Thursday, February 2, 2012

Day 39 GMC Fitness to Practice hearing for Andrew Wakefield



Wednesday 3 October 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


Cross-examined by MR MILLER, continued 1
Re-examined by MS SMITH 20
Questioned by THE PANEL 32
Further re-examined by MS SMITH 39

THE CHAIRMAN: Good morning to you all. Mr Miller, you were in the middle of the cross examination.

Cross examined by MR MILLER, continued

Q Professor Rutter, you accept, I imagine, that research and service, clinical care, can run in parallel?
A Certainly.

Q In fact it is good practice – I think one of the lectures that you gave talked about the inter relationship between research and clinical care and that both needed each other to keep going?
A Yes, indeed.

Q On its most general level you have seen the general consent to research biopsies that appear habitually to have been given in these cases which permitted extra biopsies to be taken?
A Yes.

Q Material can be obtained from patients who are in fact being seen on the basis of clinical need providing care?
A Yes.

Q That, whether it is right or not, the Committee is going to have to decide. But, that assumption seems to have been made in relation to the application that was made to the ethics committee because, on the face of the application, it says that they would be having these investigations anyway as part of clinical care?
A Yes.

Q That, as we saw yesterday from the letter from the Chief Executive of the Trust, was his understanding as well. So the real question in this case may be whether or not what was done in each case represented clinical care or research?
A Yes.

Q On the medical aspect of that, or the clinical aspect of that, perhaps the next witness may be able to deal with that in more detail than you because he is going to be talking about the procedures that were carried out in the gastroenterology department?
A Certainly.

Q You have looked overall at the material which was placed before you and, on the basis of that material, you expressed the view that these admissions and the investigations were research driven. I just want to test that hypothesis in looking at some of the cases to see how much what one can rely on particular features which you have highlighted. I am not going to go through all the cases again, I just want to look at some of the cases because you have highlighted particular parts of the case and said, “That suggests to me this is research rather than clinical care”, so we will just go over a little of that ground. You will be relieved to know I am not going to go over all the cases again.

The only one I want to spend any time with is case 2. In that regard if you could have the Royal Free Hospital notes for that patient available. If you could start by looking at page 8. The pattern of your examination in chief was that you were asked in respect of each child, having gone through the notes and correspondence, to give your opinion from your point of view whether you thought it was a clinical care or research case. We can just go back over some of this because you did make some observations in this case which we need to test.

First, on page 8, it looks as though this child was seen first on 1 September by one of the consultants, Dr Thomson, because his is the first note here for 1 September. It says:

“Admitted for colonoscopy and Schilling test
H/O [history of] neurological regression
3 x obstructive jaundice episodes

Multiple medical input.”

Presumably that is a reference to what has happened already in the past?
A I presume so.

“Due to see [Great Ormond Street] for metabolic workup
Seen Dr Robert Surtees (James Leonard Department).”

He is the paediatric neurologist.
A Yes.

“Need to contact [Great Ormond Street] with metabolic work up especially in view of CSF pre lumbar puncture.”

Later on we will see that, in fact, contact was made with Dr Surtees because a fax came over from Dr Surtees with a copy of reports that had been generated quite recently from Dr Casson. I think Dr Surtees’ own report was there as well. I know you made a comment in relation to some of these children that there did not appear to be any liaison with the people who had been involved before, but, clearly, there was contact to Dr Surtees which produced that documentation from Great Ormond Street?
A Yes, indeed.

Q Starting on page 15, and I think some of it gets out of order but we do not need to go through it, there is a note which we have taken to be dated 2 September 1996, which is a long and detailed admission note effectively from the lecturer, Dr Casson, which gives – and you have been through it – a full and detailed proper history of the signs and symptoms this child has, the record of the examination that he carried out and the history in some detail, not only the family history but also of what happened in the past as far as this child is concerned. On the face of it, it looks like a good clinical admission note, does it not?
A Yes.

Q As we have seen, there was concern about contacting Dr Surtees and that appears to be, on the note we looked at from Dr Thomson, by reference to the lumbar puncture and the metabolic workup that was going to be considered by Great Ormond Street?
A Yes.

Q If we look at page 152, the fax from Great Ormond Street, it comes from Dr Surtees and it contains, as you have already agreed, the Dr Hilary Cass letter. Written on the front of the fax sheet it is written:


protein electrophoresis
measles [antibodies]
lactate, pyruvate, glucose.”

I am not suggesting that has been written by Dr Surtees, I am just identifying that those are the CSF investigations that somebody is suggesting at that time?
A Yes.

Q If you would turn to page 351, Mr Hopkins took you to this document yesterday, “Investigations for Possible Degenerative Disorders of the Central Nervous System”, and you said that if you are investigating anyway, an aide memoire or a check list is no bad thing because it makes sure you do not miss anything out?
A Yes.

Q We see under the CSF, towards the bottom of the page, the same four out of the five which were listed on the fax sheet, protein electrophoresis, lactate, pyruvate and glucose for the CSF. Do you know the purpose of testing the CSF in this way for protein electrophoresis lactate, pyruvate and glucose?
A Those would ordinarily be in terms of a progressive encelopathy of one kind or another.

Q That would be some degenerative condition of the brain which might be giving rise to whatever symptoms the child would have?
A Yes.

Q I think you accepted that if you are looking at the cerebral spinal fluid for that reason you are looking for an explanation for behavioural changes or developmental changes in the child, but not for autism?
A Yes.

Q We see, Professor, and I do not think I need to take you to it because you already have seen it, that these investigations were done and, according to Dr Casson’s note, these investigations under the CSF in this case were carried out?
A Yes.

Q Can we turn to the discharge letter which starts at page 145 in that same bundle.
A Yes.

Q Ms Smith went through some parts of it with you, but, because you were only commenting on the neuropsychiatric and neurological aspects, she did not direct your attention to the gastrointestinal history, signs and symptoms, or the results of the colonoscopy or histopathology. That is fine, as far as it goes, but obviously it is of some relevance to the overall picture of the case, is it not, because this document is emanating from a psychiatric gastroenterology department?
A Yes.

Q The fact that Dr Casson is reporting back to the general practitioner in fairly detailed terms about what the findings of the gastroenterological investigations were is important in looking at the overall picture of the case, is it not?
A Yes.

Q She also passed over the reference to treatment in this and, indeed, I think in most of the other discharge letters. But it is clear that in this case, and in most of the cases which you have reviewed, having investigated these children and obtained histology evidence and the results of the colonoscopy, the paediatric gastroenterology department was advocating a particular type of treatment in almost every case – in fact, in every case ultimately – and in some cases that treatment kicked in later, after an outpatient review.
A Yes.

Q The penultimate paragraph on page 148 reads:

“With regard to [Child 2’s] neurological problems, an opinion of a neurologist and a child psychiatrist have also been sought. I am sure that they will forward further information to you.”

So, by the time Dr Casson wrote his letter, it looks as though those details were not available.
A Yes.

Q Then:

“We will review [Child 2] in clinic in two weeks time. As with all children who start on [a particular type of] enteral feeding regime he will need a repeat colonoscopy after having been on the diet for 8 weeks. We will also need to arrange an upper endoscopy in the near future.”

Out of that letter comes, first of all, a description of what his understanding of the history was – which, again, you would expect from a discharge letter after a child has been in as an inpatient; secondly, what the findings were from a gastrointestinal point of view; and, thirdly, the suggestion of treatment and follow-up.
A Yes.

Q Which looks pretty much like clinical care, does it not? On the face of it, this letter looks like a conscientious doctor in training reporting what the findings were and the recommendations to the parents about how this child is to be treated.
A So far as the gastroenterology side is concerned, certainly.

Q Because the neurological psychiatric evidence is not available to Dr Casson, he says that will come later. As far as this aspect which he is writing on, it looks purely clinical care, does it not?
A From a gastroenterology side, but I come back to the point that this is the one case where there clearly has been not only one marked regression but several, so that that is the crucial part of the clinical problem, and what is very striking is that that was not assessed. It is true that reference is made to something being done later, but not part of it, and the founding history is not followed through at all.

Q But that would not be followed through by Dr Casson, would it, or by the gastroenterologist? That would be followed through by Dr Berelowitz, if he was involved in the case.
A Yes. But, given the importance of the regression in this case – and I do accept this was an important regression and, as I have already said, I think vigorous investigation was indeed justified in this case – so I do not actually criticise that – what I do criticise is the fact that the investigations were done without planning or consultation with somebody who is experienced in the area.

Q I am going to accept that in a moment but it is not quite the point I was addressing. You say it is all “the cart before the horse” and, secondly, that one needed an expert to do a structured assessment of this child to make a definitive diagnosis. That is your criticism.
A More than that, that one needs to have a proper assessment which had not been done.

Q Yes, to make the definitive diagnosis, you needed a proper assessment.
A Yes. Let me make quite clear that in terms of the follow-through on the gastroenterology, so far as I can see, as a non-expert in this area, I have no criticism to make. Obviously I am not expert in the investigation and I cannot comment on how far those were justified, but I certainly do accept, going through the records, that that side of things, as you quite rightly say, often – perhaps always, I do not recall – led on to some kind of therapeutic plan.

Q To the extent that there was a report back in each case – sometimes later, sometimes earlier ---
A Yes.

Q --- from their point of view, on those investigations, they look like clinical care reporting back to the appropriate people, the general practitioner or other referring consultants.
A So far as that aspect is concerned, yes.

Q Just on that point, if you look at the recipients of that letter on page 149.
A There are dozens of them.

Q There are dozens of them, but they are people who have been involved. You made criticisms about people not being kept in the loop or being contacted, but clearly everybody who has been involved over a period of time is told about this and what the plans are.
A Yes.

Q I am going to come back to one small aspect of that case in a moment. Perhaps we could look at the consent forms. At page 340, you accepted, I think, when this was shown to you by Mr Hopkins, that this was probably the standard clinical consent form at the time for investigation.
A Yes.

Q You have looked at the other “general” research consent form – which, again, I think is, in most if not all of the cases, the one for the taking of the two extra biopsies. Again I do not want to take time looking at that, but you have seen that and you accept that that is a different type of consent form.
A Yes.

Q In this case, at page 338, we have a research consent form of a different type, which relates to the entry of this child into a cohort study into evaluation of enteral nutrition.
A Yes.

Q Which I imagine you would say is a research consent form of the sort you would expect if children were being entered into a trial.
A Yes. The information sheet – which is the crucial thing with any consent form – is not there. It is actually very difficult to know what they have agreed to.

Q That said, the important thing is that the consent form annexes the information sheet, a copy of which is given to the parents in this case, and it has been explained what that research is.
A Yes. But it is dealing with the role of polymeric nutrition in children with Crohn’s disease, which is actually not the problem here.

Q It is not which problem?
A It does not deal with the regression and the neurological side and it focuses on Crohn’s disease.

Q Yes. I was not putting it to you as if this were a consent form from the Project 172-96. I am saying this is an example of a case.
A Yes.

Q Please do not think I am saying this covers the regression point, it is just an example of the different type of consent form for entering into a research trial.
A Yes, that I do accept.

Q Whereas it was considered appropriate when this child was admitted simply to give the general consent form for the investigations that were carried out, when it came to a clinical trial, enteral feeding, it would have generated a different type of consent form.
A Yes.

