bowel mucosa with no abnormality and crypt architecture or significant increase in inflammatory cells in the lamina propria. Some of the biopsies contain lymphoid follicles. No granulomas or parasites are seen.

Comment: Small bowel biopsy and large bowel series without significant histological abnormality.”

Is that correct?
A Yes.

Q That is a report with Dr Rees, the trainee, and you participating.
A Yes.

Q Again, we have seen your table for the histology meeting relevant to these samples in the context of another child, but would you go to page 150A. We looked at this for Child 8 but, if you look down to the fourth name up from the bottom, is that Child 7?
A Yes.

Q Is that your handwriting?
A Yes.

Q The first part is an “A” by the hospital number; what does that mean?
A I do not know. There is something on the child below which is similar. I cannot recollect what that would mean.

Q Then we see “autism”.
A Yes.

Q And then, by the procedure, “colonoscopy” and again you have said nothing abnormal detected; is that correct?
A Yes.

Q You referred to the child underneath, Child 7. Is that the same letter? It is your handwriting. Do you see that as the same letter?
A It could be. I am sorry, with the photocopy, I cannot tell.

Q Would you put that one away, please, and go to Child 10, Royal Free Hospital records volume 1. This is again one where your name does not appear on the typed histology report but you found the table for the relevant histology meeting. Would you turn to page 59, please. This is in a slightly different format. I think the samples were received on 17 February 1997. Can you help me as to the date?
A I think that we would need to look at the clinical details form … Yes, 17 February 1997.

Q The clinical details are autism and diarrhoea; is that correct?
A Yes.

Q Under “Microscopic description”, we see,

“The specimen consists of small bowel and have sampled a Peyer’s patch. Where present, the overlying villi appear unremarkable. The lymphoid tissue shows reactive changes. Parasites and granulomas are not seen.”

That is the first sample. Then,

“II-VI All these biopsies show large bowel mucosa with occasional isolated bifid glands. The inflammatory population is within normal limits. Parasites and granulomas are not seen”

and the comment is,

“No significant histological abnormality.”

I would like to ask you one question arising out of that. “The inflammatory population is within normal limits” and then the comment, “No significant histological abnormality.”
A Yes.

Q What exactly does, “The inflammatory population is within normal limits” mean?
A The intestinal tract normally has an infiltrate of inflammatory cells within the lamina propria which is the compartment that you have heard about. So, within the histopathology assessment, to see if there is more than normal is a key component of trying to assess pathology in this organ.

Q And that is a report which was done again by your consultant colleague, Dr Jarmulowicz; is that correct?
A Yes.

Q You have found the histology meeting and, if we turn on to page 59AA which is the next page, is Child 10’s name the third on the list?
A Yes.

Q Again, is this your handwriting?
A Yes.

Q We see that you have written “autism” and then again that there was nothing abnormal detected; is that correct?
A Yes.

Q If we look to the bottom of the page, we see Child 10’s name again.
A Yes.

Q Is that your writing?
A Yes.

Q Can you read us what that says.
A That says, “– review ?surface change – [supplementary]”

or it would be my shorthand for “supplementary”.

Q Can you tell us what that meant.
A Like the other child, it says “Needs a ZN”. These are notes to myself to act on after the meeting. So, it would appear that, during the general discussion, I would have thought … The review was suggesting that there was some abnormality there in the surface and it warranted, in this instance, a supplementary report to be issued.

Q If we go on to 59A, is this a supplementary report?
A Yes.

Q If we look at the bottom of the page added on to the original report?
A Yes.

Q And turning over to 59B, this was done by you and Dr Jarmulowicz?
A Yes.

Q Would you have asked for his view? How did it come about you were both doing it?
A Because he was the original pathologist reporting it. As I say, it is one of consensus between people. It would be inappropriate for me to overturn another pathologist’s diagnosis without discussing it with them. And we agreed with the wording of the final report.

