GENERAL MEDICAL COUNCIL
FITNESS TO PRACTISE PANEL (MISCONDUCT)
Thursday 11 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)
A P P E A R A N C E S
MS SALLY SMITH QC and MR CHRIS MELLOR and MR OWAIN THOMAS of counsel, instructed by Messrs Field Fisher Waterhouse, solicitors, appeared on behalf of the General Medical Council.
MR KIERAN COONAN QC and MR NEIL SHELDON of counsel, instructed by Messrs RadcliffesLeBrasseur, Solicitors, appeared on behalf of Dr Wakefield, who was present.
MR STEPHEN MILLER QC and MS ANDREA LINDSAY-STRUGO of counsel, instructed by Messrs Eastwoods, Solicitors, appeared on behalf of Professor Walker-Smith, who was present.
MR ADRIAN HOPKINS QC and MR RICHARD PARTRIDGE of counsel, instructed by Messrs Berrymans, Solicitors, appeared on behalf of Professor Murch, who was present.
I N D E X
PROFESSOR IAN WESTERBY BOOTH, continued
Examined by MS SMITH, continued 1
THE CHAIRMAN: Good morning, Professor Booth.
THE WITNESS: Good morning, sir.
THE CHAIRMAN: And good morning everyone. Ms Smith, I think you were in the middle of examination in chief.
MS SMITH: Yes, I am now going to turn to Child 12, so can I invite the Panel to get out the GP records and the Royal Free records for that child.
PROFESSOR IAN WESTERBY BOOTH, continued
Examined by MS SMITH, continued
Q Professor Booth, turning first of all to the circumstances of the referral, at the time you reported the referral route was not entirely clear from the notes, but we have now heard from Mrs 12, as you know, and just to remind you, she said the process was that she met the mother of Child 6 and Child 7 at a mother and toddler group who told her about a possible link between the sort of problems that she had with her child and the MMR, and in that context gave her Dr Wakefield’s name. Just to remind you and the Panel, we know that Mrs 12 in fact obtained a legal aid certificate for her son in the MMR litigation in October 1996, but prior to that she contacted Dr Wakefield directly herself and there was a phone call and a letter between them and then the first document that you had access to was Dr Wakefield’s response to that phone call and letter. It is in the GP records at page 126. It is dated 9 July 1996, from Dr Wakefield to Mrs 12:
“Thank you for your letter regarding your son. We have recently taken a profound interest in this subject, particularly in view of the link between bowel problems and Asperger’s … I would greatly appreciate if you would mind calling me at the Royal Free before 3 August, and in addition I would like you to seek a referral from your GP to Professor John Walker-Smith … It will be necessary for me to discuss the nature of the referral with your GP and I would be grateful if you could let me have his/her name, telephone number. Also could you please let me have your telephone number so that I can speak to you directly on the subject.”
After that, we know that Dr Wakefield did indeed have a telephone conversation with Dr Stuart, the GP, and there is a record of that in the GP records at page 11. if you go just over halfway down the page you will see an entry for 20 July 1996:
“Call from Dr Wakefield – needs colonoscopy, B12 absorption tests. History of measles vaccination reaction.”
That was followed by a referral letter to Dr Wakefield from the general practitioner and that is at page 124. You will see it is Professor Walker-Smith’s name and address at the top but for the attention of Dr Wakefield and the letter is addressed to him:
“Thank you for seeing [child 12] who we have discussed on the phone recently. [Child 12] initially presented at his eighteen month check with delay in talking and communication skills. He was seen locally at the Speech Therapy department and has been under the care of our local community paediatrician …”
He then goes into all his behavioural difficulties:
“He had chicken pox in January 1992 and his routine MMR vaccine in March 1992. He has for some time had bowel problems, but did not present to my surgery until March this year when [Mrs 12] came along to discuss his soiling habit.
On examination at that time his abdomen was normal with an empty rectum.”
Then it says that he has seen a local consultant psychiatrist who thought he might have Asperger’s:
“I look forward to hearing your opinion regarding [Child 12]’s further investigation and outlook.”
So, looking at that history of how the referral came to be made, is that in your experience the normal way for a clinical referral to be made to a tertiary centre?
A No, it would be exceptional.
Q As far as its exceptional qualities are concerned, what in particular is unusual about it?
A I do not recall ever contacting a general practitioner. I am not aware if any of my colleagues have ever contacted a general practitioner about a child with whom they have had no contact saying, “would you please refer”. It is also unusual for a non-clinician to be involved in clinical referrals, and it is also very odd that Dr Wakefield (or indeed anybody) would know that the patient needed a colonoscopy before having seen the patient.
Q If we can then pick up the chronology a little further: Professor Walker-Smith then writes to the general practitioner and arranges for an outpatient appointment to be sent; then we have the outpatient consultation at page 12. I think there is probably dispute that that is Professor Walker-Smith’s handwriting although we see at the top the stamp for the consultant was Dr Murch, and doing the best I can with it, we see the second paragraph deals with his developmental problems. It says:
“At 18 months his development suddenly slowed …”
Then it refers to speech and following that it sets out a possible diagnosis of attention deficit disorder from a Dr Healy and then at five and a half years he was thought to be on the autistic spectrum. There is a reference to him seeing a professor somewhere I cannot read and “? Asperger’s syndrome or hyperkinetic disorder” and going on to the gastrointestinal symptoms:
“appeared to be toilet trained at three years. Soils. Not had diarrhoea. Has variable abdominal pain”
and there is something I cannot read, can you help?
A I think it says occasionally cries but I am not absolutely certain, and “stops him eating.”
MR MILLER: “Occurring every week.”
MS SMITH: Mr Miller says it is “occurring every week”, I am not sure.
MR MILLER: It says, “has variable abdominal pain. Occurs every week. Stops him eating.”
MS SMITH: Thank you. (To the witness): “Mother had not associated vaccination with this problem until met a parents support group.” Then we see in the column of the next page, page 13, “had measles diagnosed GP at 2 years” and the details of his MMR vaccination and the fact that he had a rash thereafter. The examination that Professor Walker-Smith did appears to have been normal in every respect, including examination of the abdomen, and we then see a plan for blood tests with ESR and C-reactive protein to be tested. Before I ask you any questions about those decisions perhaps I can take you on to the letter that Professor Walker-Smith then wrote to the general practitioner, which is in the Royal Free records at page 67 saying:
“Thank you so much for referring [child 12], certainly he seems to fit the spectrum of autism. I am interested that he in fact does not have very significant gastrointestinal symptoms although as you say he has had some soiling. I note that you found his rectum was empty. When I examined him today he certainly had no evidence of faecal loading. He is gaining weight and growing satisfactorily. Some of the previous children I have had referred to me with autism have had clear cut gastrointestinal symptoms with quite severe abdominal pain and intermittent bleeding and we have gone ahead with our programme of colonoscopy and intensive investigation. However, in [child 12]’s case there is relatively minor gastrointestinal symptoms, I felt it right to perform a full blood count ESR, CRP and I will discuss further with [Mrs 12] concerning the need for intensive further investigation and if the parents wish us to proceed we could certainly arrange this. For the moment I have told [Mrs 12] to be in touch about the results of the blood tests and I have not given another outpatient appointment.”
Given what you have seen of the records would you in fact concur with that assessment, that the gastrointestinal symptoms were minor?
A Yes, I would, yes.
Q As far as soiling is concerned in a child with a severe behavioural disorder, what would be your views generally as to the significance of that symptom?
A It may, as I think went through various people’s minds when evaluating this patient, be a symptom of constipation with overflow and that at this point was not confirmed on clinical examination. The other issue that children with major behavioural disturbances often soil in the absence of constipation with overflow, just as a result of not having any bowel habit.
Q Would you have agreed that it was appropriate for inflammatory markers to be assessed and screening tests in those circumstances?
A Yes. I might have done some other non-invasive investigations as well but I think it would probably have included those investigations listed here.
Q We then see that Professor Walker-Smith wrote to Dr Wakefield, and that letter is at page, dated 21 October 1996:
It is interesting to see this child who really has the features of autism but rather minimal gastrointestinal symptoms. I did not feel it right in fact to proceed with our intensive programme at the moment until we have had ethical committee approval and it is clear that the parents wish us to proceed.”
If Professor Walker-Smith was envisaging clinical investigations, is there any reason that you can understand why he would have been concerned to obtain research ethics committee approval?
A No, they would seem to be directly contradictory concepts.
Q What is your view as to any significance in relation to that sequence of letters, the letter to the GP and the letter to Dr Wakefield with regard to whether these were in fact research or clinical investigations?
A I think there are a number of pointers here, particularly the reference to not wishing to proceed with intensive investigations before getting ethical committee approval, that indicates that this patient was being considered for investigation as part of a research study.
Q If it were to be suggested that he needed the investigations which he had for clinical reasons would you be persuaded by that?
A I have not found in this patient’s symptoms a reason for intensive invasive investigations. It would certainly be appropriate to investigate is gastrointestinal symptoms but not in the way that is being subsequently suggested.
Q If those investigations were indeed thought to be clinical indicated by the clinician, would there ever be any need to concern himself with research ethics committee approval?
Q Following that outpatient appointment, in fact child 12’s mother wrote to Professor Walker-Smith. Although it was written on the 20th it was not in fact received under 25 October, so after the correspondence we have just looked at. It is on page 68:
“Dear Professor Walker-Smith,
I am writing following [child 12]’s visit to the Royal Free Hospital last Friday 18 October 1996. My husband and I have thought long and hard about this situation since the appointment. We have also reread Dr Wakefield’s proposed clinical and scientific study notes.
We do feel that [child 12] does have a problem in that most children his age do not soil themselves a number of times a day. As well as being pale in colour and foul smelling (as are his motions in general), this soiling is always very loose which might explain why he is not always aware that he has done anything. Although I would not say it was diarrhoea exactly.
Obviously I do not wish to put my son through any procedures unnecessary but there must be a reason why he has these problems.
Also, as I mentioned to you at our meeting, [Child 12] is not growing or putting on weight like my other two children.
I keenly await the results of the blood tests and if you feel they warrant further investigations my husband and I are happy for him to be referred on to Dr Wakefield’s study project. As you pointed out, it might not help [Child 12], but if not hopefully it will be of benefit to others. There is also the chance that [Child 12] has a problem that can be detected and helped.”
It has been Mrs 12’s evidence that something along the lines of what she said in the last paragraph of that letter were indeed said to her by Professor Walker-Smith. As far as this suggestion, that the investigations might not help [Child 12] but could hopefully be of benefit to others, Professor Booth, is that the language of clinical or research medicine?
A That is very much the language of research medicine.
Q If you were seeing a child in clinic for an ordinary clinical investigation, would you ever discuss with the parents whether that investigation might help other children?
A No, not as part of an ordinary clinical consultation.
Q If it were a clinical admission would you expect the parent to be provided with clinical and scientific study notes as to the science behind any investigations that were being carried out?
A No. You may well provide them with some information about the investigations and, if you have a reasonably secure clinical diagnosis, you might provide them with some information about what you think might be wrong, or point them in the direction of information. But clinical and scientific study notes would not be provided.
Q We then come to the results of the blood tests that Professor Walker-Smith had undertaken at the outpatients appointment. Can we look at those? They are at page 70 and page 86. Can you comment on what they show?
A On page 70 those indices that are of relevant here would be the haemoglobin, which is normal; the platelet count is not high; the white count is normal and then, on ---
Q Page 86.
A Page 86 or, indeed, I think it is on 70 as well, at the bottom.
Q I am sorry.
A C-reactive protein is 6, with a normal range of 0–5.
Q So that is elevated by 1 unit?
A Yes, it is.
Q Following getting those results, Professor Walker-Smith wrote to the mother. We will look at what he said. Then I will ask you for your comment on those blood results. Can we go to page 38 of the Royal Free records. This is the letter he wrote to Mum on 25 November 1996.
“Dear [Mrs 12]
Many thanks for your letter of 20 October. I have now got back the blood tests. One was slightly abnormal. As I see that you are keen for us to proceed with investigation I think it would be appropriate for us to arrange for [Child 12] to come in for colonoscopy. I explained in the outpatients what this involved. Basically he is sedated and the colonoscope is passed through the lower bowel and pieces of tissue are taken. The children are usually admitted for the course of a week and various other aspects of the protocol are undertaken. If you would like us to proceed with this, please let my secretary know and we will arrange a date for [Child 12] to come in in the new year.”
The mother wrote back to that on the previous page, page 37, on 28 November 1996.
“Dear Professor Walker-Smith,
Thank you for your letter dated 25 November 1996.
I would like to confirm my agreement to the investigations going ahead.
Would it be possible for you to let me know what the slight abnormality was with the blood test and what the implications are? …
I look forward to hearing from you soon with an admission date…”.