Q This child had to come back for a follow-up colonoscopy because, after a period on this trial, they had to look to see what if any difference it made to his bowel pathology.
A Yes.

Q He was readmitted, I think in November, and we will come to one aspect of that in a minute. There are certain features of his case which are mirrored in most of the other cases, are there not? So far as the gastroenterology side is concerned: (a) the detailed admission note, mostly from Dr Casson; (b) the investigations – which you have seen, although they may not have meant very much to you; (c) as far as Dr Davies is concerned – the histopathologist, whose evidence you have read – a final meeting at which everybody thrashed out what the findings were; and (d) the discharge letter from Dr Casson explaining what the findings were and treatment. These are features which are common to most if not all the cases.
A In those respects, yes, although this case is different in umpteen other respects.

Q I know this case is … I will not say your “flagship” but it is the one where it gets closest to disintegrative disorder, although it is probably not.
A Yes.

Q That is the only case I am going to go through in any detail. I want to pick up a couple of things which you say are pointers to the fact that this was research driven. You were asked to comment on individual cases and said, “I think this shows that it is probably more likely research than clinical care.” One of those statements related to the absence of outpatient clinic appointments. You will remember you said, when you were dealing with a particular case, “If this was clinical care, I would expect there to have been an outpatient clinic appointment first when an evaluation of the child would take place.”
A Yes.

Q In relation to the one that you were considering at the time, you said, “There is not an outpatient clinic appointment here, which makes it look more like a research admission rather than a clinical care admission.” You are nodding your head.
A Yes. Obviously I am not saying that you cannot have clinical care without a prior outpatient appointment. What I am saying is that ordinarily the decision as to what you do clinically is driven by sorting things out as best they can at an outpatient level.

Q I think you said you would expect, if the patients were being seen on the basis of clinical need, that there would be an outpatient clinic appointment and you identified the cases in which there were. In fact, as far as we can see from the cases which we have here, it only applied to Child 4 and Child 8, who just happen to come from the same area, XXX, which is about as far away from London as you can get in mainland England. If that factor, the fact that they did not have an outpatient clinic appointment, points towards research rather than clinical care, what about the other nine cases where there was an outpatient clinic appointment conducted by Professor Walker-Smith. What is the strength of this observation that it looks more like research than clinical care, if nine out of eleven did involve an outpatient clinic appointment conducted by Professor Walker-Smith?
A As I have said several times, in sorting out whether it is clinical care or research, no self-respecting clinician or scientist would go on one item, and I have certainly not done so. Of the items I have mentioned, I would place least weight on this particular one. In this particular instance, sticking with case 2, what is striking is that the family was already involved in litigation at the time, and that played, in terms of the families concerned, a key role in their wanting to be seen. There are several different elements. The presence or absence of an outpatient assessment would be one feature but it is not one on which I would place much weight.

Q It would be quite difficult to place much weight on it in view of the fact that nine out of 11 did.
A As I say, I do not place much weight on it.

Q I know, but, if anything, you would have to place the weight the other way, which is the fact that in those nine, since there were outpatient clinic appointments, it is more likely that it is clinical care. It cannot be just negative.
A No, but we have to come back to the fact that the whole of this is involved in looking at the co-occurrence of two key features: gastroenterological problems and possibly neurodegenerative problems, so that the assessment needs to be involved with both. I do accept the point you have just been putting to me, that on the gastroenterology side this ordinarily had been looked at in a way that I would see as comparable with clinical care. From the neuropsychiatric side, I think that is strikingly absent.

Q We went over this yesterday and I do not want to take too much time on it again but I think you accepted when I put it to you that you appeared to have quite detailed, extremely detailed investigations on the gastroenterological side.
A Yes.

Q But as far as the psychiatric and neurological side was concerned, a fairly light input, identifying not a definitive diagnosis but whether or not these children fitted into a fairly wide category of autistic syndrome. That is what it looks like. I take, although I do not think it makes any difference, your criticism as to the way in which those assessments took place and the timing of them, but, looked at overall, that appears to be the balance, does it not? The psychiatric and neurological aspect was … I will not say ticking the box, but simply saying “I confirm that this child does come into this broad general category”.
A Your phrase is, indeed, an appropriate one. It was, basically, nothing much more than ticking the box.

Q I am not arguing with you about that. If you are looking at it overall, you do not find, and it is difficult to look for, a complete balance between the work-up on both sides. Quite clearly the gastroenterological side was very carefully assessed, but, as Dr Berelowitz made clear, I think in that first letter, the Child 2 letter: “I am not here to provide clinical care, to make a diagnosis, I am here to confirm, effectively, whether or not it comes into this area.”
A Yes.

Q The next thing I wanted to ask you about was following up abnormalities. Again I do not want to go through all the cases and look to see whether we can find if abnormalities cropped up and whether they were dealt with or not, but you say that if abnormalities did arise in any particular case you would expect, if this was clinical care, that they would be followed through.
A Yes.

Q You gave the example of lead and pointed to the fact that in some cases there did not appear to be any follow-up of the lead level.
A All but one, yes.

Q If you look at Child 2 (and you have got that file there still, have you) at page 22, this I think is on the readmission of this child in November. Do you see in the middle it says blood lead of 120 micrograms per litre and the range of 100 or the normal is less than 100. Then on page 23, the next day, at the bottom of the page, 11/11/96, ward round, Professor Walker-Smith and the last line on that reads: “Contact lab about lead levels” – there is an arrow up. We do not see where it goes, or at least I have not found where it went, but at the ward round it is suggested that they should contact the lab to find out what their advice was about increased lead levels.
A Yes. There are two shorter follow-ups that one would ordinarily do. One here is contacting the lab so that the concern is whether this being above the usual cut-off of 100 on this particular laboratory it is reliable, but the follow-up clinically is a quite a separate issue and really the lab are not the right people to contact on that.

Q It might depend on what happened as a result of that?
A Yes.

Q You have looked through the local hospital records of these children. Do we have any other evidence of high lead levels in any of the children at any stage?
A Oh, yes, there are several that we have commented on.

Q No, in the local hospital records, in other hospitals, not in this one?
A Oh, I see. I do not recall, I have to say.

Q If you have a history of eating carpets, is that something that is likely to provoke an investigation of the metal levels in the blood?
A Not particularly; it depends on what the carpet is.

Q But it would point in the direction of pica, would it not, as a possibility?
A Yes.

Q I am not saying that the carpets contain lead, but it shows that the child is prone to eating foreign bodies, which may lead to pica?
A Yes.

Q If you had had reported to you that he has that usual eating habit ---
A You would look for others.

Q Would you look at the blood just to make sure that is ---
A Possibly; carpets are not a source of lead ordinarily but, yes, if you find pica with one sort of substances, you obviously make inquiries as to whether there is pica on others.

Q The child’s taste may not only be for carpet?
A Quite so.

Q That is the whole problem, is it not; you may not know what it is that is actually causing the problem and we know that in the child who was readmitted to the Royal Free for surgery that that was a Christmas decoration that was eaten?
A Yes, I think so.

Q In the case in XXX which does show a follow-up, it is pointed out to the XXX physician that the lead levels were high, much higher in fact than the one we have just looked at, I think double that, and he invited the local paediatrician to re check those lead levels. That is perfectly responsible follow-up, is it not?
A Yes. I have already commented that that was appropriate and I am not critical of that being done locally rather than centrally, particularly as the child lived in XXX.

Q If we wanted to take the time, we can see from the correspondence, there is a great deal of correspondence between the local paediatrician in XXX and Professor Walker-Smith about that, and a subsequent reference by the paediatrician to the poisons unit, I think it was, at Great Ormond Street. So it carried on. It did not just simply stop with the letter?
A No, I am not critical of that at all.

Q In the case of Child 5, as you went through his case, there was a reference by Dr Berelowitz in this letter explaining his findings that the child had unusual features and that the usual chromosomal studies needed to be done.
A Yes.

Q You said that you would have expected that then be followed up if this was clinical care. As we were going through, I asked Ms Smith to point out the note in the notes of that case which said bloods 4 fragile X and chromosomes?
A Yes.

Q So you accept that that was done, on the face of it?
A Yes.

Q Again we do not see the follow-up, but that was proper clinical care to do that, given the steer that had been given by the psychiatrist?
A Yes.

Q In relation to this criticism or straw in the wind, if you like, it cuts both ways. Sometimes there is follow-up , and we can find other examples as well; sometimes there is not. We cannot draw very much positive evidence one way or another as to whether or not this bears on the issues of whether this is research or clinical care. It is rather like the outpatient clinic appointments?
A Well, not really, but I need to remind everybody that of course my expertise is not in gastroenterology; it is in neuro-developmental disorders, so that my criticisms are not on the follow-through on the gastroenterology side, which I was not an expert on and I had no particular criticism of, and I would accept that there are plenty of examples where there has been a follow-through that to a non-expert like myself seems perfectly appropriate. On the neuro-psychiatric side, although one can find the odd example where things have been followed through, like the XXX child (9) in relation to the exceptionally high lead, for the most part that is not adequately dealt with. Of course I recognise that the admission was to a gastroenterology department, but the rationale was of the co-occurrence of two disorders: one involving the gut and one involving the brain. So that my criticisms are on the brain side, if I can put it that way, not on the gut side.

Q When you are saying that this looks like research, this is not directed at the gastrointestinal side – lack of follow-up is a reasonable point to make; it is the lack of follow-up on the neuro-psychiatric or neurological side?
A Yes.

Q I was going to ask you but I do not need to because you have said so: there is evidence in one case, I think in Child 5’s case who is brought in for another barium meal and follow-through because they think that the first one shows that he might have a stricture representing Crohn’s disease and it turns out to be an anomaly. That is an indication on the gastro side that they were looking after the interests of the patient?
A Yes.

Q You make the point in cases where there is no overt reference in the referral letter to gastrointestinal problems that it obviously does bear on the gut side. You say in a number of cases there is not any reference in the notes to the fact that this child had gastrointestinal symptoms, so that may indicate that they were involved simply in research?
A Yes.

MR MILLER: This is a bit more time-consuming but I am going to ask you to look at the admission letters of all of the cases that we have here. It is only time-consuming because you have to pick up the files and put them down again. I am only going to ask you to look at the letter in the various cases. I am sorry to do this. Sir, I am not going to be going into any of the other files after this. It is just a fairly limited exercise, just so that you can see the point.

THE CHAIRMAN: Perhaps you could give us all the references so that we can get those out.

MR MILLER: It is Child 1, 55 ---
A Is this on the GP or the Royal Free records?

Q I am sticking all the way, except for Child 7 and Child 6 to the Royal Free notes. It is Child 1, Child 2, and Child 3.
A What page number do you want me to look at for Child 1?

Q Pages 55 to 57. Pages 55, 56 and 57 is a composite patient referral letter and I think the substance of the letter was on page 57. The letter which we have seen states:

“I understand that [Mr and Mrs 1] have contacted you regarding their youngest son, [Child 1], who has been diagnosed as autistic.”

The penultimate paragraph reads:

“We do not have very much correspondence regarding [Child 1], but I have photocopied any relevant information that is available.”