Q If we see what that says at the bottom of the page on 59A, under “Microscopic Description”:

“Supplementary Report

These biopsies have been reviewed following a clinicopathological meeting. The ileo biopsy shows confluent lymphoid aggregates within otherwise unremarkable small intestine. The large bowel biopsies show a very subtle scattering of chronic inflammatory cells within the lamina propria. The superficial lamina propria contains focal nuclear debris and the surface epithelium appears slightly degenerate. No active inflammation is seen. More levels have been cut and no granulomas have been identified.”

The comment is now:

“Minor abnormalities. ? [query] significance.”

A Yes.

Q So was that the conclusion the two of you reached, having reviewed?
A Yes. Also, can I just highlight this thing “more levels have been cut”. That would be if there was a suspicion on presenting the case that deeper into the tissue may furnish more information. That would often be another reason for doing a supplementary report. If a further stain was done it would again be written up as to whether that was negative or positive in some way.

Q Having done a supplementary report, Dr Davies, normally speaking, would you expect it to go into the child’s records?
A Yes, because it is part of the record. Can I just point out that the reason why page 59 is different from all the others is that this looks like a print-out from the computer screen rather than the hard copy. If you see, just above at the bottom line, where it says “Patient name,” it says “Press Return for more or ‘B’ for the previous screen”, implying that there was more information there on the computer and someone has not pressed “Return” to find the supplementary report at the time of producing this.

Q Thank you. As far as when you produced the supplementary report, how do you know when you produced the supplementary?
A Unfortunately the computer system that was in place at the time did not record that. Now the computer would be able to tell you that because you can see this copy had been printed 26 July 2007.

Q But ---
A I ---

Q Sorry. Please?
A I would assume it would have been done the day, or the following working day from when this case was discussed on 21 February 2997.

Q Discussed at the histology meeting?
A Yes.

Q And when you made your note to yourself when you were to review it?
A Yes.

Q Is this what you would have expected to happen, Dr Davies, if there was a change, on whosoever’s part, in the consensus as to the histological conclusion following the histology meeting? Would you normally expect to see a supplemental report?
A There may be minor changes of interpretation at some of the meetings but we would have discussed at the meeting whether or not it was appropriate to have full documentary evidence of that with a supplementary report. And you can see there are a handful of the examples we have of other supplementary reports being issued after these meetings.

Q You are not suggesting there are other supplementary reports in relation to the ones we have been looking at?
A No, but the other ones that have been furnished, to just show that in other cases of children with inflammatory bowel disease on occasion it was thought appropriate that a supplementary report would be issued.

Q But what would be the main reason for judging it to be appropriate to do a supplemental report?
A Really that the records were as accurate as possible because often a child would be diagnosed with something and can be labelled with that disease, perhaps occasionally inappropriately, for a long period of time. So it is important to record every time there is a discussion and a suggestion of a slight change in emphasis.

Q Just for the sake of completeness, Child 11, Dr Davies. We do not have the records for Child 11 but I think you have recently discovered a table for a histology meeting which does, indeed, refer to him. Would you go to your FTP bundle, please – not the individual records. It is bundle FTP 1, page 374a, please. Is the name at the top of that list for a histology meeting 28 February 1997 the same as the name of Child 11 on the list in front of you?
A Yes, it is.

Q Is it your handwriting again?
A Yes.

Q There does not appear to be a hospital number with this child. What would the reason for that be?
A I do not know. Some of the hospitals’ numbers are different. Very occasionally we might have had a child from the private sector.

Q I was just going on to ask you this. I think I can tell you that this child was a private patient. Is the hospital number a NHS number?
A I am not sure. I assume so.

Q We see that in any event he had a colonoscopy. What is the note that you have made beside that?
A “Melanosis”.

Q What does that mean?
A It is where some of the inflammatory cells within the lamina propria have accumulated pigment, which is likened to melanin, which is what we have in the skin. It is relatively non-specific and not highly pathological. However it is an unusual finding within the paediatric population.

Q When you say it is not highly pathological, Doctor, what do you mean by that exactly?
A In the past, this has been associated with laxative abuse, but also things like a general wear and tear pigment, so that there has been previous inflammation. This may be a late residue of this. In itself, it is not significant in terms of warranting treatment, is what I mean by highly significant.