And on page 35, Professor Walker-Smith responded to that:
“Dear [Mrs 12]
I apologise for the delay … The slight abnormality that you referred to in your letter was that one of the markers of inflammation was just slightly above the normal range, it just means that we should go ahead. I understand that [Child 12] is coming in in the New Year to have a colonoscopy.”
As far as that slightly elevated blood test was concerned, Professor Booth, what is your view? If it is the case that Professor Walker-Smith was using that as the reason for saying that it was now all right to go ahead, what is your view on that?
A I think clinically Professor Walker-Smith had been unimpressed with the severity of this patient’s symptoms and the overall clinical picture and initially was not convinced that invasive investigation was needed. He has got back one of several inflammatory markers which is raised to the smallest possible degree. My view is that that would not be a reason for proceeding with the next step, with a colonoscopy, without doing some other investigations.
Q You have said “to the smallest possible degree”. The raising by one unit – what does that mean in clinical terms? If you had a child coming in, and you had that result – just an ordinary child with an ordinary clinical admission – would that change your views as to management?
A No, I do not think it would. No.
Q With that background and bearing in mind the presenting symptoms as well as that blood test result, do you think there was any clinical indication for an admission for a colonoscopy?
A Not for a colonoscopy, no.
Q In the surrounding circumstances of the correspondence, what is your view as to whether this admission was in fact arranged for clinical or research reasons?
A I think there are a number of indicators that this was arranged for research reasons.
Q In particular?
A References to the study protocol, receipt by the parent of information about a scientific study and the absence of a convincing clinical indication for carrying out a colonoscopy.
Q The child was admitted. I will not take you to it, but it is in the print-out for the Royal Free Hospital records at page 3 which indicates that was an admission under Professor Walker-Smith. We see on page 71 the endoscopy clerking note. The reason for the procedure being given is “Autistic features – Soiling (Pale stools/occasional abdominal pain)” and then there is reference to pain in the knee. There was a consent form. Again, I will not take you to them but for the Panel’s benefit at page 76 and 77 there are consent forms in the standard form for research biopsies, and for colonoscopy with biopsies in the form that you have told us were standard for a clinical admission. Turning, then, to the clinical notes at page 19, please. We see:
“Admitted for investigations of Autism & Bowel problems
Then, going down to the bottom of the page, the gastrointestinal symptoms:
“Clean & dry by age 3 years
Then started soiling some time later ? when
Now soils up to x8/day
Doesn’t realise he needs to pen his bowels and doesn’t realise he has soiled
Abdominal pain – about once a week
Sometimes wakes him at night
Sometimes vomits with pain
Often has anorexia with pain”
Then, if we go on to the next page we see the plan:
3. Barium meal and follow through
5. Lumbar puncture”
Do they accord with the plans of investigations which are set out in the research ethics committee protocol?
A Yes, they do.
Q If we go on, he did indeed have the colonoscopy – that is at page 119. That was carried out by Professor Murch. Do the comments you have made about responsibility of the person undertaking the procedure apply equally in this case, Professor Booth?
Q We see his report:
“Appearances almost normal to caecum. Again there were minor changes in the rectum and caecum (slight changes in vascularity and prominent lymphoid follicles. The ileo-caecal valve could not be identified.”
Then, if we look at the clinical notes at page 21, we see the follow-on from that. The ward round the next day with Professor Walker-Smith:
“Colonoscopy - prominent lymphoid follicles in the caecum & descending colon
? some minor inflammatory changes
Not to have MRI or L.P.”
And there was a plan that he underwent a barium meal the next day. Just reverting to the endoscopy report at page 119, Professor Booth, I should also have pointed out that the history given prior to that procedure was of disintegrative disorder. Can I then just taken you back to page 21, please. We know as a matter of record that this child did in fact have a lumbar puncture on the 9th, and also an MRI on that day and, indeed, Mrs 12 has herself given evidence that they were carried out. We have CSF results, and an MRI scan report, all of which the Panel have already seen. I will not take you to them. Could you find any explanation as to why those investigations were carried out three days after a note on a ward round by Professor Walker-Smith that they were not be carried out?
Q Again, does the carrying out of those procedures accord with the general overall plan in the ethics committee application?
A The research protocol, yes.
Q Returning to the chronology of the admission, the next thing is a request for an EEG and evoked potentials. That is page 131. It is signed by Dr Wakefield.
“Reason for Request
Autistic spectrum disorder
+ bowel disorder following MMR”
And we see a tick by EEG and the type of evoked potentials that were required. Once again, Professor Booth, you have commented in general terms on the consequence of being a doctor who signs a request for an investigation and on your view of Dr Wakefield ordering investigations of this type in previous cases. Are your observations the same in the present case?
A Yes. I think it is inappropriate for a non-clinician, who is not a member of the clinical team, non-paediatrician, to be requesting clinical investigations on a child.
Q The fact of Dr Wakefield as a researcher ordering such an investigation, does that provide any assistance as to whether this was a clinical or a research investigation?
A It suggests that this was a research investigation, but I still think, even as a research investigation, someone with Dr Wakefield’s background and training should not be requesting clinical investigations on children.
Q Then we have the clinical histology report at page 84 and the description on the samples at the bottom of the page:
“Pieces of large bowel mucosa including lymphoid follicles with germinal centres. There is no architectural abnormality and no increase in inflammatory cells in the lamina propria. No organisms or granulomas are seen.”
Is that in effect a normal report?
Q Then, just so that you are aware of the chronology again – I do not need to take you to these but for the Panel’s benefit it is at the Royal Free Hospital records at page 22, and then 18, on the 9 January Dr Harvey goes to see the child, and makes a note the Panel will remember, saying that the child was fast asleep and that he would examine him at his home at some later stage. On 10 January there are notes by Dr Berelowitz indicating a diagnosis of “language delay ? attention deficit disorder ? features of Aspergers”. Then the child was discharged later that day after seeing Dr Berelowitz, so discharged on the 10th. The discharge notification to the GP I would like you to go to please, which is on page 111 in the GP records. This is just the brief notification, and we see under “Procedures undertaken”
Although we know that actually there were other investigations also performed. We will see the full discharge summary in a moment. Then chronologically we also know that Child 12’s histology findings were discussed at the weekly histology meeting on 15 January. We have the list for that meeting in the RF records at page 84a, which is the bottom but one of the typed bit of the list. Also, we have the conclusions of that meeting recorded in the clinical notes at page 22 in the middle of the page. Do you see where I am?
Q That is the histology meeting. They do indeed accord with what you have told us – a normal series, I think, that word is. Then we have the discharge summary. Could you turn to that, please? That is at page 32. We see that Child 12 was admitted to the Royal Free for further investigations of his gastrointestinal probs. It then sets out the history, as far as his behavioural symptoms, and his gastrointestinal symptoms as we have already gone through. He had measles vaccination at 15 months. There is reference to blood tests. A colonoscopy was performed under sedation which recorded almost normal appearances to the caecum.
“There were minor changes in the rectum and the caecum these consisting of slight changes in vascularity and prominent lymphoid follicles. The ilial-caecal valve could not be identified. Histological report on the biopsies taken on this series do not show any significant abnormality. A barium meal and follow through demonstrated lymphonodular hyperplasia of the terminal ileum.
It was notable that following the bowel clear out, prior to the colonoscopy, [Child 12]’s behaviour appeared to improve as did his soiling it is therefore conceivable that many of his problems are associated with a degree of constipation in view of this he has been started on liquid Paraffin…”.
So there we have an indication again that the histological findings had been normal and Dr Casson’s conclusion in that letter that it was conceivable that his problems were associated with constipation. Would you agree with that, on that history?
A Yes. The bowel preparation for colonoscopy is a very good treatment for constipation.
Q You have already said that the admission for colonoscopy was not clinically indicated, Professor Booth, but just of the avoidance of doubt, following that admission, is it your view that those gastrointestinal investigations, the colonoscopy and the barium meal and follow through which were carried out were clinically indicated and appropriate investigations at that stage?
A No, they were not.
Q Then there is attendance at an out-patient clinic with Professor Walker-Smith at page 22 and there is a note there which I think says that there was a continuation of the soiling and the liquid paraffin had not made a difference to that. Then we see further blood tests ordered. Could you understand or ascertain why those repeat blood tests were carried out?
A No. It is unclear why they were done.
Q Then after that, there was a letter from Professor Walker-Smith to the GP dated 25 April 1997, which is in the Royal Free record at page 31:
“Dear Dr Stuart
We have had quite a remarkable success with the use of Sulphasalazine or 5 ASA derivatives in children with autism and evidence of lymphoid nodular hyperplasia and non-specific colitis as we found in [Child 12] . I think it would be appropriate to consider a therapeutic trial of one of these agents, these drugs appear not only to help gastrointestinal symptoms but also rather surprisingly helped behavioural symptoms. I have therefore suggested that you might consider a therapeutic trial of Olsalazine 250mgs 3 times a day for [Child 12]. I would be very interested if you decide to do this to hear about his subsequent progress.”
Is the diagnosis of non-specific colitis which is apparently being made consistent with the findings documented in either the clinical histology report or indeed at the histology meeting thereafter?
A No. It is a different conclusion.
Q Can you understand why Professor Walker-Smith says that non-specific colitis was found in Child 12?
Q Can you find any reason for that diagnosis and the consequent suggestion that he should be treated with anti inflammatory apparent from any other clinical notes?
Q Does that cause you concern?
Q I am sorry if it is an obvious question, but can you tell us why?
A Something has changed the clinical conclusions from the colonoscopy/histology, the source of which is unclear; it is just not clear why the diagnosis has been changed. The opinion that this is now a non-specific colitis is not attributable to anyone, so there is no signed report in the notes. It is relevant because it appears to have led to a significant change in the management of this patient and led to the prescription of an anti inflammatory drug.
Q Professor Booth, I am not going to take you to it this time, because I have on the previous occasions, but I can tell you – and I do not think there is going to be any argument about it – the histological description given for Child 12 in The Lancet paper was indeed a chronic non-specific colitis and a reactive colonic lymphoid hyperplasia. That of course is not consistent with the clinical histology findings as reported in the records, but ties in with Professor Walker-Smith’s subsequent diagnosis of non-specific colitis in the letter to Dr Stuart. I have asked you previously as to your views as to a research finding of this kind leading to treatment. Do you repeat those, namely, that if such a course is going to be taken, it is a relatively unusual course, but if it is going to be taken, it should be clear from the records?
A It is an unusual occurrence. If it is decided to incorporate a research observation into patient management, it needs to be clear why that step has been taken, who has made the evaluation and who is taking responsibility for it. Also, it is important that if it is a research observation, it has been confirmed that it is clinically valid.
Q What exactly do you mean by that? We have already heard from Dr Davies that these were very subtle findings which would not necessarily be findings that you would make when you looked at the slides clinically. How do you confirm its clinical validity?
A Firstly, by a certain amount of scepticism about what the possible relevance of the observations might be, rather than just accepting them at face value. We know that these are mild, subtle observations which appear to have eluded an experienced group of clinical histopathologists, so these are not gross findings. You would want to be sure that your interpretation of the observation was clinically relevant and that there were not other possible explanations for these observations, which I think in these cases there may well have been.
Q If we can just go on chronologically with the follow up, because it particularly involved a decision that you question. If you would go to page 30 of the Royal Free notes first, please. This is the next letter chronologically and it is from Mrs 12 to Dr Wakefield on 3 May 1997:
I am writing with reference to your telephone call three weeks ago. You asked me to contact you again if I had not received an appointment for [Child 12] to be seen again at the Royal Free within a couple of weeks. I haven’t received an appointment yet.
You also said you would be able to write a report for me outlining the bowel inflammation [Child 12] has. I haven’t received this either yet. I understand how terribly busy you are and so please forgive me if I seem impatient. After so many years of ‘not knowing’ it is a real relief to have something concrete even though it might not be what one would hope for.”
She also refers to a sample sent to Dr Linnell for analysis of B12 and asks what the results of that test showed. This, I should say, is not remotely a criticism of Mrs 12, Professor Booth, but would you expect a parent to be writing to a researcher in relation to the results of investigations, if those investigations had been undertaken for clinical reasons?
A No, you would not. Normally the contact would be through the lead clinician.
Q Then possibly as a result of that, possibly routinely, we do not know, Child 12 did attend an out patient consultation on 30 May. That is at page 14. There is a reference to a recent chest infection and to treatment with antibiotics. Then we see the notes:
“Did try to take liquid paraffin → took it for only 2-3 weeks
→ still soiling ++
occasional abdominal pain → coincides with temperature
appetite – variable.