Following that in the Royal Free notes, in the correspondence that was sent with that, including at page 58, which is a letter from Dr Hauck, Consultant Psychiatrist (Learning Disability) which was included with that note, in the third line it states:

“It gradually emerged that [Mrs 1] is much exercised about [Child 1’s] eating; he is a choosy and slow eater and she feels he is not adequately nourished. He suffers from loose stools on most days, she tells me.”

Then she deals with the diet. Although, on the face of the referral letter, there is no reference to gut symptoms, there clearly is in the accompanying correspondence that went with it?
A Yes, though I would return to the point I made earlier that if you are referring to a gastroenterology department, ordinarily the referral letter will indicate a gastroenterological problem, at least as perceived by the referrer. As I have pointed out, there are cases where that is not mentioned in the referral letter, where the assessment by the gastroenterologist has picked up a problem. So my comment is not on the expertise of the gastroenterologist; it is that the referral here focuses on the three things basically, from my point of view: one is the autism; the other is the family history; and the third is MMR. I accept that Dr Hauck’s letter mentions gastroenterology problems; it is not actually in the referral letter itself.

Q No, but the fact is that that is what is finding its way to the Royal Free?
A Yes.

Q And I think that we were told by the general practitioner that this child was not seen very often, did not come into the general practice because he was so disruptive, and I do not think she had seen him very often, and that he was being seen in the community by other doctors. I think that is a feature of at least that case and other cases, that they were not seen very often in the general practice but were dealt with either by community paediatricians or, in this case, a psychiatrist?
A Yes.

Q In terms of where the report is, the report is to the psychiatrist rather than the GP. Child 2: this is a case which had a history, did it not, which went back before the time that Professor Walker-Smith was at the Royal Free Hospital?
A Yes, I think that is correct.

Q True it is that the original referral letter from Dr Wozencroft, who was a child psychiatrist, in 1995, did not refer to gut symptoms, abdominal symptoms, but this is in ’95 when he is at Barts.
A Yes.

Q Which clearly has nothing to do with what happened at the Royal Free in terms of any proposed study in 1996, and of course he had seen this child in 1995 and made his own appraisal of the child. There were certainly bowel symptoms present when the child was seen in 1995.
A Okay.

Q So this was a child he knew anyway from the previous year?
A Yes.

Q Just on that point, and I am not going to ask you to do it because it is the outpatient clinic note from 1995, which for the record is at page 25 in the Royal Free notes, I cannot expect you to read Professor Walker-Smith’s writing because it is all his handwritten notes, but there is reference to the fact that there were bowel symptoms there?
A Okay.

Q For Child 3, which is at page 38, there is a reference to severe constipation requiring frequent enemas and oral medication?
A Yes.

Q On the face of it, what the implication of that is to a gastroenterologist we will have to hear from Professor Booth, but, on the face of the referral letter, there are clearly bowel symptoms.
A Yes.

MR MILLER: Child 4, page 27; Child 5 at 362; and Child 6 in the GP records at 125.

THE CHAIRMAN: I request that you give us there references when you deal with each particular child.

MR MILLER: Child 4, page 27, the past paragraph on that page:

“Since 1994 [Child 4] has continued to have intermittent problems with his bowels with diarrhoea that [mother] relates to food intake; he has had a negative test for coeliac disease and has on at least 2 occasions had giardia but he has had no further investigations regarding the cause of these symptoms?”

So there is a clear reference in the referral letter to bowel symptoms.
A Yes, there is, although I do note that the child has had two attacks of giardia, which is of course an intestinal infection, which does indeed lead to bowel symptoms and that the emphasis in the letter is on MMR.

Q Yes, but he has had no further investigations regarding the cause of the symptoms. There is a reference. Your original point was not the balance of the referral but the fact that there was no reference in the referral letter to bowel symptoms.
A Which is true in some cases but not in others.

Q It is a limited expertise which we are going through just to identify in each case whether or not there is either directly or indirectly reference to bowel symptoms which would be seen as justifying an outpatient visit. You accept, I hope, that the letter, on the face of it, however it may be explained away, has a reference to continuing bowel symptoms?
A Yes.

Q On that point, over the page at 28:

“As I say, [mother] is convinced that both [Child 1’s] behaviour and his diarrhoea are triggered by his diet and she has him on something of a restrictive exclusion diet. He has not gained weight and we have been very concerned about this and [mother] feels that this is despite him being on a more normal diet. We have therefore not made any assessment as to whether his failure to gain weight might be due to an inadequate diet or possible malabsorption.”
A Yes.

Q So the combination of those two paragraphs is clearly a case, on the face of it, that is ripe for investigation.
A Yes.

Q Can I move on to Child 5. This one is a case where you may say this is your best example, or one or of your best examples, of the fact that on the face of the letter there is no reference to bowels symptoms. If you look at what Dr Shillam was writing, although there had been a discussion earlier, if turn to page 362 it starts:

“This 7¾ year old autistic child’s parents have been in contact with Dr Wakefield, and have asked me to refer him to yourself regarding your current study into association between autism and childhood bowel problems.”

A Yes.

Q Although, it does not refer to this child having symptoms, the GP is being asked to refer to that unit. He deals with the autistic features in the middle, and in the last paragraph he says:

“His parents are concerned about an association they have read in the ‘Daily Mail’ between MMR vaccine, childhood enteritis and possible brain damage.”

So you say the concentration here is on other aspects rather than the bowel, it seems?
A It would seem so.

Q Although the referral is to the gastroenterological department and, as he introduces, it is clear that the parents want the children to be seen there.
A Yes.

Q Child 6 in the GP records at page 125. A brief referral letter, but following a telephone conversation, says:

“[Child 6] is a little boy with autism syndrome who does also suffer from bowel disorder. His mother is interested in entering him into your trial and I would be grateful if you could see her for discussion.”

On the face of it, and we know from what we see subsequently, there is a reference by the referring general practitioner to bowel disorder?
A There is also a reference to the trial.

Q It is written to Professor Wakefield rather than Professor Walker Smith?
A Yes.

Q If you like, you can argue the case for the trial at the same time, but this is only a limited exercise. It is trying to look at the strength of the observation you made to the Panel, two days ago probably, that one of the features was the absence of reference in the referral letter to bowel symptoms, and that is the only point of this exercise, simply to see the strength of that and the way in which we have other criticisms you have made. Ms Smith can argue other aspects of the letters, but that is all I am asking you about at the moment?
A I do understand that, but I do need to come back to the point I made earlier that as any responsible clinician or scientist, you have to go on the overall picture, so that with none of the cases have I gone on one item of information.

Q We are going to get to Child 7 at page 89 and Child 8 Royal Free Hospital page 119.
A Child 7 is on what page?

Q Are you on Child 7, Royal Free?
A So, 7 is Royal Free or GP? I have already been reprimanded for being ahead of the game, so I need to be focused on whatever you are going to ask me about.

Q I am the Ring Master, I am supposed to be telling you. The difficulty is that the reference is being made in the two different bundles for obvious reasons, because they come from one and go to the other. I do not want to confuse everybody by having different bundles open. If you could stay behind the game for the moment. If you stay in the GP records for Child 7 at page 282. You were making the point that of course it is not just one feature that you have taken into account, you have put them all together and come to a conclusion from everything. You say that this exercise, and others in relation to other criticisms or points you have made, is simply looking at the strength of those points.
A Yes.

Q If you look at them individually, and when you look at them again you look at the overall strength as to whether or not they suggest. As I say, recognising that you can have clinical care running in parallel to research, although the research aspect has to be dealt with in an ethical way, clinical care can be running at the same time and patients may be seen for their benefit although they may provide information which may help research?
A Yes, I agree with that.

Q Child 7 GP records 282. We do not need to look at the ultimate diagnosis as far as the psychiatric diagnosis is concerned, but as far as the referral to the gastroenterological department is concerned, the general practitioner – who has already just referred the sibling, and we heard had also referred other patients, including his son – is referring to the fact that he suffers from bowel problems as well. So, on that simple point, on the face of the referral letter, there is an apparent reason for going to that department?
A I accept that.

Q Child 8, which is Royal Free page 36, again nothing on the face of the referral letter, but we know that in this case a good deal of the earlier correspondence was enclosed with that letter. The whole history was enclosed in a series of letters, which you have been through, involving the local paediatrician which clearly makes regular reference to the bowel problems which this child had, particularly loose stools. Again, rather like the one we saw before in Child 1, the referral letter may concentrate on one aspect, but the documentation which followed it clearly shows the history that this child had bowel symptoms.
A I accept that. I point out again that this is linked with an investigative programme and is linked with MMR.

Q Please do not think that I am trying to distance myself from that aspect, it is purely on the bowel symptoms because I am representing Professor Walker Smith who is the person who is fielding these particular referrals.
A I understand.

Q Child 9, the referral letter from Dr Spratt is at page 38 in the Royal Free notes. Again, there is nothing in the referral letter, although we know the circumstances in which the child came to see Professor Walker Smith, but you are aware, I think, that there had been a recommendation the previous year from Dr Cavanagh, the consultant paediatric neurologist at the Chelsea and Westminster Hospital, that the child should be referred to Professor Walker Smith. You have seen those records?
A Yes, I must have done. I do not recall the details, I am afraid.

Q Child 10, is Royal Free, page 35. The last one is child 12 at page 69 in the Royal Free bundle. Child 10, nothing in the referral letter, but we see from the referral letter that the father had heard of your work and “is keen for 10 to be assessed by you.” So you would say that that does not necessarily suggest that there are bowel problems, although undoubtedly it turned out that there were?
A Sure.

Q Finally Child 12 at page 69:

“[He] has for some time had bowel problems, but did not present to my surgery until March this year when [Mrs 12] came to discuss his soiling habit.”

On the face of the letter the bowel symptoms are referred to?
A Yes.

Q Soiling may have implications if you are dealing with autism, which they might not have if the child had straightforward bowel disease, in the fact that it is soiling rather than anything else, but that is a matter which is going to have to be teased out when the child is seen as to what may be the cause. He has had bowel problems for some time which, again, is an indication that the GP anyway was aware of those problems at the time of referral?
A Yes, that is so. In this particular case, Child 12, of course there are other things that raise concerns as to whether it is clinical care or research, so that we, I think, have commented, but certainly I have in my report, that Professor Walker Smith had made an explicit statement the child should not have a lumbar puncture. That is recorded in the notes, and that, despite that, the lumbar puncture was done. I do not know at whose request, but that is an example where a proper clinical decision of a responsible kind by the responsible consultant, Professor Walker Smith, apparently – well it was overruled we do not know by whom.

Q We have to be a little careful. It was either overruled – overruled implies that somebody else applied their mind to the decision.
A Okay, either way.

Q It may be a fair point because I think, between the ward round and when the lumbar puncture was taken, the child was seen by Dr Harvey. In terms of the timing, there is a note between the two, but I do not have
A I do not know how it happened.

Q You rightly make the point that in that case Professor Walker Smith in the ward round explicitly said, and that would presumably be for the consumption of those on the ward round, that this is a child who should not have a lumbar puncture.
A Yes.

Q I think the thought in that case was that this was Asperger’s at the beginning. Whether that diagnosis was maintained I do not know, but at the time that that admission took place it was thought it was Asperger’s which would not, in your judgment, merit a lumbar puncture?
A Yes.

Q He will explain his reasons, but, clearly, on the documents, Professor Walker Smith is saying that this child is not to have a lumbar puncture and, for whatever reason, he did?
A Yes.