Q Those are the details on the children as contained in their records, Doctor, and I want to ask you now a few more general questions, if I may. First of all, just in general terms, how usual or unusual is it for there to be some discrepancy between what the endoscopy report says – in other words, what the endoscopist has seen when he is actually carrying out the procedure on the child – and what the histopathologist’s report, when they look microscopically at the samples?
A I cannot give you an exact statistic for that. However, to mention that it is well-established practice that the endoscopic features, whether it be looking at the stomach or the colon, there is not infrequently a discrepancy between what the endoscopist would consider to be normal and yet have subtle abnormality when looked at down the microscope. In fact, it is a criterion for some now recognised pathological conditions for there to be a normal endoscopic appearance and abnormalities which are under the pathological umbrella of microscopic colitis, which is a term well recognised within the adult gastrointestinal clinical world.

Q Normally speaking, can you say whether the discrepancy between the two is normally that way round? In other words, that there is more to be seen when you looked microscopically than is apparent on the colonoscopy, or is it sometimes the other way round?
A Sometimes it would be the other way around as well, but of course it will be dependent upon the experience of the endoscopist, and the care and the time they have taken, and obviously their own experience. The other thing which is important to realise is that at endoscopy, quite significant changes could be seen; for example, an area of ulceration, but this type of an ulcer would not really be taken for tissue analysis because there would be very little information to gain from it. So the reverse is true, where the endoscopist has seen quite significant pathology, but the biopsies may show relatively scant change.

Q Turning if I may just to the descriptive term of ileal lymphoid nodular hyperplasia, is that a description that would be apparent and recognised a histopathologist?
A I think that is a term far more easily used by the endoscopist.

Q Is it an easy histological diagnosis to come to by a histopathologist?
A No. I think it would be an unusual pathology to suggest if one only looked at the histology. This is why the discussion is very important in terms of what is seen by the endoscopist then making sense of what we see down the microscope. It is normal within the terminal ileum for there to be prominent lymphoid tissue but I would suggest with my own time and experience of seeing some of the endoscopic features, I began to appreciate the level of lymphoidal accumulation and activity that I began to see down the microscope supporting what was seen endoscopically.

Q Leaving aside for the moment the endoscopist’s view of this when he looks at it, as far as the histopathologist is concerned, you said it can be a normal finding to see lymphoid tissue in this state. What is your understanding of whether this is a normal or an abnormal finding, when that phrase is used “a lymphoid nodular hyperplasia”?
A I am afraid it is one of degree. So at the two extremes it would be relatively easy to separate normal inactive lymphoid tissue and massively hyperplastic lymphoidal tissue, and I am sure there would be debate in the grey area of what is acceptable as normal and what is somewhat beyond abnormal. It is something, however, that is far more frequently seen within the paediatric population than within the adult population, and also the prominence of the lymphoid tissue itself is more prominent throughout the intestinal tract within the paediatric population.

Q Generally speaking, how would you describe it? Would you describe it as a subtle finding, an obvious finding, somewhere in between the two?
A I think I have seen examples of both.

Q Turning to The Lancet paper which is a relevant issue with regard to Dr Davies, can you tell us at what point you ultimate saw a copy of this paper? You told us it was prior to publication.
A When it was in a draft format.

Q Can you remember how it came about that it was decided to write it up?
A No.

Q Your name has been included on it. Were you any part of the decision to write it up?
A No.

Q And you said you saw it in a draft form. Is that correct, before publication?
A Yes. Can I just point out that my name is on several papers with paediatric gastroenterology slants, and at no time did I take a decision that these children were being written up. It was just part of our common practice, really, that some children would be in different type of management trials, therapeutic trials and occasionally I would review all the histology. On others it would be taken from the meeting. It was not an exceptional incident.

Q I was not suggesting that you made the decision, doctor. I just wondered whether you could assist us as to when the decision was made.
A That I cannot tell you.

Q And who would have made it. Someone has to take the initiative and write the paper, do they not?
A The senior authors, whoever wrote the first draft. I do not know what time that would have occurred.