Abdominal examination – [nothing abnormal detected]
Discussed with …”
And those are Professor Walker-Smith’s initials –
“1. for [abdominal X-ray] to exclude constipation
2. Start olsalazine and [follow up in one month] to assess any difference
3. If constipation [no treatment] at present.”
Then he has an abdominal X-ray and that is at page 126. It says there were faeces seen throughout the colon and possibly some loading in the rectum. What did that indicate?
A That showed that the patient was constipated quite badly.
Q If we then go to page 29, please, Professor Booth, we see a letter from Dr Casson dated 2 June 1997 to the GP:
“I reviewed [Child 12] in Professor Walker-Smith’s clinic today. Basically he remains as he has previously. Unfortunately he has not persisted in taking the liquid paraffin as mum as concerned that it made his soiling worse. He still experiences occasional abdominal pain. He is otherwise well. Abdominal examination was unremarkable.”
Those are the notes we have just looked at.
“An abdominal x-ray was performed today which demonstrated marked faecal loading. I have discussed the situation with Professor Walker-Smith and we feel that we should initially start treatment with Olsalazine … “
That is the anti inflammatory. Is that correct?
“ … to assess whether this makes an effect. We should hold fire on treating his constipation.
We will review … in a month’s time at which stage it will be important to re-assess treatment and consider whether any further treatment is required.”
We know from Dr Casson that when he was reviewed a month or so later – in fact by then it was Dr Malik, the other registrar – he then reinstituted treatment with laxatives. Can you understand, Professor Booth, why in the light of the findings of the abdominal X-ray, the decision should have been made to try the treatment with the anti inflammatories, rather than the laxatives for constipation?
Q Particularly given the indications, or lack of them, for the anti inflammatories in the first place, are you critical of that decision being made?
A There is good evidence that this patient was constipated. There is good evidence from the references in the discharge summary from Dr Casson about an improvement in his behaviour after the bowel preparation, which had been a very effective treatment for his constipation, that the constipation was clinically significant in his symptoms. So it is very difficult to see why laxative treatment would be withheld, particularly as treatment with an anti inflammatory agent like olsalazine would be a bizarre treatment for constipation.
Q If the anti inflammatories were being given for the non-specific colitis, you have told us your views as to the lack of clarity as to why it was thought the child had inflammation.
A That is right, yes.
Q You have expressed the view that it would appear that the research findings in this case were driving the clinical treatment. If they were being given priority over what you have described as a rather more obvious course of treatment, are you critical of that?
A You would expect that those interventions, which were unusual on the face of it, would have been subject to a separate application to a research ethical committee. If you have a hypothesis, strange as it may seem, that olsalazine is an effective treatment for constipation, then that should be submitted to review by a research ethical committee and they would come to an independent conclusion about whether it was appropriate to expose these patients to that intervention.
Q If we just go on to 18 June at page 75, please, when Mrs 12 apparently telephoned and spoke to a nurse called Miss Thomas, who we know was a nurse who was involved in the study on these children. It says:
“ … discussed … the results of the MRI, EEG and Lp which were reported as normal. I have explained that we do have some immunology results but I am unable to interpret them. Dr Wakefield will see [Mrs 12] in clinic on 4th July. I have also explained to [Mrs 12] that ideally we need more blood for immunology (T cell subsets) and we have planned to send Emla cream through the post …”
That is in order to put a little local anaesthetic on – is that correct – before the blood test?
A That is correct.
Q Then there is reference to a review by Dr Berelowitz or Dr Lloyd Evans and:
“ … Dr Wakefield is aware of the need for a report on bowel inflammation.”
Again, is that what you would expect, Professor Booth, if this was normal clinical care, to see the results being reported with an assurance that Dr Wakefield would be seeing Mrs 12 in clinic?
A I cannot think of a circumstance where someone with Dr Wakefield’s background would need to be seeing a patient in the clinic for clinical reasons in order to be able to advise someone of Professor Walker-Smith’s experience on clinical management. Therefore one assumes that Dr Wakefield is seeing this patient for research reasons. One would certainly hope that he would not be advising on clinical management.
Q The child did indeed attend out patients on the 4th and we have the notes of that on page 14, which indicate that he is still on olsalazine, his behaviour is the same, he is opening his bowel, nothing abnormal was detected on examination, but then there is another abdominal X-ray on page 125. That also indicates faecal loading of the colon and “no underlying bony abnormality seen.” Is that also consistent with constipation?
A Yes, it is.
Q Then there is a follow on letter from Dr Malik, who was Dr Casson’s fellow registrar, to Dr Stuart, which is at page 28:
“Dear Dr Stuart
I reviewed [Child 12] in Professor Walker-Smith’s clinic today. He has been on Olsalazine for almost 4 weeks. According to mother this has not made a remarkable difference in his behaviour although he has been opening his bowels more regularly. I have not made any further appointments to see him but I have take a plain xray to ensure his abdomen is better. He needs to continue with liquid paraffin.”
So there we see the allusion to his going back on the constipation treatment.
“It is advisable that he should continue on Olsalazine for at least one year. I would be obliged if you could keep prescribing …”
And he gives the dose –
“In our experience most of the children have improved on anti-inflammatory medicines.”
Is that correct?
A That is what it says, yes.
Q In fact, somebody seems to have crossed out “symptoms” – “In our experience most of the symptoms have improved” – and changed it to “children”. Do you read it as being the gastrointestinal symptoms or the behavioural symptoms, or are you not able to fathom a guess as to that?
A I do not think one could say really. It could be either or both.
Q I am not going to take you through all the rest of the records, but there is ongoing, on and off contact with the Royal Free Hospital thereafter. Can I just turn to the general questions which I have asked you, Professor Booth? Does it appear to you that these gastrointestinal investigations were being carried out overall for clinical or research reasons?
A They started as research investigations and led on to further investigations: the abdominal X-rays, for example, which were clinically indicated.
Q As far as the neuro developmental side of things, we know the child was assessed by Dr Berelowitz on 10 January and by then the colonoscopy and the other investigations had been carried out. In the event, Dr Berelowitz made a diagnosis of language delay or attention deficit disorder with features of Asperger’s. Do you have any views as to the appropriateness of that order of investigations?
A The assessment of eligibility for inclusion in the study should have been carried out before the invasive investigations were performed. As it turned out, Dr Berelowitz did not think this patient had disintegrative disorder anyway.
Q Thank you, Professor Booth. That is all I have to ask you about that child and I am turning on to Child 8, if you could find your report and refresh your memory. Sir, the Panel will need the GP and Royal Free records for Child 8. Going on now to child 8: first of all the referral and the first note we have in relation to that is at page 28 of the GP records. We see that that was a telephone call from the GP on 30 September, middle of the page:
“Mum taking her to Dr Wakefield, Royal Free Hospital for CT scans, gut biopsies ? Crohn’s. Will need referral letter. Dr Wakefield to phone me. Funded through legal aid.”
There was a formal referral letter on 3 October 1996, and that is in the Royal Free records at page 21. That is a letter to Dr Wakefield from Dr Jelley, the GP:
“Dear Dr Wakefield,
[Child 8]’s mother … has been in to see me and said that you need a referral letter from me in order to accept [child 8] into your investigation programme. I gather this is a specific area of expertise relating to the possible effects of vaccine damage and her ongoing GI tract symptoms. As far as I am concerned if [Mrs 8] is happy to proceed with this and it gives her any further information and peace of mind I am sure it would be beneficial for both her and [child 8].”
She encloses photocopies of some recent correspondence giving an idea of child 8’s current state:
“I would simply reiterate Dr Houlsby’s recent comment that both the hospital and members of the Primary Care Team involved with [child 8] had significant concerns about her development some months before she had her MMR vaccination. I take Mum’s point that she has video evidence of [child 8] saying a few words prior to this vaccination being given and her vocal abilities are now nil but I don’t think we can be entirely convinced as yet the vaccine is the central cause of her current difficulties. However, I am quite prepared to support [Mrs 8] in her quest for further information and I hope some useful results come from these tests.”
Accompanying that was a sheath of correspondence. I am not going to go to it in great detail. It undoubtedly refers to both behavioural problems and gastrointestinal problems but just so we know where it is and what it says, Professor Booth, page 23, a letter in February 1995 from a consultant paediatrician, Dr Houlsby, in particular gastrointestinally, third paragraph down:
“She was recently admitted to the ward following a febrile convulsion in association with gastro-enteritis.”
The rest of it refers to global developmental delay.
At page 27 is a letter from the special needs team, the second page of the letter is at page 26. On page 27 there is reference to an episode of very loose stools, at the top of the page:
“… mother reported that [child 8] has been unwell with bouts of very loose stools, however, the specimens were clear. She has also been noticed to twitch in her sleep.”
Other problems are mentioned there.
At page 28 is a letter from a consultant in clinical genetics which says:
“ … [child 8]’s mother’s concerns that her problems stemmed from her MMR vaccination at 10 months. She tells me that … [she] was very poorly [after] it …”
and that since then she has had behavioural difficulties:
“She has been in touch with an organisation Jabs and is in contact with a mother of a child who similarly feels that her child’s problems date from the MMR immunisation.”
There is also a letter from Dr Houlsby to the GP at page 25. In the third paragraph of that letter Dr Houlsby indicates that he is arranging for the child to have an EEG. She had had one previously which had been normal. The letter goes on to set out the history of developmental delay and fever-associated convulsion in the context of a diarrhoeal illness associated with a fever two weeks after having the MMR (page 25a).
There is obviously a history of diarrhoea there, and I think in those circumstances, Professor Booth, you accept that her referral to a gastrointestinal centre would be a reasonable thing to do?
Q Would that necessarily mean the Royal Free?
A No. If you are up in XXX you would travel by a number of good centres of paediatric gastroenterology before you got to London.
Q Dr Wakefield then wrote to Professor Walker-Smith, and that letter is at page 35:
“Please find enclosed some details of the girl who was referred to me with secondary autism and bowel problems. I requested that a letter of referral be sent to you and I hope that this has been done.”
He confirms the referral and some further details.
Then Professor Walker-Smith writes to Mrs 8 at page 22 on 3 December 1996:
“Dear [Mrs 8]
I have had documentation concerning [child 8] and I have heard that you would like us to go ahead with the investigations. I have arranged for [child 8] to be admitted to Malcolm Ward on the afternoon of Sunday 19 January 1996. the colonoscopy will be the next day and other investigations will be arranged during the week. [Child 8] would be able to go home on the Friday or Saturday.”
As far as that is concerned, it would appear that a decision had been made by Professor Walker-Smith that this child was going to have a colonoscopy; there had not been any outpatient admission, and you have seen the nature of the information that he would have had in relation to gastrointestinal symptoms: do you regard that as an appropriate course of action?
A No, I cannot understand the decision just to admit the patient for a colonoscopy.
Q Could these symptoms ever be said to have been of a sufficient degree to justify making such a decision without an assessment of the child, if it is for clinical as opposed to research reasons?
A No, not with the minimal information that appeared to be available to Professor Walker-Smith at the time.
Q You say you cannot understand it for clinical reasons: what is it consistent with?
A It is consistent with this patient being admitted for entering into a research protocol, particularly as Professor Walker-Smith’s letter to the mother refers also to other investigations being arranged during the week.
Q You have said you would have expected the child to be seen in outpatients: is this a case where you would expect some sort of screening tests to have been carried out?
A Yes. I think given the nature of the symptoms that are recorded in the notes before this referral was made, they are not of the type where you would immediately think that a colonoscopy was going to be a first-line investigation.
Q I should have pointed out that the letter to the mother simply saying that the child was to come in for colonoscopy and the other investigations was copied to, amongst other people, Dr Wakefield. In any event, no screening tests were carried out. They were ultimately done after the colonoscopy, and we will come on to look at the results chronologically if we may. The child was admitted to the Royal Free under Professor Walker-Smith on 19 January and remained in until 28 January, and the admission clerking note is at page 7. We can see at the top that the problem was identified as “developmental delay and diarrhoea for the last one and a half years” and then going down to “Development”: it was thought that developmentally she was always a bit on the slow side as compared to her elder sister.
Further down it says: “By 18 months she was saying 2-3 words and walking” and then she had her MMR and within two weeks of having the MMR she had a diarrhoeal illness and a febrile convulsion and she remained in hospital for five days.
I should point out, Professor Booth, that the date at the top of the page is 1996, but that is plainly a “January mistake” because in fact the child was admitted in 1997.
There was a history of deterioration thereafter in this child. The next paragraph:
“About the same time she developed diarrhoea which continued for more than one year. 5-6 loose stools per day. According to mother she tried Primrose Oil in November and her diarrhoea got better.
… last few months her behaviour has improved and she is sleeping better.”
That was the history that was obtained, and I will ask you about that in a moment. She went ahead, we know, and a colonoscopy was carried out, and we have the consent forms in the form we have become accustomed to, the clinical consent form for the colonoscopy and a consent form for research biopsies. The handwritten colonoscopy report, which is in the Royal Free records at page 93 says the appearance was normal except for a mild increase, I think that is, in lymphoid tissue in the terminal ileum, and the plan we see is “Dr Wakefield protocol”: does that assist as to your views as to whether this was a clinical or a research admission?