Q Where does that leave us, that exercise? It shows that there is no explicit reference in the referral letter or the accompanying documents in the cases of children 5, 9 and 10, but to direct or indirect evidence, by which I mean the clip of papers that accompanied them, in the others, except in the case of Child 2, who was known to Professor Walker Smith anyway. That seems to be the position. You would say in a different context, “Yes, but I am concentrating on the other aspects for which the referral was taking place”?
A Yes.

Q As far as the bowels symptoms, it is fair to say that in the majority Professor Walker Smith was being equipped with information, at least, to see the child in the outpatient clinic?
A Yes.

Q I want to ask you, a little, but not much, because Mr Hopkins went over it in some detail yesterday, about lumbar puncture. A lumbar puncture is not, in a hospital which has all specialisms in it, the preserve of a child psychiatrist?
A No.

Q It may be that you or your team, if you had inpatients at the Maudsley, would be carrying out lumbar punctures but in most cases lumbar punctures are not done by psychiatrists, are they?
A No.

Q Dr Berelowitz said, I think in answer to questions from the Panel, that lumbar punctures are usually commissioned on the advice of paediatricians? You are nodding.
A Yes. My concern throughout these cases is not that that is an inappropriate thing for a paediatrician to do. I accept that would be something that any paediatrician would know about. My concern is a quite different one, as to whether those paediatricians responsible knew enough about regression and disintegrative disorders to take an informed decision as to whether a lumbar puncture in this case was needed.

Q We will hear that Professor Walker Smith was in fact involved in general paediatrics until he moved to the Royal Free, so from the time he trained up until the time he left in 1995?
A Yes.

Q Dr Thomson had general sessions as a paediatrician at the Royal Free so, again, they were paediatricians rather than people who used to be paediatricians. I take your point that, if you are looking at it from the point of view of regression, then they may not have had sufficient knowledge to decide whether or not it was appropriate to do it. That is your point?
A Yes, it is and on this I am relying not so much on what I know and do not know about Professor Walker Smith’s background, because I accept that he has had experience in this and, indeed, it would be very surprising if he had not, it is in relation to the letter we referred to yesterday in which the statement was made about hopeless prognosis in that, to me, that meant a lack of understanding of the kind of clinical problems which were having to be decided about in relation to lumbar puncture. It is on the specifics, it is not on the general. I do not question that paediatricians know about lumbar puncture.

Q We forget that in acute paediatrics they are regularly the first point of call to see whether or not
A I do not question that at all.

Q I think also to be fair, you said in answer either to Ms Smith or Mr Hopkins, that they are generally regarded as a safe procedure to carry out?
A Yes, they are an unpleasant procedure but they are safe in proper hands.

Q What I would like to suggest to you, and you may not agree, is the fact that if in these cases the paediatricians were getting a clear history, accurate or otherwise, of regression, and there is no doubt they were getting a history of regression in these cases – whether or not it was accurate or could be relied upon – they were getting a history in a lot of the cases, were they not?
A In some of them.

Q It was reasonable to follow that line of investigation by carrying out a lumbar puncture?
A No.

Q We have seen in the case of Child 2 the sheet of proposed or possible investigations?
A As I said already, in relation to Child 2, I do accept that a lumbar puncture was a reasonable thing to have done. Child 2 is a very unusual case.

Q My point is a very different one. There is there set out on that sheet proposed investigations for a lumbar puncture which, on the face of it, would be apt to see whether or not there was any progressive neurological problem?
A Yes.

Q A couple of points to finish up. Again it is just trying to look at it from the point of view of the gastroenterologist. I am not asking you for the detail of the treatment. Looking at the thread that we see through all of these cases, that in their hands, these children were being, in the most cases 9 out of 11, seen first of all by Professor Walker Smith and assessed from their gastroenterological point of view, admitted and investigated thoroughly and treated, I think in all most every case if not in every case, for a period of time anyway, in some cases right up to the present day?
A Yes.

Q That was usually decided, not necessarily at the time of discharge but at a follow up outpatient clinic appointment, presumably when matters were discussed?
A I do agree with that. The point I would make is that the gut problems – and you will understand that my experience of that is in relation to autism not as a gastroenterologist – the point about incontinence, ie a failure to gain bowel control, the role of PICA, the role of retention with overflow, to my mind were not given as much attention as one would expect, given that this is dealing with the co occurrence of gastroenterological symptoms, GI symptoms, and initially a disintegrative disorder and then later looked at more broadly of autism spectrum disorders.

Q Your point maybe that these are often found, these conditions are often found in autism, but my point was a slightly different one. I am concentrating on what they did or their approach – whether it was right or not, but their approach – appeared to be that they were seen, investigated and followed up in some cases for many years?
A Yes.

Q We have heard the evidence, you have read the evidence, from Dr Casson and Dr Davies, who was the histopathologist – who was dealing with all the cases, not just these twelve cases but she was the dedicated histopathologist – of the fact that all of these children who were coming in for investigation were treated in the same way to the extent that they come in on the Sunday and had their colonoscopies on the Monday, remained as inpatients and then, at the end of the week, there was a meeting in which all the cases were thrashed out by all concerned and decisions made; but not simply autistic children but all the children who were investigated. Again, on the face of it, that looks more like clinical care than research?
A So far as that is concerned.

Q As far as investigations like MRI and EEG are concerned, what would be the purpose of carrying out those investigations?
A We have discussed some of the things. Let us deal separately with EEG and the brain scan. The brain scan would be of value in relation to tuberous sclerosis, although that would not ordinarily be the way you would start, but it is certainly the way you would pick up tumours in the brain. The reason you would not start is because, as a clinician, you would first of all be concerned with skin manifestations in order to see whether that leads you down

Q That is your Wood’s lamp.
A Yes. EEG is of diagnostic value occasionally in relation to particular kinds of progressive neurological disorder but in the absence of epilepsy is not very informative.

Q It would be right to say, would it, that these were investigations that might throw up some other cause; rather like the lactate and pyruvate glucose in the lumbar puncture might show up some organic reason for the behaviour?
A Yes.

Q They are in the same sort of category, are they?
A They are in the same category.

Q The final thing is it looks from various sources, not least the footnote in The Lancet paper but also the evidence of Dr Berelowitz, that long after these 12 children were seen, children continued to be seen, investigated and treated in the gastroenterology department.
A Yes, that is what the footnote implies.

Q If you have seen Dr Berelowitz’s evidence, he was shown a document from 1999, I think, on which there was a list of patients who were due to be seen by him after that. It was not just alluding to 12 cases; it obviously went on beyond that.
A Yes.

MR MILLER: Thank you, Professor.

THE CHAIRMAN: Ms Smith, next is your re-examination. I am looking at the time, but, before we adjourn, can I just get some idea roughly how long your re-examination is going to be. I am not going to make it binding on you.

MS SMITH: Sir, as you know, we are all notoriously bad at saying exactly how long things are going to be, but I think I will probably be half an hour, although it may be a little longer.

THE CHAIRMAN: We will need to build into that going through our notes for about half an hour or so, to look at the questions we need to ask of Professor Rutter. That is helpful. Hopefully, we should, at a reasonable time, be able to see Professor Rutter.

MS SMITH: May I just ask: you are envisaging your own consideration after my re examination.

THE CHAIRMAN: Yes. It is 11 o'clock. We will adjourn now, resume at 11.20 am and start with your re-examination.

Professor Rutter, my usual warning remains. You are still under oath. Please do not discuss the case.

(The Panel adjourned for a short time)

THE CHAIRMAN: Professor Rutter, Ms Smith is now entitled to do the re-examination as you have been already asked about that particular issue. Following that, the Panel will have the opportunity to ask you a few questions. I will introduce the Panel members when we are going to that particular stage.

Re-examined by MS SMITH

Q Professor Rutter. I hope this does not involve too much mental gymnastics. Being re-examined inevitably is taking you back over areas where I want clarification so I will be hopping around a bit. Tell me if you need to time to think about what I am asking you. I want to go back, first of all, in relation to some of the questions Mr Hopkins asked you yesterday. He is representing, as you know, Professor Murch. You were asked about the situation if Dr Harvey, the neurologist involved in this project, had advised that lumbar punctures should be carried out in cases of autism. You pointed out that that was hypothetical since it was clear from the protocol that it was being put as disintegrative disorder. Nonetheless, you were asked to address that hypothesis, and I want to be clear as to what your answer was on that. If, hypothetically, Dr Harvey did say lumbar punctures should be carried out generally in cases of autism, would that discharge the treating clinicians from having these patients assessed individually by someone with the requisite expertise before carrying out that procedure?
A No, because, unless it is part of a pre-planned research study, it would have to be decided on a case-by-case basis. If Dr Harvey had had the view that ordinarily one would do a lumbar puncture with children with an autism spectrum disorder, I would be surprised. I would comment that that is completely out of keeping with practice in the UK, but I would say that, even if that were his view, it would have to be decided on a case-by-case basis if the child was part of ordinary clinical referral and care.

Q Thank you. Turning to the vexed question of Professor Gillberg: first of all, you were aware, I think it is right – indeed you and I discussed them when I was taking you through your report – of the views that Professor Gillberg had expressed in the literature prior to advising on this case.
A Certainly.

Q It has been suggested to you by Mr Hopkins that Professor Gillberg advocates lumbar puncture regardless of individual circumstances. I just wanted to look back at one of the references which I think is representative of the views he is expressing. If we look at page 252 of FTP 5, we can remind ourselves of what Table 3 is:

“Relevant laboratory analyses in all medium-low functioning and certain high-functioning cases with autism and autistic like conditions”

and if we then go on to page 253, the left-hand column, it says:

“Table 3 briefly summarizes the laboratory work-up which should be seen as essential in any young child with autism given the present day information of the biology of autistic syndromes. All the examinations listed usually have to be performed in middle-and low-functioning cases. In older cases, some of the examinations could probably be excluded, even though there can be no clear recommendation as to the whole group of post-adolescent cases needing only a more limited laboratory work-up. With respect to cerebro-spinal fluid (CSF) examinations, current practice tends to vary considerably. In the Scandinavian countries, a lumbar puncture with CSF protein electorphoresis is considered one of the basic procedures in the work-up of severe developmental disorders without a clear cause.”

He then refers to the fact that the attitude elsewhere is more conservative, and goes on:

“Several authors have documented that clear progressive encephalopathies were first suspected on the basis of results obtained at CSF analysis. It is therefore my contention that a CSF protein electrophoresis should be part of the work-up in autism in early childhood.