Q When you saw the draft of the paper, when you were given it, before you read it, did you know who had drafted the histology part of the paper?
A It was my understanding that it was Dr Anthony and Dr Dhillon.

Q How did you understand that?
A Because I know I had not written it and it listed in some detail the histopathological features and I was aware that there were other sections that Dr Anthony had ---

Q That is the next question I was going to ask you. What access did Dr Anthony have to the biopsy material? You have told us how it was sent to you and you have told us that on occasion sometimes it was sent separately as a research tool.
A There is another way as well and that is with the specimens that we received, it is normal to take several sections from each piece of tissue. This is what we call levels. So there would be several levels and you can put the sections onto two glass slides: one kept within pathology, another set being taken for research purposes.

Q If that happens, someone has to carry that out: the technicians presumably in the histopathology department.
A Yes.

Q Were you aware that that had happened in this case?
A I am not sure if these were consecutive sections taken from the pathology samples or separate tissue samples taken at the same time, but they would have been – I would assume they were all processed and cut within the histopathology department and the generation of the glass slides.

Q Did you in fact make inquiries about whether and how Dr Anthony had obtained samples?
A No.

Q At a later stage?
A No. I knew they existed and I think on a rare occasion I actually asked to see some of his sections of some children.

Q Do you mean some of these children?
A Children in general.

Q When you were given the draft of The Lancet paper, did you read it?
A Yes.

Q What was your overall view of the terminology used in relation to the histology findings in The Lancet paper when you read the paper?
A I was somewhat concerned with the use of the word “colitis”.

Q First of all, what did you understand that word to mean?
A I personally use the terminology “colitis” when I see active inflammation or a pattern of changes which suggest a specific diagnosis. It was not my impression that the children coming through in the spasmodic way that they had, that I had formulated a sense of a distinct pattern warranting that terminology.

Q You said you were concerned. What was the nature of your concern?
A As I have explained, the use predominantly of the word “colitis”.

Q Did you raise the nature of your concerns with Dr Anthony at the time?
A No.

Q Why was that?
A Because I discussed this with Dr Murch.

Q Are we still talking prior to the publication of The Lancet paper, Dr Davies?
A Yes.

Q You discussed it with Dr Murch. Was he able to allay your concerns?
A I was concerned that what we had seen in these children was relatively minor changes and so I discussed this with Dr Murch and I think we decided between us that it would be a good idea for me to review some cases blind and with controls.

Q Before you go any further, Dr Davies, remembering you have a Panel with lay members on, what do you mean by “blind” and “with controls”?
A Obviously I open my eyes, but I am blinded to what the diagnosis is, what the endoscopic findings are. So if you like, it is just the pure morphology, which is a word we used earlier: what is the pattern of changes in the tissue itself telling me? The control group was children with disease and children without disease. Again, I was blinded, not knowing who any of these were, made notes myself and tried to separate out into groups who had abnormalities within the tissue and who did not.

Q This was a review you did of these slides as a result of the concerns you had raised with Professor Murch. When did you carry this out? If I can assist you as to the date of the publication of The Lancet paper, that was February 1998. That is when the paper was actually published in The Lancet. I obviously cannot tell you when you saw a draft, but I just want you to cast your mind back to then and tell us when this review which you did was carried out was.
A I do not believe I dated it.

Q No, you did not, which is why I am asking you. This is not a memory test.
A The only way we could work it out is because the pathology of the children in question were all taken in a relatively tight timeframe, so they were all contemporaneous ones going through the paediatric gastro department at that time.

Q Let me take you to your notes of the review, Dr Davies, so you can look at the dates of the samples. If you would go to FTP bundle 3, please, page 1110, are these your notes of the review which you undertook?
A Yes. These are photocopies of them obviously.

Q We have the originals. Would you prefer to look at those?
A Yes, please. (Same handed) However, from the pathology identifying number, I can see we have several from the end of 1997, perhaps midway 1997, I would guess. Something like 1997.7080 would have been about July/August and we have some in 1998, towards the beginning part of the year. So presumably I reviewed these biopsies in mid 1998.