A It is consistent with this patient having been admitted to take part in the research protocol.
Q The blood tests which you said should have been taken before all this was embarked on had the child been sent on outpatients were taken on the same day as the colonoscopy and the full blood count report is on page 73, and then there are further results on page 78, and the albumin is on page 69, if you need to look at that. Are there any abnormalities in those results?
A The albumin on page 69 is shown as being a bit high but what you are looking for here is a low albumin so that is not significant.
Q You mean “looking for” if it is an indication of inflammation?
A If it was low it would be consistent with some gastrointestinal inflammatory process. The full blood counts on page 73, including the ESR, is normal, and on page 78 there are a number of variables that are outside the normal range but they are not things that would make you think this patient had inflammatory bowel disease.
Q There is then a request for the child to be seen by Dr Berelowitz, and after that a note of a ward round with Professor Walker-Smith, which is at the top of page 9, 23 January: we know the mother had said that the Evening Primrose had sorted out the gastrointestinal problems but here we see “behaviour deteriorating since Evening Primrose stopped. Awaiting MRI, EEG, Dr Berelowitz, histology” and then we can see that she had a barium meal and follow through which looked normal. As far as Dr Berelowitz is concerned, the note for a request for him to see the child is at page 20. We see there:
“Problems: 1. Developmental delay … [child 8] is in Malcolm Ward for this week for investigation of ? disintegrative disorder/enteritis syndrome.”
With regard to the histology results, at page 61 :
“… fragments of poorly orientated, but normal small bowel mucosa. A lymphoid reaction centre is seen in each sample”.
In the other three samples:
“These are all pieces of normal colonic type mucosa containing occasional lymphoid aggregates. Minimal inflammatory changes may be the result of operative artefact.”
Can you tell us what operative artefact means, Professor Booth?
A No, it is not really a term that I am familiar with, I am afraid.
Q Would it be indicative of any significant abnormality in any event?
A No, I would not have thought so, no.
Q One thing I should point out, because you may be asked about it, is it says at the top of the page, under the clinical details, “Diarrhoea – blood. ? mucus.” Is there anything that you have seen in the records which indicate that this child’s history had in fact included any indication of blood?
A No, not that I am aware of.
Q After the histology report we have some details in relation to that. We have got Dr Davies’s list on page 61A, and we see this child’s name fifth down in the list, and a note by Dr Davies of nothing abnormal having been detected, as far as she was concerned at least, and that is borne out by the clinical records which also indicate that in the histology meeting the histology was normal, and that is at the bottom of page 9.
Q Returning to the chronology of the admission: there were evoked potentials, which took place on 23 January. There was an MRI on 24 January, and both of those had normal results, and we know that Dr Berelowitz did indeed see child 8 during that admissions as there is a letter from him to Professor Walker-Smith, dated 28 January, and that is at page 18. The conclusions are at page 19, saying:
“I note that following the vaccination there was a period of fever, diarrhoea and developmental regression. I am therefore left wondering whether in fact she had a post vaccination encephalitis rather than anything more complicated than that. I don’t think autistic spectrum diagnosis is merited here.”
The child was discharged on 28 January.
Turning to the clinical indications for those gastrointestinal investigations, Professor Booth, there is one other reference I should have taken you to.
I took you to the one reference in the records to blood on the histology report. If we go to the request for the report at page 60a, we see that under “Clinical details”, it says:
“Diarrhoea – [no] blood ? mucous”
So we have those details. You will recall that we have the original clerking notes, indicating a history of diarrhoea and an indication from the mother that the diarrhoea was better as a result of the evening primary oil that had been given since November. In those circumstances what is your view as to whether there were clinical indications for colonoscopy in this case?
A No, there were any indications for a colonoscopy at that time.
Q Given the history that was elicited when the child was admitted for the colonoscopy, how relevant was that to any subsequent decision for her to undergo it?
A The history suggested that the patient’s diarrhoea had stopped at least two months before the admission, which might have been detected had she been seen in the outpatient clinic before being admitted. So it is difficult on that basis to see why she would have had a colonoscopy.
Q What is your conclusion as to the reason why she underwent the investigations that she did?
A The background, whereby she was seen at the Royal Free with Dr Wakefield on the face of it soliciting the referral, the reference to Legal Aid funding, the reference to inclusion in an investigation programme, the investigations that she had, that conformed to the research ethics committee application and the absence of a valid clinical indication for the investigations would suggest that this was a research study.
Q You said, you see no reason why it was clinically indicated for her to undergo a colonoscopy. We know she had a barium meal and follow through as well. Does the same criticism apply?
Q Just continuing the history and follow up, there is then some correspondence from the solicitors involving the MMR litigation, confirming that the child had legal aid, and there is then a discharge summary to the GP, which is at page 15, just indicating the child was admitted on 20 January for further investigation of a possible association between developmental delay, gastrointestinal symptoms and vaccination. It sets out her behavioural history, the fact that she had her MMR. Coincidentally with this she developed diarrhoea which continued for over a year, passing five to six loose stools a day.
“She was given primrose oil in November 1996 and subsequently her diarrhoea improved.”
It then sets out the results of the colonoscopy.
“All pieces of colonic tissue demonstrated minimal inflammatory changes.
A barium meal and follow through was normal, as was an MRI scan.”
It sets out the blood results and indicates at the end:
“These results therefore are no indicative of marked ongoing inflammation. The results from Dr Wakefield’s specific investigations concerning the measles antibody would be available from him.”
I want to go on, just to look at what happened thereafter, bearing in mind that indication, that none of the results were indicative of marked ongoing inflammation, because the next thing that we see is a letter from Dr Wakefield to the GP, which is in the GP’s records on page 74:
“Dear Dr Jelley,
I have recently been contacted by [Mrs 8] and realise that we have not spoken for some time. We are now coming up to the 38th child investigated for this sy6ndrome and the findings have been remarkably consistent. Please find enclosed the first paper covering the initial 12 children, including [Child 8].”
That, of course, is The Lancet paper.
“This is due for publication in The Lancet in the next few weeks.
We have had some success (striking, in some cases) in treating these children with mesalazine. Both gastrointestinal and behavioural improvement have been noted. I have written to Professor John Walker-Smith suggesting that we start [Child 8] on mesalazine, and he will be writing to you in the near future.”
I just want to go to the rest of the sequence of the ultimate prescription, Professor Booth, and then ask you what your views are on this series of letters. We then have a letter from Dr Wakefield to Professor Walker-Smith and that is in the Royal Free Hospital records, please, at page 14.
[Child 8]’s mother has phoned me to say that her gastrointestinal symptoms are particularly severe at present. I note that she has changes typical of the syndrome in her gut all though they are mild. She has not received any 5-ASA and I think she would be an ideal candidate for mesalazine. If you decide to put her on this, Jill and I”
- that is Jill Thomas, a research nurse –
“will keep in touch with [Mrs 8] and Dr Jelley, the General Practitioner, to monitor progress in view of the long distances involved.”
Then there is a note of a telephone conversation between Dr Jelley and Dr Wakefield, and the note was made by Dr Jelley. She says she thinks that Dr Wakefield initiated that call, but she cannot swear to it. I will not take you to it, but just for everyone’s records it is at page 28, and the note says, “Telephone Dr Wakefield ? needs mesalazine. Await letter.” Then lastly, there is a letter from Professor Walker-Smith to Dr Jelley – we are in there Royal Free records at the moment, so we will continue there. That is in the Royal Free records at page 13:
“I understand that [Child 8] continues to have gastrointestinal symptoms. I do believe that it would be appropriate to give /9 a therapeutic trial of the 5-ASA derivative of Pentasa in a dose of 500mg daily.”
First of all, is Pentasa a form of anti-inflammatory, as is mesalazine?
A Yes, it is.
Q Are they interchangeable for these purposes?
A No. Mesalazine is the generic name for a particular group of 5-ASA compounds, one of which is Pentasa.
Q We know from the records that in fact this child was indeed then started on mesalazine. Is the recommendation for treatment with anti-inflammatory therapy consistent with the clinical histology findings and the notes of the histology meeting that we have already looked at, namely that there was normal histology?
A The conclusion of Dr Davies was that the changes were normal. I think the discharge summary said “Minimal inflammation” and went on to say something about there not indicative of marked ongoing inflammation.
A So again that background, immediate prescription of an anti-inflammatory agent would be most unusual, I think.
Q Again, this is another instance of what we have already discussed, I know, Professor Booth, but is it important in your view that the reason for treatment is evident from the clinical notes?
A Yes, very much so.
Q What is your view as to Dr Wakefield’s role in relation to the recollection of treatment for anti-inflammatories and, indeed, his writing and advising that to Professor Walker-Smith and his offer to follow up the effects of the treatment in this child?
A It puts Dr Wakefield into an inappropriate clinical position in which he is generating advice on management and, as you say, offering to follow the patient up. I cannot think why Professor Walker-Smith would need advice on managing a patient with gastrointestinal inflammation, as it was perceived by them, I assume, from someone like Dr Wakefield.
Q Sorry – did I interrupt?
A No. It is all right.
Q I was only going to ask you, as I have asked you previously: you have highlighted Dr Wakefield’s lack of paediatric qualifications already and, indeed, the terms of his employment at the Royal Free. Are you critical of his involvement in this way?
A Yes, absolutely. It is completely inappropriate.
Q Just completing the history in relation to follow-up, page 59 of the GP records, please. We see a letter from the consultant psychiatrist saying:
“I saw [Child 8] a year ago at which point the parents had decided to abandon …”
- a drug that he had prescribed. Then he says:
“Apparently mesalazine did not help either her bowel or her behaviour. Although, from her mother’s reports, I thought she had improved substantially at that time, [Mrs 8] is now more doubtful. In retrospect, she thinks that she was probably focusing on [her] positive points….”
And then relating it to educational aims for the child. I think I am correct in saying – and I shall be told if I am wrong – that there is no further involvement of the Royal Free Hospital in relation to this child. All in all, clinical or research, Professor Booth, for this admission and investigations?
A This has all the hallmarks of a series of research-driven investigations.
Q Again, as far as any diagnosis of disintegrative disorder prior to the investigations being carried out, can you see that any attempts were made to obtain that?
MS SMITH: Sir, I see it is quarter past eleven and that is the end of two children, if I can put it like that. You may feel it is appropriate for us all to have a break.
THE CHAIRMAN: Yes, I think we will need a break and I am sure Professor Booth would welcome a break at this stage as well. We will now have the mid-morning break.
Professor Booth, you are still under oath and in the middle of evidence. Please do not discuss anything.
THE WITNESS: Yes, sir.
THE CHAIRMAN: We will resume at twenty-five to twelve.
(The Panel adjourned for a short time)
THE CHAIRMAN: Ms Smith?
MS SMITH: Thank you, sir. Professor Booth, could we look at Child 7, please. You will need your report for that child, and the Panel will need the GP records and the Royal Free records.
The referral circumstances, first of all, Professor Booth, remembering that this little boy is the brother of Child 6] and he was referred in December 1996 after his brother. Could we turn, first of all, to the GP records at page 282. This is to Professor Walker-Smith from the GP.
“I would be grateful if you could see this boy who is a child whose brother you have recently investigated as part of your programme for colonoscopy for children with autistic problems. He himself probably does not have autism, although this is not certain at present but he does have convulsions which I believe may make him eligible for your study. He also suffers with bowel problems similar to his brother who is autistic.”
Professor Walker-Smith writes back to the GP, indicating that he would be pleased to see the child, and arranging an outpatient’s appointment. Then there is an outpatient’s consultation. Could we look at the notes for that please, and turn to the Royal Free bundle. You will be in that for a little while now. It is page 11. The only relevant gastrointestinal symptoms are that at 2 years blood and constipation alternate diarrhoea with mucous. Then we have the letter that Professor Walker-Smith sends to the GP at page 60, dated 17 January 1997.
“Many thanks for referring [Child 7]. I was very interested to hear the history of this child in which there does seem to be a clear relationship between symptomatology and the MMR. He had the MMR rather later than usual at the age of 21 months. His mother tells me 24 hours afterwards he had a fit like episode and slept poorly thereafter and she attributes changes in his behaviour to this event. I understand that he has not been fully investigated although I understand it is your opinion that he could be within the autistic spectrum although it is not your view that he does have autism.”
There is an abnormal EEG. Then he says:
“From a gastrointestinal point of view from the age of 2 he has had intermittent episodes of passage of blood associated with constipation and diarrhoea with mucous. His mother says he has intermittent high fevers although I understand that he has had recurrent ear infections which have been treated by antibiotics.”