In high-functioning cases, some of which are now often referred to as Asperger syndrome, all of the examinations have to be considered, because of the relatively high risk that even in such cases underlying medical conditions/brain damage are common. However, if there is a clear family history of autism or Asperger syndrome in such cases, the clinical analysis might well lead up to a less extensive work-up, even though the threshold for further neurobiological investigations should be low. In particular, there is probably a need to screen Asperger syndrome/high-level autism for the occurrence of the fragile X syndrome. Also at the present stage, the empirical evidence, concerning the heritability of Asperger syndrome, is relatively weak.”

and then he goes into the reasons as to that. All those references, the fact that he says:

“All the examinations listed usually have to be performed in middle-and low-functioning cases. In older cases, some of the examinations could probably be excluded …” –

and then he refers to particular considerations in high-functioning cases – does that necessarily involve an individual assessment of the child?
A Yes. That was the point I was trying to make, that he actually advocated quite systematic and detailed assessment clinically – and I previously went through some of the issues like family history, congenital anomalies and so on – and that the section that you have read out indicates that he does not see that as simply a routine: you tick the box of clinical assessment and then you tick the box of lumbar puncture. He is saying that the threshold for using lumbar puncture should be low on the grounds that it is often informative but he then goes on, as you note, to indicate that in milder cases you may want to do it or you may not: that will depend. And he then talks about family history as being relevant. I actually disagree with what he says about family history because I do not think he quite understands how genetics works. The point is not really that but that he is also indicating that this is an individual judgment. The difference between what he is advocating and what would be the usual practice in all centres that I know about in the UK, is that his threshold is low for lumbar puncture rather than high but it is still based on a detailed clinical assessment of an individual case.

Q I am not going to take you to all the other references Mr Hopkins has gone through, but there are references elsewhere to the same proposition.
A Yes.

Q Always with words such as “lumbar puncture has to be considered”.
A Yes.

Q Even if a clinician were to follow Professor Gillberg’s line, would that require an individual assessment by someone who is able to assess the particular gradations of the behavioural disorder and the indications as to whether lumbar puncture should be performed or not?
A Yes, it would.

Q To that degree, although I go no further, you and Professor Gillberg might be said to be at one.
A Yes, that is correct.

Q Again, you have answered this – forgive me if I am labouring the point – but do you regard paediatric gastroenterologists, whether generally paediatrically trained, as we were told they were, or not, as the appropriate people to make that assessment?
A Not ordinarily. I mean, I have to add “not ordinarily” because people’s expertise varies so widely, but that would not ordinarily be part of the experience of a gastroenterologist, even with an extensive paediatric background.

Q The papers to which Mr Hopkins took you – and again I am not going to go through them all – as a general proposition emanated from departments of neurology and educational psychology. Indeed, with respect to the mitochondrial disorders from departments of genetics.
A Yes.

Q Is that what you would expect to see: these sorts of sophisticated evaluations to come from those kinds of specialist departments?
A Yes.

Q As far as the scientific protocol which was submitted to the Royal Free ethics committee and, indeed, the ethics application itself – I can take you back to it if you wish, but I know you are pretty familiar with those by now – is there any express indication that these clinicians had significant concerns about mitochondrial disorders?
A I think not. I have forgotten where in the documentation mention is made that one of the clinicians had had experience in Birmingham on it but I do not think it appears in the protocol.

Q Not in the protocol submitted to the ethics committee.
A Yes.

Q If these clinicians had undergone a balanced consideration as to the investigations they were going to undertake and they decided to undertake investigations which were, as you have told us, contrary to UK practice but might have some support from an overseas source (that is, from Professor Gillberg), have you seen any indication anywhere in any of the papers you have looked at that that balancing exercise and that decision-making process took place?
A No. That is one of the key things that made me feel that the overall picture – regardless of the fact that clinical aspects were dealt with appropriate in many instances – the overall plan, was a pre-determined one not related to the systematic assessment on the neuropsychiatric side. I make that distinction from the gastroenterology.

Q If they had decided to do lumbar punctures for clinical reasons, you have already told us that you would have expected in those circumstances to see some indications of the reasons for it in the clinical records.
A Yes.

Q If they are deciding to do lumbar punctures for clinical reasons and they are aware that they are stepping outside – if your expert evidence is accepted by the Panel – normal UK practice, would you expect to see some careful analysis as to why they were doing that?
A I think so, yes. I mean, one is never bound, as a clinician, to follow usual practice if there are very good reasons for departing from it, but you do so at the hazard, as it were, of being accused of doing something that is unacceptable. So I would accept that it is perfectly okay for clinicians to take a decision of that kind if in their view a careful and detailed analysis indicates that they want to follow that route. But certainly I would expect that to be noted in some way because it is unusual.

Q I want to turn on now, if I may, to some of the questions that Mr Miller asked you yesterday afternoon on behalf of Professor Walker-Smith. We will come on to this morning’s questions. Mr Miller has suggested to you that The Lancet children were not part of Project 172-96. The reason he gave was that nine were seen prior to the clinicians being notified of the committee’s approval, and all, he pointed out, had been referred prior to then. He particularly alluded to Child 3 and the time at which he was referred. I want to take you through this timeline of the documents, Professor Rutter, because you, as an expert, cannot possibly be expected to retain them in your head, and then I am going to ask you some questions arising out of it. Starting off with Child 3, would you turn to page 54 of the Royal Free Hospital records of that child. It is correct, as Mr Miller has said, that this child was initially referred by the GP at an earlier date. This is the letter of 4 April 1996. If you could try to bear in mind these dates or you could jot them down if you have a pen. This is April 1996, a letter to Dr Wakefield.

“Dear Andy,

There is a clear history of this child having been perfectly well …. The second day after the MMR injection there was a change in behaviour …

On examination he looks well and fit but clearly has disturbed behaviour. I have the routine bloods, etc, and I have told the mother that we would like to consider colonoscopy within the next one or two months and she has agreed. I have not yet booked for a colonoscopy until we have got the full details of the investigative protocol worked out.”

That is the first letter in relation to Child 3.

If we can then turn on to FTP1, page 193, this is June 1996, and I should make it clear that I am fully aware that the Legal Aid Board charges relate to Dr Wakefield, not Professor Walker-Smith, but bear with me. This is June 1006, a letter from the Legal Aid Board from the solicitors, and it encloses, at the second paragraph, “a copy of a draft (not entirely finished yet) of Dr Wakefield’s proposed protocol for the study”. If you turn over to 104, you see the “Proposed clinical and scientific study”, is that correct?
A Yes.

Q If we go to the back of that, page 115, we see the practical issues: “Firstly, and significantly, this I as demanding protocol both for the children…” and setting out what is intended.

“However, it is essential that we characterise as comprehensively as possible the pathogenesis of this condition – control of any underlying intestinal immunopathology may open up new therapeutic avenues for the treatment of affected children. Our ability to confirm or exclude a role of measles or measles/rubella vaccine also has major implications for public health.”

Then, setting out the details; “Referrals will be coordinated by [Professor Walker Smith, Dr Wakefield and Professor Murch ] such that they will be admitted…. on a Sunday…. 24 hour urine…. colonoscopy…. psychiatric and neurological assessment ….. outpatient follow-up……”
A Yes.

Q So that is the protocol that goes in June from the solicitors through Dr Wakefield to the Legal Aid Board. May we go on to Child 2, and if you will go to the Royal Free records for Child 2, page 162. This is a letter from Professor Walker Smith to Dr Wakefield on 24 June 1996, so some two weeks later.

“Dear Andy,

I at last saw [2]. I think he is now the most appropriate child to begin our programme. Can we discuss together the most appropriate date? I think September might suit [Mrs 2] best.”

Then it sets out various details about the colonoscopy and general anaesthetic, and then these words:

“I think she would like a copy of the protocol that we are using. I don’t know whether you think it is appropriate for you to send her that or whether I should.”

A Yes.

Q Then in the same records we have Professor Walker-Smith to the GP at page 130, dated 28 June 1996, two days later, to the GP from Professor Walker Smith:

“I duly saw [2] in the clinic. As you know I first met [Mrs 2] via Dr Andy Wakefield who is concerned with measles immunisation and possible Crohn’s disease. I think Crohn’s disease is unlikely. Dr Wakefield has the view that there may be some kind of other inflammation which may be a relevant factor in [2’s] illness and we now have a programme for investigating children who have an association with autism and a possible reaction to immunisation. I am arranging for [2] to come in for investigation at the end of August.”

A Yes.

Q Then we have the ethics committee application and Mr Miller quite rightly pointed out that the date at the end of it was a submission in September 1996, but it is also the case that it was signed off by Professor Pounder, the Head of Dr Wakefield’s department, in August 1996?
A Yes.

Q We have the observations which I am not going to take you to because you are very familiar with them, and so is everyone, in the Lancet article ultimately when 12 children were written about, indicating that ethical committee approval had been given for the investigations that were carried out on those children?
A Yes.

Q I have asked you about what you would have understood that to mean as someone reading that paper?
A Yes.

Q Then, as you know, we had a very long gap and in 2004 an investigation is instigated by Dr Horton, the Editor of the Lancet. One of the matters which is considered is this very matter relating to ethics committee approval. We have heard evidence elicited by Mr Miller that an investigation or a meeting took place between Professor Hodgson, the Dean of the Royal Free, Professor Walker-Smith and Professor Murch and they divided up responsibilities for the topics that were to be explained. We know that Professor Walker-Smith wrote a letter about the referral of the patients and how that had come about and Professor Murch wrote one about the ethics committee. I would like to take you to that, please, which is in FTP3 at 1212. before I go to it, I should have said, and I am sorry, that we were also told by Dr Horton and Professor Humphrey Hobson that the ethics committee documentation was before them when they had that meeting. At 1212, and I am not going to take you through this entire statement which we have been through before, Professor Rutter, and I know you are aware of, I am just going to remind you and the Panel of some of the observations that are made. In the second paragraph:

“The protocol for the 1998 Lancet paper was submitted on September 16, 1996, to what was then termed the Ethical Practices Sub-Committee. It was entitled ‘A new paediatric syndrome: enteritis and disintegrative disorder following measles/rubella vaccine’. It was signed by Andrew Wakefield as lead investigator. Named consultants were John Walker-Smith and myself, with signed collaborators Peter Harvey, for the department of neurology, and Mark Berelowitz, for the department of child psychiatry. The application was initiated due to findings at colonoscopy of two children…”

He refers to 1 and says that that child was not included in the study, and then you see: “…and the second child colonoscoped (on September 2, 1996)…” That is indeed, and I do not think anyone will argue with me, the date that Child 2 was colonoscoped. It goes on with the details that that colonoscopy showed. At the bottom of the paragraph it reads:

“This child was included in the study, with additional investigations performed after ethics approval was obtained.”

That is a fact which we will be re-visiting at some later stage but is not in fact correct. If we go on:

“The title of this submitted application is a point of contention, and should be clarified. Having taken initial advice from our psychiatric colleagues on the basis of referral letters, it was considered that these children demonstrated a form of autism called disintegrative disorder.”

It then goes on with the details of that. Then down to the bottom of the page:

“This application (172-96) was for permission for in-depth analysis of 25 patients, referred either by general practitioners or the vitamin B12 unit at the Chelsea and Westminster.”

It then sets out the selection criteria in application 172-96 at the bottom of the page.

“….the presence of disintegrative disorder, symptoms and signs suggestive of gastrointestinal disease, and parental request for investigation. All patients reported met these criteria.”

Then, going over on to the next page, and in fact I am not going to read it all, I just simply want you to know what is relevant to the ethics committee application. In the middle of the page, it says:

“The protocol was referred back at first submission in November, 1996, with clarifications and amendments suggested, and was approved in December, 1996. This protocol formed the basis for all children investigated in the 1998 Lancet paper, and all were investigated. We had no idea at the time of our Ethical Practices Committee application that lymphoid hyperplasia would prove so common”, et cetera.

Then, going down to the bottom of the page:

“Following the publication of the initial report, John Walker-Smith sought guidance from the Ethical Practices Committee about further investigation ...”