Q Mid 1998?
A That is my suggestion, yes.

Q Could it have been the case that in fact you did your review after the publication of The Lancet paper?
A No.

Q We know The Lancet paper was published in February 1998, Dr Davies. Can you tell us, if we look at the 1998 patients, how can you tell when in 1998 they were?
A There is not a time, but it is just that the numbers go from 1 in January. I am afraid it must be the case that I obviously reviewed them after.

Q After the paper?
A Yes.

Q I appreciate you are having difficulty with your recollection, but now you have seen that, can you just cast your mind back and tell us why it might have been that you would have been expressing concerns with Professor Murch and undertaking this review as a result of it after publication of the paper, if that is indeed the case?
A Just the use of the terminology implied to me something more specific than my recall of the children with the pathology which the children with autism had.

Q That was the reason why you say you did it?
A Yes. I wanted to alleviate in my own mind.

Q Alleviate - ?
A Any concerns I had in terms of the justification of some of the terminology for the histopathology.

Q In relation to the samples which you did this review for, you have told us you were blinded, but you knew there were some controls. So you had some which were from some children and some which were controls.
A Yes.

Q Where did those samples come from?
A I am sorry, I am slightly confused by my own interpretation of my actions, because obviously I was incorrect in that. The list of children to look at came from Dr Murch, because he would have known the final clinico-pathological diagnoses and I had to stay blinded to them, so I could not use my computer to generate a list.

Q Professor Murch gave you a list without any names or any information; just a list of the slides you were to look at. Is that correct?
A I had the name and the pathology number.

THE CHAIRMAN: I think Dr Davies’ concentration is starting to waiver. I just wonder whether you would like a few minutes’ break.
A It is okay.

THE CHAIRMAN: Are you sure you are able to continue?
A Yes. I am just realising I am not as sure of some things as I thought I was.

THE CHAIRMAN: It is difficult to cast your memory back ten or 11 years.

MS SMITH: Professor Murch gave you a list and you say you think the list would have had names on.
A It would have had the name and the pathology number. Every slide in the department – the histology slides do have the number, but also the name, to double the chance of correct identification. That is why we had that.

Q If we look down these names, we see on what is my second page, page 1111 in the bundle, the fourth name down, which begins with an “S” and ends with an “R”. Do you see?
A Yes.

Q That is a child who is not a Lancet child, but is a child whom this Panel are having to consider. There are no names of any children who are part of The Lancet paper in this list of names. Is that correct?
A Yes.

Q As far as you were concerned, Professor Murch was supplying you in this blind review with some children who had autism and some who did not as controls. Is that correct?
A Yes.

Q Why is it that you did not review in there the actual slides relating to The Lancet children?
A I cannot remember any specific discussion we had about it, apart from to exclude them, but I think to keep me blinded as to who was who, they were all of the same timeframe and The Lancet children are from much earlier and so I would have immediately spotted that the pathological numbers, the histology numbers, were from a different time and it would have put a bias into my interpretation immediately.

Q Did you think at the time, Dr Davies, that the children that you were given to review included Lancet children, or did you think they did not?
A I do not think we discussed it to the level of definite exclusion or inclusion.

Q I understand that, but at the time, can you recall, did you think that some of The Lancet or all of The Lancet children were included?
A At the time of my review, I think it is safest for me to say I cannot remember if I assumed some would be The Lancet children or not.

Q You have told us that the reason you were doing this was because of concerns in relation to the histopathological report by Dr Anthony of The Lancet children.
A Yes. I was concerned in terms of the terminology used in relation to the children with autism and their bowel. So to me, it was a similar cohort of patients that were being looked at: they presented in similar ways, had been analysed in similar ways, and so for there to be – I do not know how many I looked at – 21 children with autism and with bowel symptoms, I would have assumed they are all within the same cohort of clinical practice.

Q Do you recall the nature of the discussion that you had with Dr Murch which led to his actually giving you the names of the children to look at?
A No, I cannot remember the day, or who said what, or why, but it would just be a general discussion of how to go about this.