There is intermittent vomiting at night. Cries a good deal at night. And then he goes through his diet being inadequate.
“… nevertheless he is gaining weight and growing satisfactorily and is on no particular dietary restriction. …
Particularly in view of the findings in his brother, I think it would be appropriate for this child to be investigated particularly by colonoscopy and I am arranging for him to be admitted on Sunday 26 January 1997 and he will be having other investigations as part of the protocol. We will let you know the results of these investigations in due course.”
And that letter was copied to Dr Wakefield. Leaving aside the symptoms for a moment, Professor Booth, to which, of course, I will be returning, bearing in mind the references to it being appropriate to investigate the child, particularly in view of the findings relating to his brother, and to him having investigations as part of the protocol, does that suggest to you whether the admission was in fact clinically or research-driven?
A It is pointing very strongly to a research driver.
Q There is no mention of conducting tests for inflammatory markers prior to admission for colonoscopy in this case, but I think it is the case that, bearing in mind the history which Professor Walker-Smith obtained in this case, particularly the episode of the passage of blood, are you critical of the course which was adopted? Asking it in another way, would normal inflammatory markers anyway deter you from proceeding to colonoscopy in this case?
A I think you would probably do some investigations, but I think with blood and diarrhoea in the mucus, your threshold for doing a colonoscopy would be quite low here, yes.
Q As far as any other investigations are concerned, we know there was a history of constipation as well. Given that history, would one proceed immediately to colonoscopy, or are there any other preliminary investigations that you would have undertaken first?
A I think with that history of alternating constipation and diarrhoea and blood, I think you might, as well as checking his inflammatory indices, done a plain abdominal film to see if the main problem was constipation, given that, as we have discussed, diarrhoea can occur spuriously with constipation and children with constipation can pass blood p/r.
Q If an abdominal X-ray had been undertaken and it had confirmed constipation, in such circumstances, how would that affect the decision to proceed to colonoscopy?
A I think you would deal with the constipation first and satisfy yourself that the constipation had resolved and then reviewed the symptoms, if any, that the patient was left with. If it was demonstrably the case that they were no longer constipated and yet were continuing to have diarrhoea with blood and mucus, then I think you would want to go on and do a colonoscopy.
Q As far as not carrying out the abdominal X-ray at a preliminary stage is concerned, are you critical of that?
A Yes. It would have been my practice, I think, to have done some preliminary investigations before just deciding on a colonoscopy.
Q This child was admitted to the Royal Free and we know the dates of admission are 26 January 1997 to 1 February. Again, the notes record that was under Professor Walker-Smith’s care. If we look at page 6 – and, as I say, we will return to the clinical indications for the colonoscopy – you accept that these particular symptoms were consistent with colonoscopy as an investigation, but you have also expressed the view that this looks like a research admission. If we just look at the notes from the out patient clinic, we see:
“Admitted to Malcolm Ward for colonoscopy and investigations as part of the disintegrative disorder colitis study.”
Then going down the page, we see:
“Bowels, severe constipation, blood mucus to diarrhoea, alternates.”
Then I think the next entry is “No blood.” Presumably that means no blood with the diarrhoea. How would you read that?
A It is uninterpretable.
Q “Had MMR late”. Then, “Constipation became worse. Began to complain about it.” Then further down, under the word “Now”, “diarrhoea and the fact that he had had a “funny turn” Then if you go on to page 7, in the middle of the page:
“Impression: Funny turns and altered bowel habit
[possibility of] ulcerative colitis or Chron’s
+ ? petit mal”
Which is presumably a reference to the funny turns.
Q Then “Plan: Colonoscopy”; then “Autism protocol.” We then have the consent forms, simply a consent form in this case for colonoscopy and biopsy, at page 107. I think that is in the standard form, is it not?
Q Continuing with the chronology, going back to page 7, at the bottom of the page, there is a ward round with Professor Walker-Smith noted:
“For colonoscopy today
For [barium meal and follow through Wednesday]
To see Dr Berelowitz re autism
Dr Lloyd-Evans re developments”
As far as we can ascertain, the plans in relation to Dr Lloyd Evans were not carried out, but was the rest in accordance with the ethics committee application protocol?
A They are included in the application, yes.
Q Thereafter there is another consent form for research biopsy; I will not go into a form we have looked at previously. The colonoscopy was performed that same day, 27 January. That is at page 109. That form gives a history of disintegrative disorder and the results say:
“Slight evidence of vascular abnormality in rectum and sigmoid but otherwise essentially normal. The terminal ileum however demonstrated a marked degree of lymphonodular hyperplasia.”
That colonoscopy was carried out by Dr Thomson. There were blood tests done and the results were obtained subsequent to the colonoscopy. I think it is right, for reasons you have given previously, namely, the history of blood, that even if the inflammatory markers had been normal prior to colonoscopy, it would not have deterred you from undertaking the procedure in this particular case.
A Not in this instance, if the other investigations, excluding in particular constipation as being responsible for these symptoms, were negative.
Q Then we have a request for EEG and evoked potentials. That is on page 157. Disintegrative disorder and inflammatory bowel disease, EEG and the nature of the EPs are set out and it is signed by Dr Wakefield. If this had been a solely clinical admission for colonoscopy for a child with symptoms which you accept would indicate that as an appropriate investigation, would you expect to see investigations of this kind being ordered by Dr Wakefield?
A No, I would not.
Q Do you have the same criticisms as you have made previously in relation to the role in ordering investigations?
A Yes, I do.
Q Can you see any basis for the diagnosis, if that is the right word, in the reason for the request, of disintegrative disorder?
A There is no evidence that I am aware of that this patient had disintegrative disorder.
Q Then continuing with the chronology, we have a barium meal and follow through and the results of that at page 111:
“ The small bowel appeared normal. Small filling defects are seen in the terminal ileum consistent with lymphoid nodular hyperplasia.”
Again, just stopping there, leaving aside the failure to carry out an abdominal X-ray as a preliminary investigation which we have already discussed, in light of the history and particularly the blood, in this case do you think that there was a clinical indication for both the colonoscopy and the barium meal and follow through to be carried out?
A Yes. If you think that the colonoscopy is probably clinically indicated, with the reservations we have discussed, then a contrast study like this would also be an appropriate test.
Q It has been pointed out to me, Professor Booth, that perhaps I ought to take you to the blood test results, which I think showed some minor abnormalities. That is at page 110. Can you just tell us – it is of limited relevance, but it is a factual matter which has to be covered in the charges – do they in fact reveal some abnormalities?
A There are some abnormalities there, yes.
Q Are they highly significant or minor?
A The haemoglobin of 10.6 has gone down to 9.4 a few days later. I cannot remember how that ties in with the colonoscopy, but that is a substantial reduction, although the 10.6 might have been taken at a time when the patient had had a lot of bowel preparation and was a bit dry. It is a bit difficult to say. The white count is a bit high, the ESR is up a bit, platelets are normal.
Q The colonoscopy was on the 27th, the day before.
A It is difficult to know why there is a change in the haemoglobin of over a gram, which would be unusual unless the patient had bled, but I do not think there is any record of that in the notes. I cannot explain that reduction in the haemoglobin and I cannot see a C reactive protein.
Q It is one up from the bottom, I think.
A Sorry, yes. CRP. That is normal.
Q Returning to the chronology, we have a ward round with Professor Walker-Smith on 30 January at page 8. We see it says in the third line down:
“Has chronic constipation”
“Plan – full blood count, blood cultures
- ? start on sulphasalazine
- if biopsy shows inflammation”
Then a reference to lactulose. Underneath that, on the same day, it indicates he is to be seen by Dr Berelowitz. We know the lumbar puncture was undertaken on that same day, because we have the CSF results. I will not take you to them, but they are on page 118 if the Panel want the reference. Then the histology results begin at page 149, with the conclusions at page 150. Under “Comment’, we see:
“Small bowel biopsy and large bowel series without significant histological abnormality.”
We have the histology note in the clinical notes of the histology meeting between the histopathologists and clinicians on page 8. On 31 January, histology is noted as normal. Is that correct?
A That is right, yes.
Q Returning to the chronology of the admission on that same day as the histology meeting, 31 January, the child had an EEG in accordance with Dr Wakefield’s request and that was normal and he was discharged on 1 February. The investigations which were in fact undertaken were therefore colonoscopy, barium meal and follow through, MRI, LP and EEG. Again, do they appear to correlate with the programme of investigations listed in the research protocol?
A They conform to that list, yes.
Q I want to ask you about the follow-up, because that involves the prescription of therapy, bearing in mind the histology results and the histology meeting I have taken you. If we go to page 4, please, which is a printout, we can see that there was an out-patient appointment with Professor Walker-Smith on 16 April 1997. Then the record of that out-patient appointment is on page 13. We see in the middle of that note, under the “On examination” details:
“Although colonic histology was normal he had significant lymphoid nodular hyperplasia”.
Thereafter, Professor Walker-Smith wrote to Dr N at page 59, dated 17 April 1997:
“Dear [Dr N]
I am sorry that we have not yet had the discharge summary sent to you for [child 7]. Basically though, he had lymphoid nodular hyperplasia but on this occasion no evidence of inflammation in the distal bowel. Nevertheless he continues to have symptoms, although these are chiefly behavioural. When I reviewed him in the clinic I thought it would be helpful to try a therapeutic trial of Olsalazine in the same dose as for his brother … and then to assess whether we need to continue.”
He also indicates that he was following up a low serum IgA result:
“I will be reviewing him again with his brother in 4 months time.”
That was copied to Dr Wakefield.
Perhaps I should have asked you this before but perhaps it is particularly relevant to this patient, are there any potential side-effects in taking anti-inflammatories, in particular Olsalazine?
A There are side-effects. The one in particular with Olsalazine is that about 10 per cent of patients get loose stools as a result of it – sometimes it is quite bad diarrhoea. There are other side-effects like headache and skin rashes and also in the longer term potential problems with 5ASA affecting the kidneys.
Q Can you understand the rationale for giving this child Olsalazine, given Professor Walker-Smith’s own indication that he had no evidence of inflammation in the distal bowel and that his symptoms were chiefly behavioural?
A I cannot explain it I am afraid, it is a very unusual – in my experience unique – use of Olsalazine in this clinical circumstance.
Q Do you think it is an appropriate clinical indication: if the decision was based, as it appears to have been, at least to some degree, on the fact that his brother was having it, do you think that is an appropriate clinical indication for such a prescription?
Q It is an anti-inflammatory, as you have described, and Professor Walker-Smith seems to be saying that though he had apparently detected some lymphoid nodular hyperplasia which in the histology meeting had been recorded as normal, but assuming that he did, he is also saying that he had no evidence of inflammation, so is there a logic that you can see?
A Both lymphoid nodular hyperplasia and behavioural abnormalities would each be a novel indication for prescribing Olsalazine.
Q Continuing with the history: the same day as he wrote that letter, 17 April, he wrote to Dr Berelowitz and that is at page 84:
“[Child 7] is the sibling of [child 6], a child in our autistic study. In [child 7]’s case the study did reveal some lymphoid nodular hyperplasia but the histology of the distal bowel was normal. However, as he is currently symptomatic, I have empirically commenced him on Olsalazine in a dose of 250mg three times a day as his brother had done so well on this medication.”
He then says there is some confusion as to what his behavioural diagnosis is in the context, and asking whether he could be reviewed.
It is clear that at that point Dr Berelowitz had not seen this child.
At page 271 in the GP notes there is a request from Dr Bennett, who is the consultant community paediatrician, asking for information:
“I know that these 2 young brothers have attended your clinic at the Royal Free Hospital I understand that [child 6] has had a diagnosis of inflammatory bowel disease …”
and saying there were concerns about a number of symptoms which mother had been reporting in relation to both children and saying:
“It would be very helpful to have information about his bowel condition and the treatment he is receiving as [Mrs 6 & 7] has requested that this is included in his educational statement …”
After that we get Dr Casson writing what is effectively a discharge summary to Dr Bennett and that is at page 57 of the Royal Free records. This deals with both the children, so if we can go on to child 7, who is at page 58:
“With regard to [child 7]: he was referred to Professor Walker-Smith by Dr N. He is not thought to have features of autism. There was concern over a previous fit-like episode which occurred 24 hours following his measles vaccination. There was also concern that from the age of 2 years he had intermittent passage of blood PR with alternating constipation and diarrhoea.
It was decided in view of the findings in his brother to investigate [child 7] further. He was therefore admitted for a colonoscopy on 27 January 1997. This demonstrated very mild evidence of vascular abnormality in the rectum and sigmoid but otherwise essentially normal. However, the terminal ileum demonstrated a marked degree of lymphoid nodular hyperplasia. Histology from this procedure was reported as normal.