He then quotes the letter. Then he says:

“This was reviewed on July 22, 1998, and data collection from clinically indicated investigations was approved.”

Then at the top of the next page:

“A local review initiated by the Royal Free medical school in July, 1998” –

that is after Professor Hull raised his concerns –

“confirmed that the application had been fully considered by the ethics committee, and that assurance had been given that the investigations were clinically indicated. It was also apparent that the continuing investigation of those children had been reviewed by the ethics committee in July, 1998, and appreciated that investigation of children seen after publication had become less extensive, and usually restricted to gastroenterological testing as thought clinically appropriate.”

He then says:

“We contended then, and still contend now, that these were standard and appropriate ….. investigations..,” et cetera.

Then at the bottom of the page:

“…I can confirm that the patients presented in the Lancet study were investigated in accordance with the ethics committee approval of December, 1996, and that no attempt was made to seek retrospective approval.”

After that long introduction, Mr Miller has said to you: how can the Lancet be a paper writing up project 172-96 when all the children were referred prior to approval being notified to the clinicians? That is the question he put to you. That of course is the charge that the General Medical Council are making in relation to these clinicians. All may become clearer later when these doctors give their evidence but what I want to ask you is this, Professor Rutter. First of all, do you understand why Mr Miller is suggesting to you what he did, in the light of these documents, that the Lancet paper was not part of project 172 96?
A No, and I demurred when I was asked that. It seems to me self-evident from this documentation, which I had of course gone through previously, that it indicates that it was. It is not implied; it is stated. So that it seemed to me that the Lancet paper has to be seen in terms of the application that went to the ethics committee. It is a straightforward statement of fact and it was agreed, as it were, at that time. So, no, I do not understand quite why that claim was being made. I do understand the point that Mr Miller was making that the clinical investigations had been done beforehand but, rather than being a good reason, that seems to me a bad reason in that its approval had not yet been obtained, and that is relevant to all that follows.

Q Mr Miller has said to you: “Well, here we are, that is the danger of going by the documents”. I want to be clear with the Panel. When you expressed your expert, independent opinion, were you indeed going by the documents that you were given?
A Yes.

Q Turning on to a slightly different but related matter, it has been suggested to you that the referral and investigation of these children, the actual referral and investigation in the gastroenterology department, had nothing to do with the performance of a research project. We have been told that Dr Wakefield’s position was as a laboratory researcher.
A Yes.

Q If that was the case, I want to ask you whether you would expect to see some of the documents that I have already taken you to. First of all, would you expect to see, in normal circumstances, referrals addressed to Dr Wakefield?
A No.

Q Would you expect to see correspondence from the Royal Free Hospital arranging admission of these children or outpatient appointments copied to Dr Wakefield?
A Well, I think it would be reasonable to copy it to Dr Wakefield in view of the connection with the research, but what is a concern to me, which comes out in some of the earlier things you drew our attention to, is that the investigations, as it were, were held up until an investigative protocol had been drawn up. To me that has to mean that it is being driven by the protocol and that that is a research enterprise. I do not have any problem with information being circulated to Dr Wakefield; that would seem to be ordinary practice . What I think is potentially problematic is the extent to which it was done was driven by the research interests of Dr Wakefield.

Q In that context, would you expect to see references to Dr Wakefield’s protocol in ordinary clinical notes?
A No.

Q If these children were being clinically investigated, would you expect to see, in the circumstances of their referrals, testing for measles?
A No.

Q Mr Miller suggests that the focus from the gastroenterology department was really entirely on GI symptoms and that the disintegrative disorder diagnosis was not a matter of great interest to them and was not followed up. In those circumstances, would you expect to see investigations being ordered by Dr Wakefield giving that as the reason for their being ordered?
A No.

Q He has described the neuro-psychiatric aspects as being a very light input. May we just look back at the terms of The Lancet article, please, which is in FTP2, page 783? That is the beginning of it. We see at the beginning under “Background”.

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

Then would you turn on to 786, which is part of the discussion, the right-hand column:

“Despite consistent gastrointestinal findings, behavioural changes in these children were more heterogeneous.”

Then going into the details of the regression:

“This regression is consistent with a disintegrative psychosis (Heller's disease), which typically occurs when normally developing children show striking behaviour changes and developmental regression….”

I will not read it all out, but it goes down for the entire rest of that column:

“Disintegrative psychosis is recognised as a sequel to measles encephalitis, although in most cases no cause is every identified.”

Then it analyses that association with the measles virus and, going on to the next page half-way down the page, the bit which we have all referred to on a number of occasions relating to an association between the MMR vaccine and the syndrome described. If, indeed, the input into the neuro-psychiatric aspects was light and of peripheral interest, is that reflected in the scientific paper that came out of the analysis of these children?
A No. To the contrary; it was a key feature of the paper.

Q Now I just want to turn very briefly, and I assure you I am not going to make you all get out these records to a great degree, and look very quickly at one or two matters that Mr Miller has made in relation to them. Before I do so, Professor Rutter, you have made this point on a number of occasions but I think I should underline it. You have been asked a lot of questions about treatment, going to the clinical aspects of the actual treatment which was given, remedies that were given, and to follow up. Are those all issues which, in effect, if they are gastrointestinal really are outside your expertise?
A Yes.

Q Child 5, I do not think you need his records just to answer this short question. You were asked about chromosomal tests, and it is correct that Mr Miller prompted me because I had, as an oversight, not referred to the fact that this child’s blood apparently was tested for chromosomes. Were you able to find any results relating to that blood testing for chromosomes in Child 5’s records that you recall?
A Not that I recall, no.

Q As far as the referral circumstances are concerned, has the tour that Mr Miller has taken you on through the referral letters changed your views at all in relation to what you have described as the “research smell” of these investigations, or I think that is how Mr Miller described it but you agreed with it?
A His phrase, not mine, but I do not disagree. It has not changed my mind because Mr Miller, quite reasonably, focused on a particular aspect of the referral. As I tried to indicate, my judgment was, however, based not on one item but on many different items so that it would be the coming together, as it were, of the link with the litigation, the fact that the parents were focusing on MMR as a key issue, the fact that parents referred to either the trial or the investigative programme, and Child 12, I think, the mother was explicitly saying that she thought that we were agreeing to a research study. I may have muddled up the children but I think that is the right one.

Q It is Child 12, you are quite right.
A It is a combination of things that makes me come to that view together with the other things we have commented on, that is to say, on the neuropsychiatric side it is perfunctory and there was a sort of steam-rollering ahead on a predetermined programme which may or may not have been appropriate in relation to the GI symptoms. I am not the right person to express a view on that, but in my view it was certainly not in justifiable in terms of the neuropsychiatric side.

Q When Mr Miller was questioning you, he took you to some cases, and Child 1 was a good example, where the GP makes no reference to gastrointestinal symptoms but there is an associated letter from the child psychiatric, Dr Hall, who does refer to loose stools ---
A Yes.

Q --- in a letter which was sent with the GP letter. You said, “If you are referring to gastrointestinal department, you would normally indicate the gastrointestinal problem as perceived by the referrer”.
A Yes.

Q Could you tell us why you are putting the emphasis on that?
A Because it is the referrer who is asking for the opinion of an expert in this area and, therefore, whether the referrer is right or wrong is something that the expert will of course express a view on after having made an appropriate assessment, but the referral is made because the person making the referral thinks there is, in this case, a gastroenterological problem on which he or she wants an expert opinion and advice.

Q In that context I only want to take you to one case, which is Child 2. That is the child who was seen earlier with gastrointestinal symptoms in 1995 by Professor Walker Smith. Mr Miller took you to that letter, the point being when he is re seen the history is known to the department, but I would like to take you to the letter. That is Child 2, Royal Free records, page 178. This was the response that Professor Walker Smith made to the GP at the original 1995 referral.
A I think I must have the wrong page.

Q Page 178.
A Sorry I misheard.

“I have now reviewed [Child 2] and I think inflammatory bowel disease is extremely unlikely.”

He says at the bottom of the page, we do not need to go through the rest of it:

“I have not arranged arrange to see [Child 2] again but I should be happy to do so should the need arise.”

Then he wrote to Mum at page 165 in the same bundle, that is the 1996 referral, saying:

“It would be very helpful if I saw him again. I have had discussions with Dr Wakefield. We have a plan of investigation ...”

and arranging an outpatient appointment.

At page 162, the letter that I have already taken you to in a different context saying:

“I think that [he] is the most appropriate child to begin our programme.”

If it is being suggested, as I think it was, that the history of gastrointestinal symptoms was known, Professor Walker Smith appears to have come to a conclusion in 1995, as we see from his letter then, that there was no inflammatory bowel disease, does your point stand in relation to query why he was back again in the gastroenterology department?
A Yes, experts in gastroenterology will have to comment in a way I cannot as to whether further investigations were justified but, as you indicate in drawing our attention to these letters, Professor Walker Smith had thought it unlikely that the child had inflammatory bowel disease. We then have at the same time a reference to an investigative programme which is linked with MMR, disintegrative disorder and so on. There is reference in these letters to timing, as it were, to fit in with the beginning of the programme. Putting two and two together and making, I hope, four rather than fifty five, it seemed to me that this was an indication that this was being decided on the basis of a research programme and that, therefore, it needed to be judged as a research programme rather than as ordinary clinical care. From the original referral, that is the 1995 one, the indications are that, so far as inflammatory bowel disease is concerned, there was not a need to do further things.

Q One last very small factual point Professor Rutter, sorry to ask you to jump around again, Child 12, that is the child where Professor Walker Smith says that he should not have a lumbar puncture and then he does?
A Yes.

Q Mr Miller made reference to the child being seen by Dr Harvey. In fact this is the child where Dr Harvey does indeed see him and makes a note, do you remember, that he was fast asleep so he could not examine him. There is no reference in that note to a lumbar puncture at all, so are we still in the dark, in effect, as to who made the decision and why?
A I think we are.

MS SMITH: On that happy note, those are all the questions that I have to ask you. I will hand you over to the Panel.

THE CHAIRMAN: Professor Rutter, as I said earlier, this will now be the opportunity for the Panel members to ask you questions. You have been giving evidence for the best part of a week now, since last Thursday, and we have made copious notes so we will need to look at our notes to see if there are any points still outstanding that are not clear us to after having gone through your examination in chief, your cross examinations and re examination. That will obviously take us a little time, not too much, but a little time. It is now about 12.15 pm, so I think anything between half an hour to forty five minutes it will take us to go through our notes, which will take us to 1pm, and then we will have our lunch break. We will now resume at 2 pm, hopefully, when the Panel will be ready to put their questions to you.
A Fine.

THE CHAIRMAN: I hope that is acceptable to all of you. As I said, we will be sitting here doing our work, but we will now go in camera to look at our own papers, otherwise all strangers can withdraw.

MS SMITH: Can I reassure Professor Rutter that you will finish your questions this afternoon?

THE CHAIRMAN: I think I will be very surprised if we do not.

MS SMITH: After the last few days I think he probably has no idea how long anyone will be.

THE CHAIRMAN: In my preliminary discussion with the Panel members, I believe there are not that many Panel questions but we still need to look at our papers to be absolutely sure. I do not think it will be very long, so I think you will be released well before the end of the afternoon. Thank you again and, as I said, if strangers could withdraw and we will start our own work.