Q Well, since these are not The Lancet children, I only propose to go through them briefly, Dr Davies, but if I can just return to the first page of these at 1110 and just ask you, first of all, going through what each column means, the columns are headed “Chronic”, “Surface”, “Active”, “Architecture” is that?
A Yes.

Q What are they references to?
A “Chronic” would have been my assessment of the chronic inflammatory cell infiltrate, which is the normal cellular component within the lamina propria.

Q Just in broad terms, “Surface”, what would that have referred to?
A “Surface” would have been taking particular attention to the surface epithelium and again inflammatory cells there. “Active” is related to neutrophils or polymorphs to the cells involved with active or acute inflammation, which, in my opinion, is never normally found within the bowel. “Architecture” is an assessment really of significant, often chronic, inflammatory changes within the bowel, which is a very important feature in the assessment of inflammatory bowel disease, by which I mean Crohn's disease and ulcerative colitis.

Q We have seen how, when we look at individual histopathology reports in clinical practice, there are a number of samples taken from different sites. When you did this review were you only looking at the one site?
A I only looked at one site, which was specimens from the transverse colon.

Q Yes. Then the next column along after “Architecture”, is that “Comments”?
A Yes.

Q What does that contain? Your comments at what stage?
A That is the comment that I generated from this obviously one slide in terms of the morphology, so the morphological features, what would I be thinking of, which then would be part of the clinical pathological work up to make a diagnosis; what would I be suggesting on the tissue alone was going on in them.

Q That is the bit that you did blind, is that correct, without knowing any details?
A Correct.

Q Then in the last section we have “Clinicopathological diagnosis”. When was that information provided?
A In the original this is a different colour ink done at a separate time, and this is when I was being unblinded, with Dr Murch telling me which disease category each of the children’s biopsies came from.

Q Right. If we go to your last two pages, Doctor, which have got the darker writing on the right hand side.
A Yes.

Q Whose handwriting is that in the darker ink down the far right hand side, which starts off “16/21 autistics”?
A I believe that to be Dr Murch’s writing.

Q Does that continue on through the next last page?
A He has written on the reverse of one.

Q Oh, is it, in the original; we have it as two separate sheets. Does it start off with the words “8 colitis” and end up with the words “1 Crohn’s”?
A Yes.

Q I just want to run through, if you could with us, just translate what those notes down the side are saying in relation to when you were unblinded on this review, Dr Davies. I mean, first of all, at the top, what does it mean “16/21 autistics”?
A Well, you can see from the sixth column, where we have put the clinical diagnosis, I have written the word “Autistic” 21 times, meaning that there were 21 children with a final diagnosis of autistic bowel abnormalities I looked at, and of those, on blinded review – sorry, I identified 16 which I considered to be abnormal.

Q Yes.
A Likewise, that is the same for the other control groups.

Q Right. Of the five autistic samples which you thought were normal (in other words 16 from 21), can we see what your comment was written beside that, where Professor Murch has put “5 not”?
A Yes. One of those had melanosis. Another two had prominent lymphoid follicles. Another two were sort of “normal normal”.

Q Then we go on to “LNH”. What is that referring to?
A This would have been again the lymphonodular hyperplasia but without other features in the colon that were identified in children who did not have autism. So again this is predominantly an endoscopic and clinical category.

Q We see under that the details of those, is that correct?
A Yes.

Q “1 [with] melanosis. 1 ‘colitis’. 2: slightly abnormal. 3: excess lymphoid tissue. 3:” – what is the last one?
A Excess eosynophils.

Q Thank you. Can you go on with the translation, rather than me. I mean, I am very happy to take you through it, but---
A Actually, I do not think the numbers add up correctly. I did do 54. The “normals”, there were eight, I believe, and I considered five of those to be normal, and the other three, one had minor excess chronic, two had diffuse mild excess chronic inflammatory cell infiltrate.

Q Right.
A Again, as Dr Murch has written there, “? Post infective” for one of those, I think subsequently this child was found to be post infective, which would have explained that subtle abnormality.