When [child 7] was seen subsequently by Professor Walker-Smith in clinic he felt that a therapeutic trial of Olsalazine was indicated. This was empirical treatment chosen as mum had reported a marked improvement in [child 6].”
That sets out the history that we have already looked at and subsequently we know that this child attended an outpatient consultation with Dr Berelowitz, and there is a diagnosis from Dr Berelowitz, and we had better go to that briefly, it is in bundle FTP2. Page 605g sets out the history, and the diagnosis is on the second page:
“… I do think that [child 7] suffers from a developmental disorder, perhaps somewhere between Asperger’s and autism. However, I would want Andrew Lloyd Evans’ ” – the developmental paediatrician at the Royal Free – “views on the development following the febrile convulsion. I also retain some uncertainties about the strength of the conclusion that we should draw from some of the historical features.”
That letter was in fact sent to Dr Wakefield, Professor Booth. Again, is that what you would expect if it was a clinical referral?
A No I would not expect any involvement of Dr Wakefield in clinical matters.
Q Indeed, we see from the beginning of the letter, not only is it addressed to Dr Wakefield but the first sentence is: “Thank you for referring [child 7] to me.”
Returning to the history: following his admission to the Royal Free, there is a very lengthy history indeed in relation to this child and I am only going to take you to a selected few documents simply to complete the story: 16 July 1997 we have Professor Walker-Smith writing to the GP having seen the child in outpatients, and that is at page 56:
“His mother says he continues to have diarrhoea now up to 4-5 times a day and a week ago he had an episode of blood and mucus in the stools which settled spontaneously. This is a bit surprising as he continues Olsalazine …”
He gives details of the way that was being taken:
“His behaviour is much more testing but he is much livelier than before … This is really quite notable. When I examined him myself I could have quite a lovely conversation with him. [Mrs 7] has believed has ‘woken him up’. She also says that he also has very few petite mal attacks since he started on Olsalazine. Whether this is coincident or not is hard to judge as indeed is all this kind of response to this therapy. I would like to continue to review him and see him in clinic in 4 months time.”
In the GP Dr Casson writes, having seen him again, at page 254 saying that an abdominal X-ray had been performed on the child. It was performed to see if there was evidence of faecal loading, and he had no significant pathology but Dr Casson was recommending that an ultrasound of the abdomen should be carried out. Then he says:
“I note our previous communications in which [Mrs 7] was concerned that the Olsalazine despite improving [child 7]’s behaviour seemed to worsen his diarrhoea. She therefore has been through a procedure of stopping the Olsalazine to see if his symptoms changed and once again restarting it. The outcome of this has been that he has been off his Olsalazine and we should await to see how the situation develops. Nevertheless, if his diarrhoea persists we will be happy to review him in our clinic.”
So if Mrs 7 thought that his diarrhoea was being worsened by the use of Olsalazine would that be something which might be the case?
A It would certainly be consistent with one of the recognised side-effects of Olsalazine.
Q Going on to the Royal Free records at page 54 – by now we are in January 1998 – and Professor Walker-Smith is writing to the GP saying he has reviewed the child again; that he had large lymph nodes but there was no evidence of colitis:
“He was tried for a time on Olsalazine but this was stopped as it appeared to cause diarrhoea. At the moment this child is passing one stool a day but plain x-ray of the abdomen also shows quite marked faecal loading. I have therefore commenced in on Lactulose …”
Lactulose is for constipation is that correct?
A That is correct, yes, it is a laxative.
Q On the next page he says:
“I do not believe that [child 7] should be followed further at the Royal Free as the main practical problem gastrointestinally is to try and help with his constipation. Lactulose in the first instance may be satisfactory but he may need more powerful medications. I would recommend again that it may be best that he may be seen on follow-up by a consultant paediatrician in XXX.”
Despite that he appears to have gone on as an outpatient at the Royal Free, and he sees Professor Walker-Smith again in August 1998 and Professor Walker-Smith writes to the GP again saying that the child has chronic constipation (page 53 of the Royal Free records). He suggest Lactulose again:
“If there are further episodes of constipation otherwise we will be reviewing him … in six months time.”
Then he writes to Dr Wakefield at page 64:
“[Child 7] [has] an interesting history that 6 weeks ago he had an episode of quite severe abdominal pain which lasted several hours. It was so severe that his mother took him to the hospital to check for appendicitis. There was no evidence of this and it has settled down. He is currently on no medication at all because the Olsalazine merely passed through and you will recall that he had lymphoid nodular hyperplasia with a histoligically normal colon … the reason for writing to you particularly at the moment is the fact that we repeated his urinary amino acids which were still strongly abnormal … Perhaps you might care to discuss this with the biochemists as to whether this is relevant and whether we need to pursue it further.”
There is then reference to skin prick tests to be arranged on the next visit.
Again, Professor Booth, if this was the normal follow up from a clinical investigation would you expect to be seeing these sorts of communications between Dr Wakefield and Professor Walker-Smith?
Q If we go back to the GP records we see at page 215 that Dr Wakefield writes a general letter, “to whom it may concern”, confirming that:
“… [Master 7] is one of a number of children investigated at the Royal Free from a newly identified syndrome comprising chronic bowel inflammation and autism. The long term natural history of this condition is yet unknown but it is likely that the bowel disorder as well as the autism will require long term medical supervision.
It is notable that the novelty of this syndrome and the lack of understanding of the origins of developmental disorders in children has often led to conflict between parents, the medical profession and the various authorities.”
We see at the bottom that it was dictated by Dr Wakefield and signed in is absence.
If this child was suffering from a clinically significant bowel disorder would you expect this sort of information, apparently being given to be handed out “to whom it may concern” to be dictated by Dr Wakefield a researcher?
A No, certainly not, and I think the other point to make is that Professor Walker-Smith had already confirmed in correspondence that this patient did not have any evidence of bowel inflammation.
Q Then later on there is a letter from the GP, in January 1999, to Professor Walker-Smith because the mother is concerned about the child suffering from fatigue and pallor and bloody diarrhoea, and if we look at page 47 of the Royal Free records we see that child 7 was seen again on 29 January 1999 in the outpatient clinic because there was an episode of abdominal pain, diarrhoea, mucus and some intermittent blood. This has rather reduced in severity and the mother was concerned about his colour.
“As you know, he is taking Olsalazine and at present is not on any therapy for constipation.”
So it appears there had been a re-prescription.
“He is passing up to three stools a day which vary in consistency from hard to diarrhoea.”
Professor Walker-Smith says:
“On examination I can see that he has a slightly lemon-yellow colour but I am interested to see that he does not have elevated bilirubin from your investigations. …. Some local reddening of the anus. It was also important to repeat … his CRP, liver function test and full blood count. Should these abnormal, it may be helpful to do a repeat colonoscopy. Otherwise I would continue on his present medications for the time being.
Dr Wakefield will be in touch in due course with the family about the investigations.”
If that is a reference to the investigations which Professor Walker-Smith thinks it might be important to repeat, particularly CRP, liver function test and full blood count with the possibility of a repeat colonoscopy, can you understand, Professor Booth, why Dr Wakefield would need to be in touch with the family in relation to those investigations?
A No, I cannot. I think the plan of the investigations as set out by Professor Walker-Smith in the light of those symptoms is entirely reasonable.
A But I cannot, I am afraid, understand why Dr Wakefield would need to be involved.
Q And if he is involved, does that point, whatever Professor Walker-Smith’s clinical view may have been, if an involvement is made then with Dr Wakefield about the investigations, what does that suggest to you that the purpose of them is?
A It would suggest that there is still some lingering research interest in this patient.
Q That continues, because the child is also being seen at the local hospital. If we go on, please, in the Royal Free records, to page 45, this is the clinical discharge summary from the XXX Hospital for sick children. This little boy was brought in to casualty by ambulance following a seizure at home. He had been unwell for a week, and there are various details which I do not think we need trouble with are set out. We see at the bottom of the letter:
“We note that in the past [Child 7]”
and I think that is “has previous suffered” –
“from febrile convulsions and felt that the most likely diagnosis in this case is a febrile convulsion secondary to some unidentified viral illness. I have discussed [Child 7]’s case with Dr Wakefield at the Royal Free Hospital and he has requested that for any future admissions that [Child 7] may have, it would be helpful for him and his Research Team if blood were taken for measles serology along with other tests. We ourselves have not made any formal arrangement to follow [Child 7] up but thank you for continuing his care.”
That was a letter from an SHO to the GP. You have said that there is a lingering research interest – a phrase I think you have used in this case. Is that born out by that request, Professor Booth?
A Yes. This would seem to confirm did have a continuing research interest in this patient.
Q Do you have any comments – and we will be returning to this whole subject - difficulties in obtaining blood for research purposes in children? Later on when you are giving your evidence, do you have any comments about Dr Wakefield apparently asking an SHO, that blood should be taken for measles serology?
A I think he is saying, if it could be taken along with other tests. He is not suggesting that the patient should be bled specifically.
Q No, no.
A I think in the context of a continuing research involvement it would not be unreasonable, if someone was taking blood, to take a bit more for some other investigations.
Q Can you see any reason for it, other than a research reason?
Q Just to complete the story, can we go to page 42, which is a letter from the SpR in gastroenterology. By now it is 2000. It is a letter to Dr Wakefield. There is an episode of a possibly allergic reaction. He is currently on Olsalazine and liquid paraffin although he is unable to take the liquid paraffin. His mother has tried him on lactulose. He gets abdominal pain from time to time and still remains constipated. On examination, still has constipation palpable.
“I have in the meantime suggested to this mum that we may try and stop the Olsalazine and he has never had any obvious inflammation in his colon histologically and mum had not noticed much change after starting the Olsalazine. Should he however have any deterioration after stopping it, I suggested that she re-start this again.”
Then I think I can just summarise it by saying that thereafter the child is seen in outpatient appointments by various people at the gastroenterology department at the Royal Free on and off until 2004. In conclusion on this child, Professor Booth, you have told us that it is your view that the programme of investigations were consistent with a research purpose. Bearing in mind the contents of the research protocol, do you regard his inclusion as appropriate, given that Dr Berelowitz’s assessment was undertaken after the investigations were carried out and was not consistent with a diagnosis of disintegrative disorder?
A Yes. It would not be appropriate to include this patient as he does not fulfil the key inclusion criterion. In fact, I think the GP referral letter mentioned that it was felt that this patient did not have autism.
Q Thank you. Sir, that is all I have to ask you about [Child 7]. Could you now find your report on [Child 10], please, and I will invite the Panel to find the Royal Free Hospital records, volumes 1 and 2. They are also going to need the Health Visitors’ records. Could we please go to volume 1, to the referral circumstances, please. It is page 35. This is a letter from the GP, Dr Hopkins.
“Dear Professor Walker-Smith
Thank you for seeing this unfortunate 3½ year old boy who has been extensively investigated by our local paediatricians.”
He then sets out his behavioural circumstances. There is a
“… history of loss of acquired skills. This appeared to follow on from a viral-type illness which [he] caught whilst visiting his grand-parents … This was apparently accompanied by a rash and thought to be a measles-type illness. Unfortunate he was not seen by any doctor from this practice and we have no documentation on this.
He had been given the MMR vaccine on 21.2.94.”
Then he says that investigations have been performed by the community paediatrician locally, and he a raised measles antibody. He had recurrent ear infections.
“No actual diagnosis has been given for [Child 10]’s condition but the most recent report states ‘severe speech and language disorder with some autistic features’ – 2.9.96.
[Mr 10] – who holds a PhD – has heard of your work and is keen for [Child 10] to be assessed by yourself.
The situation is obviously much more complex than I am able to outline in a brief introductory letter and 10 has been seen by a Consultant Paediatric Neurologist and a Principal Clinical Psychologist in addition to the Community Paediatrician and ENT surgeon.
However, the situation is so difficult and complex that I'll be grateful for any help you can give.”
Then he offers to forward copies of any letters in his possession. He says,
“… of course you could liaise with the Consultants directly.”
Indeed he did correspondence and quite a lot of it is between pages 36-56 of the Royal Free hospital records. I am not going to take you through it all, save to say – and I am sure someone will tell me if I am wrong – but I think it is the case that they deal in detail with his behavioural circumstances, his involvement with an ear, nose and throat surgeon in relation to his hearing, but there are not references to gastrointestinal problems. Going back to the referral letter on page 35, and I have asked you this in relation to other cases, given this was a referral to a department of paediatric gastroenterology with a detailed letter, is there anything striking about it to you?
A It is a very good referral letter, in that it is very detailed, but it does not mention any gastrointestinal symptoms.
Q Would you expect some query to be raised about that from the consultant to whom the referral is made?
A Yes. You would wonder why you had received this referral.