(Luncheon adjournment)


Questioned by THE PANEL

THE CHAIRMAN: Good afternoon, Professor Rutter. As I mentioned before lunch, this is now the time for the Panel members to ask you any questions. If there are any questions from any of the Panel members, then I will introduce them individually to you. Dr Webster is the medical member.

DR WEBSTER: Professor Gillberg is obviously a great enthusiast for lumbar punctures, as you are, in autistic children. He does not actually describe the circumstances under which he does it, apart from one of the papers when it is done under a general anaesthetic. When they are done, are they are normally done under sedation?
A With children who are handicapped in the way that children with autism spectrum disorder are, almost always. In a child of normal intelligence without any kind of mental problems it might be done, but it is a very uncomfortable procedure, and I would have thought, virtually always, with children like this it would require sedation and in some it might require general anaesthetic.

Q It could be quite heavy sedation in some, as you say, going on to general anaesthetic?
A Yes, indeed, so that the risks, if you like, come at least as much from the sedation or general anaesthesia as they do from the lumbar puncture as such.

Q The children in project 172-96, on the Monday morning, have a whole series of things done under sedation or general anaesthetic. It would appear it is a quite prolonged period that they are suppressed?
A I presume so, although I do not have details of the time.

Q There is just one other question I would like to ask. In notes of Child 2, the Royal Hospital Free records, there is a copy of a research consent form there regarding the enteral feeding. On the second page it says towards the bottom:

“Subjects are warned not to take part in more than one study at any time.”

Is that a standard sort of phrase which is likely to have been on the one that none of us has seen. Is that a standard phrase on research consent forms?
A It is a standard concern and it should be on the form. Certainly over the years researchers generally have become aware that it is all very well to have agreement for an individual study, but it needs to be considered in relation to the overall burden and, hence, a phrase of that kind would be quite common.

DR WEBSTER: Thank you very much.

THE CHAIRMAN: Ms Golding is the lay member.

MS GOLDING: Good afternoon. The application for the study was for a study of twenty five children and the early report quoted twelve children. Did you see any indication of another thirteen children being studied at all?
A I have not as such in relation to the protocol, but as The Lancet paper brings out, there certainly is a report of many more children being investigated. Whether they were being investigated with the same protocol, that I would not know.

Q The children who were included in this study were supposed to fit a certain criteria and the research was to test the hypothesis that the MMR vaccine and measles virus in particular was present in the bowel of autistic children?
A Yes.

Q How often would the measles virus, or would you know – would the measles virus be in the gut of an autistic child?
A I cannot really answer that at an expert level, but organisms do tend to be in a variety of tissues and, in particular, those which show pathological changes, so that if there is virus around, it might well be present in the gut. Whether it is causal in the gut is an important secondary question, but you could not actually answer that from simply it finding it there.

Q Would it have been a way forward in this study to test that hypothesis that measles virus was present before doing any other type of investigation?
A That certainly would be one way of doing it. I think that the whole issue of what the research strategy was is rather obscure in all the documents. What the issues were is clear enough, but how the researchers were to determine not just whether the virus was there but whether it was causal is left really rather vague – and you are quite right that that is a crucial element. I would not necessarily be critical as to which order it is done in but it is certainly a key feature in the research.

Q I believe this class of research was classified as non-therapeutic.
A Yes.

Q Some of the patients were prescribed therapeutic medicine.
A Yes.

Q Does that move them from being a non-therapeutic patient to a therapeutic, thereby changing the whole ethos of this research?
A That is a good question. No, not really, because I do accept that the treatments for the most part were done on the basis of clinical need, so that, as it were, is sort of separate from the research as such. At a general level, in the minds of the people doing it, doubtless there were connections made but, no, it does not make the protocol therapeutic.

Q Dr Berelowitz’s role was to confirm and characterise the disorder.
A Yes.

Q That means the disintegrative disorder.
A Yes. He interpreted his remit, I think, as providing a skilled clinical assessment, but not in terms of undertaking a systematic study to look at disintegration, as such. So that, obviously, as an experienced clinician that will have been included in what he looked at but it was not the exclusive phase, is my understanding.

Q Did he identify any of those children with disintegrative disorder?
A He identified some that involved regression. I am open to correction but I do not think he identified any of them as having a disintegrative disorder.

Q If he had not, then these children did not fit the criteria.
A No, that is quite right.

Q How rare is the disintegrative disorder?
A We do not have good figures on it but it is clearly very uncommon. In one of the papers – and I am afraid I have forgotten which one – there is an estimate that in the literature there are about 100 cases. That is not very many, when considered over the years, so it is a highly unusual disorder. Hence the response to one of the questions – and I have forgotten who from now – when I said that it would have been very difficult indeed to have accumulated 25 cases meeting those criteria.

Q That would have been my next question.
A Sorry.

Q That is fine, I will cross that off. In terms of the transfer factor, would it be acceptable to treat a patient with an experimental drug which had not had a safety verification yet, which I believe transfer factor had not.
A Yes, I think that would be acceptable, in the sense that if one is dealing with an innovative treatment it will rarely have been subject to, as it were, official acceptance of safety. One certainly would expect that it should have had sufficient study so that there is an appreciation that it is safe, but that is a little bit different from, as it were, it being approved.

Q In FTP 2, page 680, it says that one child was started “on an approved compassionate basis”.
A Yes.

Q I do not know if you were able to work out who approved it.
A I am not quite sure what “approved” means in that connotation. I took it to mean simply that the responsible consultant had agreed that this was a reasonable thing to do. In other words, it was approved at a clinical level rather than by any external body. That was my reading of that.

Q Going back to the original study, there were no controls to this.
A No.

Q Is that important at all?
A Yes, it is. From a scientific point of view, it certainly is important. It depends how one views it. If one is viewing this as an exploratory study but nevertheless a piece of research, exploratory research, it would not be unreasonable to do that without a control group in the first instance, but obviously the scientific conclusions are hugely dependent on having some kind of systematic comparison, so that a control group would definitely be required as the next step.

Q It appears to me that most of the children were already diagnosed with something related to autism.
A Yes.

Q Once that diagnosis has been made, would a child need more in-depth investigation?
A The responsible consultants made the point that in their view the degree of investigation fell short of what they regarded as optimal. The degree of investigation varied considerably across the cases. In some, it obviously had been thorough, thoughtful and one really would not want any more. In others, it is more limited, and the question then comes down to whether it should have been more extensive. The point was made most forcefully in relation to the gastroenterology, and I really cannot comment on that. So far as the autism is concerned, I think the way I would put it is like this: in terms of what is ordinarily clinically expected I think most of the cases had had a reasonable investigation. I would not wish to put it more strongly than that, so I say “reasonable and not necessarily fully optimal”. But, if you are asking the question in relation to not to clinical care and the usual clinical concern but research, then one has to give a different sort of answer, which is that we know that autism spectrum disorders are likely to involve some kind of non-genetic causal agent, and that, therefore, a piece of research to investigate that possibility as a research procedure rather than routine clinical care would certainly be a perfectly reasonable thing to do.

Q Do you feel that the ethics committee were as rigorous as they could have been in looking at this application – so that we possibly would not be here?
A That is a very difficult question to answer. It is an entirely pertinent question. I think that they had to be guided by the information that was given to them, in the same way as we have to be guided by the information made available to us – except that they did not have 40 ring-binders. Clearly, concerns were raised – I think especially by a lay member of the ethics committee – as to whether this was really okay, and hence my earlier statement, which may have been technically incorrect, that there had been repeated concerns. There certainly had been concerns within the Committee, as we know from what Dr Pegg said. How far that had been transmitted to the investigators, I am not sure. They were presented with something which was put in terms of routine clinical investigation, in which the only request that came to them was “additional specimens to be used for research”. My reading of the way it went is that they were not quite sure about that and hence the further request to clarify on that. Given, however, the clear, unequivocal statement from a senior consultant that this was routine clinical care, I really do not think they had the power, responsibility or remit to go beyond that.

MS GOLDING: Thank you.

THE CHAIRMAN: I have three or four questions, Professor Rutter. First of all, I think you said in the beginning of your evidence that you were personally involved in assessing two children for the litigation purposes.
A Yes, that is correct.

Q For the MMR litigation purposes on behalf of the company.
A That is correct – well, not on behalf of the company. I agreed to be an expert in which I was called by the company. That is not quite the same thing, in that it was an independent expert opinion that I agreed to give. But, yes, that is true.

Q You did not actually look at any of the records on the patients.
A Not in relation to this. I had looked at records and, indeed, had seen the children. The children we are referring to are Child 5 and Child 2. This is, of course, concerned with ethics issues; it is not concerned with the science. The previous one was entirely concerned with the science and not at all with the ethics. But, in order that I be able to separate the two, I got my personal assistant to look at the records to check that my memory is correct, that these were the two children. She confirmed that they were and I said, “I do not want to know any more”. I did not look at the notes and I do not remember what I said.

Q Thank you. That is what I was going to ask you. I hope that it did not cause any conflict of interest.
A No.

Q That is one of the main issues we are investigating here.
A Sure.

Q My colleague Ms Golding has asked you a question about the ethics committee and whether the committee had been rigorous enough to look into the details. I note the answer that you have just given. I am just taking that a step forward. When the title of this paper was changed and that further information was submitted to the local research ethics committee – not informing them that the title had changed, but the title was actually given quite clearly at the top as a different title – do you think somebody should have noticed in the ethics committee that this is now a changed title and perhaps asked some questions?
A Not really. Obviously in an ideal world, that would have been desirable, but given the number of applications that had to be dealt with – and Dr Pegg has outlined the numbers he and his committee had to deal with (which are very similar to the numbers I am used to in the ethics committee with which I have been concerned) – if there was no highlighting, then I think you would take it that it was the same title as you had before. The responsibility definitely was on the investigators to highlight that because it was a significant change. I do not really blame the ethics committee for not noticing that. Clearly, as I say, it would have been better if they had, but I doubt that in most ethics committees they would have thought of that – because you assume, if people do not tell you that the title is different, that it is the same because it looks more or less the same.

Q I am specifically asking you this question not only as an expert but also in your extensive experience of sitting on the local research ethics committee: how is that information filed? Is that information filed with the title, with the project number, with the name of the people it is being submitted from? I expect it may differ from place to place. Somehow or the other, not noticing now, it could have been a totally different research paper and not just a change of the title.
A That is a very good question. I think that one has to look at it in two different ways. Nowadays I think that ethics committees would look at it systematically and, when a request comes through, the key administrator as well as the chairman would look to make sure. In 1996 I doubt that would have been the case. How would it be filed? In the first instance, it is filed by a number – at least in the ethics committee with which I am familiar and the others that I know a little bit about – so that you have: “Application 1996-” and then whatever the number given is and the investigator’s name. You would not ordinarily have the name of the investigation on that. The name is implicit in the number that is attached, plus the name of the investigator. You might well ask: “Is that a safe procedure, if the name gets subtly changed?” and the answer is “It is not a safe procedure” but I think we are much more aware of that now than we were in 1996.

Q Thank you. Obviously we are concerned about the 1996 period rather than the current situation.
A Certainly.

Q Thank you. You mentioned to Ms Smith, probably on Friday of last week or maybe Monday morning, that you found it impossible to ascertain who was taking what decision, and that was in relation to Dr Wakefield’s involvement.
A Yes.