Q Yes. Then on to the next page.
A “CD” is Crohn's disease, which is a very important category of inflammatory bowel disease. You see there are no ulcerative colitis patients within this group, because on morphological grounds we thought I would be able to identify those and so would not be blinded to them, and so we only looked at Crohn's disease.

Q Are they on the back sheet?
A Yes. I was trying to find the sum total. I think it was fifteen in total, and eight of those I classified morphologically as having colitis, five only slightly abnormal and two “normal normal”.

Q Thank you. Then underneath that we have a note - is this also by Dr Murch - which says “Samples initially chosen from [pathological] reports”, is that correct?
A Yes.

Q “Assessed in blinded fashion to determine whether [diagnosis] of colitis. Normal or bowel mild abnormality.”

A That might be “showed mild abnormality”.

Q Thank you. So they are what you were looking for, is that correct?
A Yes.

Q Samples were chosen and then assessed in a blinded fashion to determine whether there is a diagnosis of colitis, whether they were normal, or whether there was a mild abnormality?
A That might even be “sig” – significant colitis.

Q Thank you. Then the remainder of the words, and I am not going to complicate matters any more than they are already, Dr Davies, the remainder of the words on that page, do they relate to a different research project that Professor Murch was involved with?
A No. These were more of the surface changes. Where I have just said “Surface”, there are sort of four components I would have in particular been looking at.

Q Right. I see. Well, in that case you had better deal with them. What does it say, please?
A “Nuclear dust and debris. Sometimes intraepithelial. Nuclear condensation.”

Q “Prominent in 6 autistics” is that?
A Yes, “1 normal. 3 LNH. 1 Crohn’s.”

Q So that was relevant to your findings?
A Yes.

Q Now, we have established that those children were not The Lancet children, if I can use that as a composite term. Did the findings that you made in that review, Dr Davies, lead you to have to amend any of those children’s clinical histology reports?
A No, because I did not review these slides with the histopathology reports, because obviously I would have been unblinded if I had the reports.

Q No, I understand that, but when you have been through them with Professor Murch and you had unblinded them, did you, or as far as you are aware did you have any conversation with Dr Murch about whether it was necessary to go back and rethink any impact it might have on these children’s clinical care?
A It is not my recollection that we did that, no.

Q I mean, are these the sort of findings that you have come up with here, that you have observed here, are they findings which might have an impact on the actual care of the child?
A No, because the contention had been that some children with autism seemed to have some subtle abnormalities within their bowel, and although the decisions of management of that would have been very difficult, this was the main group of interest for this review, and the review supported that there was a subtle abnormality in the majority of children presenting to the paediatric gastroenterology department with a diagnosis of autism and often with some bowel upset.

Q I understand, but I just wondered whether, having discovered that subtle abnormality, you had any discussions as to whether in respect of these children whom you looked at, when you saw those subtle abnormalities, whether they impacted on clinical care at all?
A Well, I do not assume that the histopathology reports were particularly different from my review.

Q Did you feel that that review had any relevance in relation to the findings with regard to The Lancet children?
A It was mainly to set my own mind at rest and to be able, in terms of teaching and postgraduate education, to be aware of the pattern of change that you would see in such scenarios. When you do things one-off on a day to day basis of diagnosis, it is quite difficult to get an overall picture. You do need to do formal review altogether, looking at everything in a systematic manner, to be able to pick up subtleties of patterns.

MS SMITH: I wonder if it might be a convenient moment now, sir, to have a short break.

THE CHAIRMAN: I think it will be. I am actually obviously quite concerned to make sure that Dr Davies is able to continue to give evidence. We will now adjourn and resume at 10 minutes past 4. That will give you an extra four or five minutes to refresh yourself, and I am sure somebody will look after you with a drink, but once again, Dr Davies, you are still under oath and still in the middle of giving evidence, so please do not discuss it.

(The Panel adjourned for a short time)

THE CHAIRMAN: Ms Smith, would you try to wind it up between 4.00 and 4.45 if it is at all possible.