Q In fact, Professor Walker-Smith wrote to the GP. It is in the GP records at page 80, if anyone wishes to look at it, but I am not going to take you to it. It simply arranges an outpatient appointment. Then we have the notes of the outpatient clinic that ensued. That is in the Royal Free records, Volume 1 at page 17, relevant to the gastrointestinal symptoms. Can we go to the bottom of the page? We see:
“Screams, clutches stomach, falls to the floor – present for several months. Not clear related to food.”
And I think it then says,
“Limits his food.”
Then over to the next page:
“Has episodes of watery diarrhoea. Up to 5 episodes a day. Stools more normal if…”
And then a word we cannot read.
“… no vomiting.”
And he is then examined, and on examination nothing abnormal detected to his abdomen. Then the history is set out clearly by Professor Walker-Smith to the GP at page 32, Professor Booth. It is dated 11 November 1996.
“Dear Dr Hopkins
Thank you so much for referring this very difficult problem with [Child 10]’s history of loss of acquired skills, and somewhat autistic features which have improved. From a gastrointestinal point of view it is interesting that he has intermittent episodes of watery diarrhoea and has episodes of screaming when he clutches his abdomen which could be related to abdominal pain. The parents are keen that I should investigate him for possible gastrointestinal disease, it is very interesting that he has a high measles antibody and I think that this needs to be taken into account with the possible relationship of measles immunisation and inflammatory bowel disease. I am therefore arranging for him to come in to have a colonoscopy on Sunday 12th January, that was the earliest date that suited the parents.”
That letter was copied to Dr Wakefield. In this case, there is not any reference, either in the outpatient clinic notes or in the subsequent letter to the general practitioner, of a plan to undertake blood tests as a screening exercise to examine for inflammatory markers. What is your view as to whether that would have been an appropriate course with this child, given these symptoms?
A I do not think with these symptoms that there is an overriding indication to carry out a colonoscopy as the first, and apparently, only investigation, without any other investigations as well.
Q So what is it in your view should have been done in this case as preliminary investigations?
A I think if you are thinking about inflammatory bowel disease, as is clear from Professor Walker-Smith’s letter, it would have been helpful to have done some screening investigations. The other issue is this patient, from the history, sounds as if he is getting severe colic and one would want to carry out some investigations to see if you could determine what the cause of those was, perhaps before doing a colonoscopy, of which there would be a number of possible investigations – the causes, and a number of possible investigations.
Q Given the terms of Professor Walker-Smith’s letter that the parents were keen for the child to be investigated, and drawing attention in particular to the issue as to the high measles antibody, and whether that could be connected with immunisation, what is your view, again, as to whether this is a clinical or research investigation ?
A I think with the information available, it is difficult. It sounds as if the parents had read about this hypothesis and wanted to have their child investigated. But I think at this stage it is not clear whether this patient is being investigated for clinical or for research reasons.
Q Then chronologically, we know that the next thing which happened was that there was a referral by Dr Davis, who was the consultant community paediatrician, to a Dr Huw Jenkins, who is a consultant paediatric gastroenterologist
Is that correct?
A That is right, yes.
Q Is he a clinician you know of, Professor Booth?
A Yes. Very well.
Q Is he an experienced consultant in paediatric gastroenterology?
Q If we could just have a look at the letter. That is in the health visitor records at page 32. This is a letter from the consultant community paediatrician to Dr Jenkins:
“I gather this child’s parents have spoken to you on the phone. He has profound speech delay with autistic features. He had a severe measles like illness … and his problems have all begun since then. Before that he was said to be a very normal child. He has chronic but intermittent diarrhoea. I don’t think he has symptoms of malabsorption but he has been seen at the Royal Free Hospital fairly recently and they were planning to do a colonoscopy. However, his parents would much prefer to have any necessary treatment in XXX and are very keen to discuss this with you.
They are also actively exploring the possibility of a link between measles vaccine or illness and their son’s problems and they are aware of some research going on at the Royal Free which involves giving children intravenous haemoglobin and they would like to discuss this with you, although obviously I am rather sceptical about this but you may be more aware of what the current research activities are.”
And he asks for an appointment. Dr Davis also wrote to Professor Walker-Smith. That is in the Royal Free Hospital records, volume 1, at page 31:
“I gather that [Child 10] is coming to see you next week for investigations in connection with his severe speech and language disorder and possible food intolerances. His father has asked me to forward [Child 10’s] MRI scan films which were reported as normal … I thought you might also be interested to know that we did some blood tests in August last year which were reported as normal …
Then he sets out the results. Would you agree that they were normal, Professor Booth?
A Yes, I would.
Q The letter goes on:
“[Child 10] still has a total lack of speech and some autistic features although not enough to amount to a diagnosis of Autism per se. He has never presented as having an overt gastroenterological problem, although his parents in retrospect do report some loose motions. Interestingly recently [he] has been refusing to eat milk products or wheat products and his parents have noticed some improvement in his social skills. I would be interested to know your findings and look forward to the outcome of the research in due course.”
That is Dr Davis to Professor Walker-Smith. Then we follow on to the admission of the child. He was admitted on 16 February and discharged on the 19th. We now need to go to volume 2 of the Royal Free records, please. At page 11, at the top of the page, we see:
“Admitted for [investigation] of disintegrative disorder/measles/ [inflammatory bowel disease]”
Then we see:
“[Complaining of] learning difficulties
? abdominal pain
- occasional diarrhoea”
Then, “Parents contacted Andy Wakefield”. Then going down to the history:
“Well until [16 months] → had MMR at [1 year]
June 1994 at [16 months] had measles infection [diagnosed] by GP … who thought it as German measles.”
We see it lasted for four weeks and then he seemed to recover. Then:
“No bowel problem”
It then says there was a history of deterioration and it sets out how, over the next few months, he seemed to gradually disappear and began to loose eye contact. He had had some gradual improvement since August 1995. Then going on to page 12:
“Summer ’96 → seemed to deteriorate → pulling up knees, clutching abdomen → seemed to stop eating dairy products → improved.”
Underneath that, we see:
“Bowels → no bowel control”
Then under the heading gastrointestinal tract”:
“[Bowel opening] occasionally watery
occasionally has to strain at stool
[opens bowel two to six times a day]. No blood, no mucus”.
Then an abdominal pain which the mother connects to a particular snack. Going on to the next page, investigations he has already had:
“MRI → normal
EEC → normal
Blood tests → normal
And it then says “was high”. That clerking note overall, Professor Booth, taking what has gone before it and your observations then and also the reasons given for the admission on the first page of it, does it seem to you that the admission was for clinical or research reasons?
A The reason for the admission is given as “investigation of disintegrative disorder, measles and IBD”, so that immediately makes one think that this was a research driven investigation. There are comments in the notes about the gastrointestinal symptoms having been mild and the symptoms that this patient had in the clerking would not make you think that a colonoscopy was the first investigation to perform without any other information being available.
Q If we go to the endoscopy clerking note to see the reason for that procedure, just carrying on from the comments you have just made, that is at page 16 and it says:
“High measles antibody. Autistic. Clutches abdomen
? inflammatory bowel disease”
Then a reference to dietary exclusions improving the position. Then under “Fitness for General Anaesthetic”:
“Some autistic tendencies after developing measles post MMR. Full investigations in XXX.”
General speaking, a high measles antibody, would you expect that to be relevant as a reason for the procedure of colonoscopy?
A I have done a lot of colonoscopies, but I have never measured measles antibodies.
Q In normal circumstances – and this is a clinical investigation – was there sufficient evidence in your view on what we have just looked at for there to be a suspicion of inflammatory bowel disease such that a colonoscopy was immediately indicated?
A No. The symptoms are certainly not first rank symptoms which would make you think that this patient had a colitis and there is also the evidence supplied by the referring paediatrician in XXX that the inflammatory indices were normal.
MS SMITH: Sir, I am going to turn on to the results of the colonoscopy and the histology. I see it is just before one, so if this were an appropriate moment for you, I think it would be appropriate for me, rather than turning to the next thing.
THE CHAIRMAN: Certainly. Thank you. We will now adjourn for the lunch break and resume at 1.55. Once again, Professor Booth, do not discuss this case.
THE CHAIRMAN: Good afternoon, everybody. Yes, Ms Smith?
MS SMITH: Thank you, sir. Going on, if we may, Professor Booth, with Child 10. You will recall that just before the lunch adjournment we talked about the endoscopy clerking sheet and the measles antibody. Just to complete that, there are two consent forms, which I will not take you to, in a form we are now used to: a consent form for colonoscopy and lumbar puncture in the normal clinical form and a consent form for research biopsies. Then on the following day, the colonoscopy was indeed undertaken. That is at page 45 of the Royal Free Hospital records, volume 2. It says:
“This colonoscopy was definitely abnormal, in probably a more striking example of the pattern seen in the cohort of the autistic children. The rectum showed definite mild abnormality, with a slight granular mucosa and abnormal vascular pattern. Prominent lymphoid follicles could be seen throughout the colon, with no other mucosal abnormality. The caecum showed an erythematous, granular mucosa around a swollen ileo-caecal valve, while the terminal ileum showed minor inflammatory change and striking lymphoid hyperplasia distally.
I suspect that the biopsies will show unequivocal abnormality!”
This is one of the procedures which was undertaken by Professor Murch. Do the comments you have made in relation to the responsibility of the person carrying out the colonoscopy apply in this case?
Q Blood was taken on the same day and in fact postdate the colonoscopy. The results are set out at pages 50 and 53 of the records, but I think the easiest form of looking at them is in the discharge summary, which is page 39. I will revert to the discharge summary for other reasons later, but if we just look at the results of those blood tests, Professor Booth, can you confirm what they reveal?
A I think the ones of relevance at this stage are down towards the bottom of the list: CRP, haemoglobin and platelets are normal.
Q Bearing in mind the information which was available to the Royal Free, that is the referral documentation and the presentation in outpatients which we know was abdominal pain, not apparently of long-standing, but interspersed with constipation and diarrhoea, was the colonoscopy in your view clinically indicated in this case?
A No, not as a first line investigation.
Q As far as the results of the inflammatory indices are concerned, if they had been available prior to the colonoscopy rather than after it, would that have assisted in making the decision, at least to delay the colonoscopy?
A It may well have done if they had been clearly abnormal.
Q Do you think that they should have been carried out before this decision was made?
A I think in the absence of an obvious indication for doing a colonoscopy, it would be usual and wise to check the inflammatory indices and possibly some other investigations first before embarking on a colonoscopy.
Q Are you critical of the failure to do that in the circumstances of this child?
A Yes. I do not think it would be usual clinical practice in a patient with those symptoms to go straight for a colonoscopy.
Q Returning to the chronology, if we go to page 14 in the same bundle, please, we see on 17 February a ward round with Professor Walker-Smith, which says:
“colonoscopy – mild proctitis
[terminal ileum] → lymphonodular hyperplasia”
“→ Could have [barium meal and follow through] in XXX
→ letter to Huw Jenkins”
On the same day we know this child also had a lumbar puncture, because – again, I will not take you to it – the Royal Free Hospital records at pages 50 and 54 show the cerebrospinal fluid results for that day. Then there is a clinical note by Dr Berelowitz on page 18. The child was seen by Dr Berelowitz on the 18th:
“Seen by child psychiatrist
Detailed report to follow”
Then, as I have already mentioned, he is discharged ultimately on 19 February. Following that, there is indeed a letter from Dr Berelowitz to Professor Walker-Smith. That is in the Royal Free Hospital notes, volume 1, please, at page 28. That is a letter which was sent by Dr Berelowitz to Professor Walker-Smith this time, but copied to Dr Wakefield. It says in the first sentence:
“I saw [Child 10] on Malcolm Ward … In fact I saw [Child 10’s] father only as [Child 10] was sleeping, and father said mother would not wish to participate in a research interview.”
Then it sets out the details. In the second paragraph on the second page, we see:
“He had diarrhoea and possible abdominal pain, but this is no longer significant.
You will see from the above account that [Child 10] has certain features of autism, and certain of the features of disintegrative disorder. However, in fact he does not meet the criteria for either of these two conditions.”
Then he sets out why and he says:
“ … a clinical cause, apart from the bowel and bladder problems does not really fit with disintegrative disorder. Furthermore it is possible that he does not truly lack bowel and bladder control, but has merely not yet been successfully toilet trained. Only time will tell.”
He then sets out his concerns that the mother would apparently prefer the worse diagnosis of disintegrative disorder and he says:
“I must say that I thought the most likely diagnosis was in fact an encephalitic episode, which led to some low grade generalised brain damage. You will see above that in the acute episode he had fever, rash, vomiting and a low level of consciousness … ”
He mentions about the father regretting not taking him to hospital. So that was Dr Berelowitz’s view. As I say, that letter was copied to Dr Wakefield and addressed to Professor Walker-Smith.
Dr Berelowitz refers there to the fact that anyway so far as the psychiatric assessment was concerned that he was regarding it as a research interview, Professor Booth, but is that consistent with your overall view as to the nature of this admission?