Q In the hospital setting. I think you said that he was involved in the clinical work as far as you could see.
A Yes.

Q Can I ask you the basis for that impression that you gained?
A First, let me echo your words in saying it is an impression and that I did indeed find it extremely difficult to sort out. It comes from several facts. One is that there are requests for investigations that are signed by Dr Wakefield, and therefore one has to assume that he was taking responsibility for that. It is an assumption but he was a senior investigator, not a junior research worker. So I would view it a little bit differently if one is simply talking about someone in a junior position in which the answer might be that simply the junior has been asked to do something. I have forgotten exactly what his title was at that time but clearly he was not a junior in that sense. So that would be one thing.

The second is that the protocol was laid down in relation to his particular research interests, shared to some extent by the other people, but it is that combination that makes me concerned that he was taking clinical decisions. There are various things perhaps of lesser importance but all point in the same direction. For example, attention in one question to me was related to the fact that he signed the vaccine form; that is to say the form that came from the LAB in relation to possible vaccine damage, which is asking for clinical information and he filled it in. Of course it does not have to be filled in by any particular sort of person but the expectation is that it is a clinical matter and that it would be filled in by the person who is clinically responsible. I agree that is implicit rather than explicit but it is the combination of those things that made me draw that conclusion.

Q Was that involved because of his work at the Royal Free, signing that particular form for LAB?
A Well, it was in relation to a child seen by him at the Royal Free. He would have no information other than, as far as I know, through the assessment at the Royal Free. It is possible, I suppose, that he had information that I do not know anything about, but in the records I have seen it would have been restricted to that.

Q You said “signing the form”. What about if you sign the form on behalf of somebody else?
A Again, my answer would be: if it was a junior person, I could understand how that might well be the case and one would not wish to read too much into it. So that, for example, with Dr Casson, who was a registrar at the time, I definitely would not assume that “he signed the forms” meant that he as an individual had decided something was needed. He was working entirely appropriately for a team headed by somebody else, but that is not the case with Dr Wakefield.

Q We have come across this in more than one child. Would you open the Royal Free Hospital records for Child 4 at page 67? For example, on this one he has signed it but it mentions “Request source consultant/GP Dr Harvey Speciality Neurology”.
A Yes.

Q I am trying to put two and two together. Does this actually mean that this signature is going as an independent signature from a researcher or is the signature there on behalf of Dr Harvey’s department and he is a neurologist?
A It is a perfectly pertinent question and of course it is very difficult What it says here is that this is down as the request source. I would have to look back in the records as to whether Dr Harvey made a specific request for this investigation, but, as far as I can recall, he rarely did that. That is to say, he had played a role in the development of the research protocol as applied to all of these cases, but he undertook the most perfunctory of assessments and those were rarely accompanied by a request for any particular investigation. Do I know for sure that Dr Wakefield was not asked by Dr Harvey to do this? No, I cannot possibly know that. I am going primarily on Dr Wakefield’s seniority.

Q Can I ask the next question and that relates to page 58? I know that we are going to have an immunologist to deal with those kinds of issues but if you can tell me, I will be very grateful. If not, it does not really matter because we will have a further opportunity. That mentions antibodies: measles virus, IgM and IgG. What is the difference between the two different antibodies, because one is negative and IgG is positive?
A I would rather leave that to the virology expert.

Q You do not need to open this but it is about Child 8. I think you actually said that there was very little regression to the extent that I think the child had lost only about two to three words?
A Yes.

Q That is a very small amount of speech to be lost and therefore that was probably not significant to the issue that we are looking at. What about if the child only had very little speech? What we do not know is how much speech the child had at that stage. If the child only has two to three words, would that statement still apply in the same way?
A Yes, it would in that the research instruments, as well as the classifications, vary. Let me stick with the research instruments for a moment. They usually require at least four to five words used regularly on a daily basis, so that if you have only got one or two, really you have got so little that there is really nothing to go on and at a time when children are acquiring speech, one or two or words, they are here today and gone tomorrow, or they may be. It is not of course that there cannot be a clinical reality for children having almost no language and losing that tiny little bit that they have. The problem is: how can you tell whether that is so? That is why the criteria have been put in the way that they have. As you quite rightly imply, it is not that you cannot have that; it is just that in practice it would be very difficult to know whether that was real.

Q That is very helpful. My last question is about the clinical research papers that Mr Hopkins took you through on behalf of Professor Murch. Can I ask you about the quality of the papers that were there. First of all, those journals that were mentioned, were they peer-reviewed journals?
A I do not know in respect of all of them. Some of them were certainly. They are a mixed bag. The papers varied in how good they were. The empirical studies on the whole were rather poor. The review papers were rather better.

Q That is why I am asking you. There are some peer-reviewed papers in journals which are normally peer-reviewed?
A Yes.

Q Under normal circumstances, how does the research that is carried out in Scandinavian countries compare with the British system? I know there may be some kind of bias in this because I think we are all working within the British system, but trying to be as objective as we can?
A That is a very relevant question. I have to give a slightly roundabout answer. If you are asking at a general level “Are standards in Scandinavia of a comparable level or nearly comparable level to those in the UK?”, I would say yes. There are many distinguished scientists in Scandinavia and they have a high reputation. To give one concrete example within the area relevant to this group of children, the main work publishing Rett’s syndrome, which is one of the disintegrative disorders, was carried out by Hagberg in Sweden. He was and is a world authority. If one asks it more narrowly in terms of child psychiatry, one would have to say that the standards are pretty mixed. There are some very good people but the standards would not be so uniformly high. I would not pick on it as a part of the world that one would say, “Oh, well, if it comes from there, it is not worth seeing” because some very good research comes from there. It is mixed.

Q Have you ever shared a platform together with Professor Gillberg in a medical conference?
A Oh, yes. I have done a collaborative study with him. That is the one I mentioned where in a blind assessment, and this was looking at urinary peptides, his own findings could not be replicated, but I have been on platforms with him several times.

Q Have you had the opportunity to discuss this particular issue with him about the use of lumbar punctures in disintegrative disorders?
A Yes, you will see in his papers, although he does not refer to it, that he is well aware of the differences and he is well aware that UK practice is different.

Q It is more conservative on this particular issue?
A Yes.

THE CHAIRMAN: Thank you very much indeed, Professor Rutter. I do not have any further questions. Can I thank you for being very clear in your answers.

Further re-examined by MS SMITH

Q There is just one matter, Professor Rutter, relating to the investigation form signed by Dr Wakefield. The Chairman has asked you in particular in relation to Child 4. If it were the case that Dr Harvey had had some input into the request for the EEG, would you expect to see some record that he had seen the child in that case?
A Yes, I would.

MS SMITH: I think there is no argument but that Child 4 is one of the cases where Dr Harvey had no involvement. If we can look, just as an example, at Child 12 ---

MR COONAN: With great respect, we do not know as a fact that Dr Harvey had no involvement. There may be no record. The next point does not follow.

MS SMITH: I think the question that I put to Professor Rutter was: would you expect to see some indication of involvement if there had been one? Professor Rutter said that he would have expected to see that. The point that I was making was that we cannot see any suggestion of involvement. Child 12, please, Professor Rutter, the Royal Free Hospital records, page 131. We see in that request, again signed by Dr Wakefield, the request source “Consultant/GP” is given as “Walker-Smith Harvey”. Is that correct?
A Yes, it is.

Q Is it possible to draw any conclusions as to whether they played an active part or not?
A You really cannot tell.

THE CHAIRMAN: Are there any more questions? There are no more questions. Professor Rutter, can I thank you on behalf of the Panel for giving us the benefit of your evidence most of this week. Thank you again. You are now released.

(The witness withdrew)

MS SMITH: Sir, as far as the timing from now on is concerned, there has been a slight change and I wonder if I can just deal with that with you? Can I preface this by saying that this is not intended in any way to be critical because I am aware that the expert involved has had a period of illness, but the situation which I was concerned about has arisen in that an expert report and expert evidence was served on us last night. I should say “one copy of the expert’s report” and this is it. It has to be photocopied and it then has to be sent of course to our expert, Professor Booth, who is the next anticipated witness. Then today we were given the supporting literature, this time more than one copy, and that also has to be sent to him.

He, as you know, was anticipated to start on Friday. It is necessary obviously for him, and indeed for us but principally for him, to see what the defence expert has said and also to discuss it with us if it is appropriate for him to do so. If he is to start on Friday, that becomes impossible. He has heavy commitments tomorrow morning and his weekend, unfortunately, although he would normally be willing to sacrifice it, is taken up with an unbreakable family engagement. In those circumstances, he has asked us whether he could have Friday in order to study the defence reports that have now been served. He has made arrangements in relation to his outpatient list at the end of the time that he was giving his evidence to give himself an extra day then, if that course should be taken.

It is our conclusion that, subject to any views the Panel may have that, in the circumstances, obviously he is an extremely important witness – this is a defence expert’s report served by Professor Walker Smith, so it is principally involved with all the clinical aspects of colonoscopies – it is very important that he should be given time to digest it.

I think I can confidently say that you will now appreciate just how dense some of this expert evidence is and how many files one has to refer to, and the analysis of dates of admissions and times and all these things. These all have to be looked at by Professor Booth before he gives his evidence.

What I anticipate doing, subject to any views anyone else may have, is beginning Professor Booth’s evidence next Monday. I would ask that we start a little later so that I have the opportunity to speak to him on Monday morning once he has looked at these papers. If I could suggest, say, 10 am instead of the usual 9.30 am. I have carefully canvassed this with my learned friends and we are all of the view that there will still be no difficulty in concluding his evidence in the time that is left to us because, as I say, he has added another day on the other end and, as you know, we only have one very short expert after him who is scheduled for the last Friday of our sitting time.

I hope you will feel that it is appropriate now to adjourn now until Monday morning and that you may find it useful in any event to digest all you have heard from Professor Rutter before you go all over similar matters with another witness.

THE CHAIRMAN: I am sure that there would be plenty of reading to do because, as we have been talking about, Professor Rutter has been giving evidence for about a week now. Obviously there will be a lot of reading which will need to be done and, if the Panel can get some of this done, I am sure they would appreciate it as well. I wonder whether there are any views from Mr Coonan.

MR COONAN: It sounds very sensible to me.


MR MILLER: May I put in a plea of mitigation. In fairness to Professor Walker Smith, my expert’s main report was served last week. Ms Smith’s rather theatrical gesture with the lever arch file disguises the fact that nine-tenths of that file represents chronologies drawn from the notes in the correspondence and, in fact, the individual reports only run to between two and five pages per patient, so it is not a huge amount. The final point is that we still have eight days available for Professor Booth and I would be surprised if we could not get through Professor Booth in eight days. If we do not get through him in that time, I do not think I will be the person responsible for it.


MR HOPKINS: No observations.

THE CHAIRMAN: Legal Assessor?

THE LEGAL ASSESSOR: Nothing to say.

THE CHAIRMAN: That is what I expected. We will now adjourn for Thursday and Friday. I think we will be able to spend some of that time going through Professor Rutter’s evidence and the transcripts relating to them and our own notes. We will now adjourn and resume at 10 o’clock on Monday. It is your expert and I am sure that is the right way to do it.

(The Panel adjourned until 10am on Monday 8 October 2007)

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