MS SMITH: Yes, sir, of course. (To the witness) I am going to ask you to deal with a last child and, just to fill you in on this – the Panel know it – there is a child who is referred to as Child S in one of your histology meetings but who is not part of The Lancet children to whom we have been referring as JS, his initials. I want to take you to the histopathology records in respect of him in case we need them for some reason. Would you look at the records for Child JS and it is the Royal Free Hospital records. This is again a case where you are not named on the clinical histology report for the child but you have a table for histology meeting and we see his name listed. Would you turn first of all to the clinical histology report, please, which is at page 32. In fact, it goes backwards. So, the final page is on page 31. We see the date of the receipt of the sample as 14 November 1997 for this child. The consultant is Professor Walker-Smith. The clinical details are, “Autistic spectrum with diarrhoea/constipation [and] abdominal pain” and then we have the microscopic description,


Unremarkable small bowel mucosa including prominent lymphoid tissue. There is no diagnostic pathology present.


Unremarkable large bowel mucosa.


Large bowel mucosa in which there are small foci of cryptitis and crypt abscess formation (the latter in III)” in other words sample III. “There are no granulomas present.


Normal large bowel mucosa.

The features are of a mild patchy non-specific acute colitis. Follow-up is advised.”

That is a report by a Dr Levine. Can you help us as to who he is.
A It is a she. She was also a colleague, a consultant histopathologist. She arrived after me within the department. In terms of the phraseology, it may be slightly different from the way generally these cases would have been reported.

THE CHAIRMAN: Dr Davies, would you pull the microphone a little closer to you.

MS SMITH: I am awfully sorry, Dr Davies, but I was going to ask you to do the same thing. I am afraid that I did not hear what you said.
A Dr Levine was also a consultant histopathologist who arrived some time after I did in the department and did this on her own. The terminology is perhaps slightly different from some of us who had been there before would have used.

Q Can you tell us what particularly you mean. What about the terminology are you particularly referring to?
A Acute colitis would have been a little unusual.

Q When did Dr Levine arrive?
A That I cannot tell you off the top of my head.

Q The histology table which went after that is at page 32A. Is Child JS the third on that list?
A Yes.

Q Is this your handwriting again?
A Yes.

Q Would you go through the notes for us, please.
A It looks as though I have said “distal active colitis”.

Q Is that “active?
A I think it is a-c-t.

Q Is that your writing where it says “autism” in the middle?
A Yes.

Q Would you have taken that from the clinical notes?
A Yes.

Q We see the details on the page before, page 32.
A Yes.

MS SMITH: Sir, as is the way of things, that was a rather shorter time than I was expecting it to be. I only have one other topic and I will not be that long with it; it might be half-an-hour or it might be shorter depending on the answers.

THE CHAIRMAN: Well, if it is up to half-an-hour …

MS SMITH: Sir, may I respectfully make a suggestion? If it is going to break in the middle, I would prefer to deal with it tomorrow morning because I am going to put in a table, there is some explanation of it and, for your own purposes, you would find it clearer if you went through it all at once, which is why I was going to put it off because, as I say, I was expecting this to take a little longer. As I say, that is the last topic that I am going to be dealing with and I do not anticipate it taking more than half-an-hour if as long as that.

THE CHAIRMAN: I would prefer that it was done in one go. I look towards the Panel members. (Pause) I think that we will call a halt now. Obviously there are difficulties with transport arrangements this afternoon.

MS SMITH: I am very conscious of that for all of us.

THE CHAIRMAN: We will now adjourn until hopefully as near to 9.30 as possible tomorrow morning depending again upon the travel arrangements for some of the members and of course Dr Davies as well.

(To the witness) Dr Davies, it is never an appropriate thing to leave the witness overnight under oath, but I am afraid that we have reached a stage when we have no choice but to do that. You will be under oath. You are still in the middle of giving your evidence, so make sure that you not discuss this matter. You are not forbidden to talk to anybody just as long as you do not discuss this case.
A I understand.

THE CHAIRMAN: Thank you very much, indeed. We will now adjourn and resume at 9.30 tomorrow morning.

(The Panel adjourned until Wednesday 5 September, 2007 at 9.30 a.m.)

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