A Yes, it is. The admission clerking referred to admission for disintegrative disorder, measles, IBD study and I think that is entirely consistent with the information that Dr Berelowitz provides in his letter.
Q Just so we are clear: if you have a situation where you had the clinical admission of a child for gastrointestinal symptoms and the investigation of those gastrointestinal symptoms who happened also to have a behavioural disorder, in the context of that clinical admission would you expect any kind of neuropsychiatric assessment to be carried out?
A It would depend I think on what had been carried out on the patient before. If this was new information that was coming to light or you had been referred a patient with gastrointestinal problems and the referring doctor had said, “It would be very helpful while the patient is in your hospital if they could see X and ask them to give me some information about what they think is going on” that would not be at all unusual.
Q But if you have a situation where there is a diagnosis in respect of the child and they are coming for a gastrointestinal investigation and it is clinical, would you have any reason to revisit that diagnosis?
Q Turning to the histology. You will remember we looked at the colonoscopy and you will recall there were remarks made of the lymphoid nodular hyperplasia there and the fact that Professor Murch thought the biopsies would show an unequivocal abnormality, there is a histology report by Professor Jarmulowicz at page 51 in volume 2. We see the report at that stage, although there was a change in relation to this, was that there was no significant histological abnormality but then there is a handwritten description of the histology in the same volume of records at page 17. That says: “Colonic biopsies – abnormal crypt architecture and mild …” – I cannot read the next word, can you? Is it distortion?
Q Distribution or distortion.
MS SMITH: “Of chronic inflammatory cells …” Very mild distribution of chronic inflammatory cells.
MR HOPKINS: Sir, there is a better copy in RF1, page 15.
MS SMITH: That is very kind, thank you. I am told our copy is worse:
“Focal abnormalities. Observed goblet cells …”
A I think that is decreased goblet cells.
Q “Decreased goblet cells. Focal abnormalities of the epithelium …” - sorry, both my copies are so bad I cannot get there.
MR MILLER: “ie tufty.”
MS SMITH: Tufty? I am told “ie tufty” I am told by Mr Miller, “nuclear debris in ---
A Sub-epithelial deposits.
Q Thank you, and then the words, “enough chronic inflammation to merit treatment with Sulphasalazine”, so that is the observation that was made in relation to possible treatment. Then we have Dr Davies’s list for the histology meeting, and that is in volume 1 at page 59aa. We see child 10’s name is the third one down and it says “nothing abnormal detected” by it but then at the bottom of the page there is a reference in the second of the two manuscript notes to child 10 and it says that there should be a review and “? Supplemental report” because “? Surface damage.”
A Surface change I think that probably is.
Q There was indeed a supplemental report and that is at 59a. We see there the note:
“These biopsies have been reviewed following a clinicopathological meeting. The ileo biopsy shows confluent lymphoid aggregates within otherwise unremarkable small intestine. The large bowel biopsies show a very subtle scattering of chronic inflammatory cells within the lamina propria. The superficial lamina propria contains focal nuclear debris and the surface epithelium appears slight degenerate. No active inflammation is seen. More levels have been cut and no granulomas have been identified.”
Then the comment “Minor abnormalities ? significance”.
Returning to the chronology and following on from that, in the Royal Free records volume 2 at page 38 we have the discharge summary:
“[Child 10] was admitted for other investigations of his bowel symptoms in association with possible disintegrative neurological disorder and possible association with measles vaccination.”
It gives a history of learning difficulties and abdominal pain with occasional diarrhoea, and noted that there was an elevated measles antibody: microscopic colonic inflammation with lymphoid nodular hyperplasia and then it sets out the history of his bowel problems. We see also the history of the previous investigations under Dr Davies the community paediatrician (at the top of page 39). He had had an MRI, EEG and various blood tests all reported as normal: “Nevertheless, a measles antibody titre was noted to be quite elevated.”
A colonoscopy was performed, and the description given of that, and then:
“Biopsies were taken during this procedure and demonstrated normal crypt architecture but with mild, increased distribution of chronic inflammatory cells throughout the colon. There were also decreased goblet cells and focal abnormalities of the epithelium.”
Then the blood tests are set out, and you have already told us the inflammatory indices taken after the colonoscopy were normal. He was reviewed by the child psychiatrists and then:
“In view of the definite inflammatory changes noted in his colonic biopsy we feel it would be appropriate [to treat] with anti-inflammatory medication and therefore will recommend treatment with Sulphasalazine … which we would be grateful if you would prescribe this.”
As far as the histological description ultimately given in the discharge letter, that accords with the handwritten description that I have taken you to, which was the revised view.
Q In the light of that description having been recorded in the records, in other words the reasons for the re-description of the histology, I think it is right that you concluded that, as there was an explanation for the histological findings, that was what you would expect if there had been a change of this kind noted?
A Yes, it is absolutely clear what the process has been and there is a signed alteration to the original report.
Q Is that what you would expect in fact?
A Yes, if you are making substantial changes to the histopathology, or at the very least something written in the clinical notes to say that it has been discussed and what the basis is for coming to a different conclusion to the published report from the lab.
Q Turning to the follow-up, if we can look at the Royal Free records at page, this is the letter that was subsequently sent by Dr Casson, the registrar at the Royal Free, to Dr Jenkins the paediatric gastroenterologist, dated 15 April 1997:
“Dear Dr Jenkins,
Professor Walker-Smith would be extremely grateful for your assistance in managing this child. As you know, we have now seen several children with a syndrome comprising a neurological disintegrative disorder (part of the autistic spectrum) and bowel problems. In [child 10] we noted similar colonoscopic and histological findings to several of the other children. In view of this he was started on Salazopyrin … Nevertheless, mum has not noticed a significant improvement and remains convinced that there may be an element of reaction to certain foods. On discussion with her it is also possible that constipation has a role to play in his symptoms.”
A discharge summary is enclosed and the letter asks whether the child could be seen in the outpatient department in XXX as it is obviously difficult for them to be seen in London.
Thereafter, there is some continuing correspondence with Dr Casson. That correspondence goes on for some time about the prescription and who is going to monitor. The letter dated 2 July in volume 2 of the Royal Free records at page see at page 33, a letter to Dr Huw Jenkins from Professor Walker-Smith:
This is another child within the group relating symptoms and measles vaccination.
I would be grateful if you would take over his care …”
He asks for Dr Davis in histopathology to send sections and a copy of the discharge summary.
If we then go to the GP records, page 57. This is Dr Jenkins writing back to the consultant community paediatrician, the biopsies having been sent from the Royal Free as Professor Walker-Smith had promised:
“I have now had a chance to review [child 10]’s intestinal biopsies kindly sent down from the Royal Free Hospital and although there are lymphoid follicles present in the small intestine these are often regarded as a normal finding, and certainly our pathologists here would suggest that the colonic biopsies were within normal limits and certainly they do not feel he has good evidence of gut inflammation on the biopsies.
We will be seeing [child 10] again in October but I see no reason to start Sulphasalazine or any other derivative as a treatment for possible colitis/inflammatory bowel disease.”
He writes also to the consultant paediatrician at page 54. This is a letter from Dr Jenkins, dated 5 October 1998:
“I reviewed this young man … today and I think you have already had my letter about his biopsies, which were certainly felt by our pathologists to be within normal limits. His major g-i problem is constipation and at present he is taking Lactulose and the situation is moderately manageable.
I have had a long discussion with mum today regarding the need to continue the Salazopyrin and she is keen to try a period without this to see if it makes any difference to his symptoms.”
There is then reference to the mother’s wish to explore a number of other avenues in relation to his condition.
Thereafter there is some conflicting correspondence with the mother, the sometimes being on Sulphasalazine and sometimes on Salazopyrin and complaints as to his suffering from constipation. I do not think I need to take you to any more of those, save to say that it does not appear that the Royal Free was involved after that time.
Again, for the avoidance of doubt, Professor Booth, does it appear to you that those investigations undertaken during the admission to the Royal Free of this child were carried out for clinical or research reasons?
A For research reasons.
Q This is a case where Dr Berelowitz, as you know, spoke to child 10’s father, and the other investigations, including the colonoscopy had already been undertaken, and he made a conclusion as to diagnosis that the child did not fit the diagnosis for disintegrative disorder, so if this was an admission for research protocol was it one in your view which was appropriately carried out?
A No. Dr Berelowitz should have confirmed the presence or absence of a diagnosis of disintegrative disorder before the other investigations were carried out. This was a study on children with disintegrative disorder. For some reason Dr Casson refers to the diagnosis of disintegrative disorder in this patient even though it had not been substantiated.
Q I want to turn on to another matter relating to this same child, child 10, and just so you know where I am – remembering the Panel does not have your reports – you deal with it on page 69 of your overview report, and this is the issue of the transfer factor. If I may I will remind you of the factual background. If we have a look at the GP records at page 65.
This was a letter sent in August 1997 to the GP, Dr Thomas, again from Dr Davies, the Consultant Community Paediatrician. At that stage, if we look at the first paragraph, he is still on for bowel inflammation and is awaiting some new treatment with measles transfer factor. It then says his diarrhoea is much improved. That is the first reference to it. Then, if we look at the Royal Free Hospital records, volume 1. The document starts at page 178, and the page that is relevant to this matter is page 181. This document is a behaviour check list which was filled in by the child’s mother. On page 181 it says:
“But he is not as good as he has been recently. Over Christmas and New Year we felt very optimist about the apparent effect of Transfer Factor – there seemed to be such a noticeable change in [Child 10] but this week we feel pessimistic. This may be a stupid question, but is it possible that the dose now needs to be increased.”
That was the mother writing. Then the last document in the same volume, page 20, please. This is the Vaccine Damage Questionnaire filled in for the Medicines Control Agency. If we look at the middle of page 21, under “Further details of possible adverse effect”:
“c) Has any treatment been given for this possible adverse effect?
Yes. In view of the colonic inflammation [Child 10] was commenced on mesalazine. When measles virus antigen was detected in his bowel biopsy he was started on measles virus-transfer factor (details available on request).”
That document, as you see on the next page, page 22, 3 February 1998, is signed by Dr Wakefield. That is the documentation indicating that Child 10 was indeed being given this substance in February 1998. Can we remind ourselves of the other documentation related to the transfer factor? At the same time, i.e. February 1998, an application was submitted to the ethics committee in relation to the substance. That is in your bundle FTP2, Professor Booth, at page 675. This, you will recall, is the application for the trial of an open-label study of transfer factor which was submitted, as I say, at the same time in February 1998 to the chairman of the ethics committee. It is from Dr Wakefield. You will see it says:
“One child who has received this treatment on a compassionate basis appears to have made substantial improvement with any noticeable adverse effects.”
And, going into the heart of the application at page 677 we see that the objective was:
“To assess the clinical benefit of measles virus-specific transfer factor ... in children with developmental disorder and intestinal inflammation …”.
- what is now called autistic enteropathy. At page 680:
“Anecdotally, we have started one child with autistic enteropathy on … [transfer factor] on an approved compassionate basis; he has tolerated the therapy, for one month so far, without any adverse effects and according to his parents has shown definite improvement.”
Just going back to page 676, we see that the principal clinical investigators including Professor Walker-Smith and the principal scientific investigator is said to be Dr Wakefield. Subsequently, as we have heard when the previous expert, Professor Rutter, was asked questions about this, there were numerous questions made by Professor Walker-Smith as to the safety aspects of this drug, for the purposes of satisfying the ethics committee as to the trial. I, though, want to revert with you, Professor Booth, to Child 10. Firstly, with respect to the claim that the substance was given to the child as a compassionate treatment, on a compassionate basis, what do you understand that phrase to mean?
A I think you would understand that the patient who was receiving transfer factor had a severe, possibly incurable, life-threatening disorder. That would be the normal circumstances where you would provide experimental treatment on a compassionate basis.
Q If it was going to be used on that basis, would you expect to see the details in respect to matters such as the dose and the parental consent in the medical records of the child?
A Yes. The reasons for giving the drug should be very fully outlined in the clinical record. You may well include a summary of a discussion that took place with the clinical team and other people who are not directly involved with the patient, to be clear that this was an appropriate intervention – although in this case application was made in a sense to an equivalent body, because application was made to the research ethical committee. But you would expect to see the reasons for giving the drug. You would expect to see a summary of the discussion that had taken place with the parents about why the patient was being given the drug, and you probably would get a signed consent form from the parents to show that that had been undertaken and they understood why this agent was being offered.
Q As far as the ethics committee application is concerned that, of course, is being made in relation to a trial of the drug on a number of patients, and is after Child 10 is already on the substance?
A Yes, that is right.
Q If the ethics committee was being consulted, would you expect that to be before rather than after the event?
A I think if you are planning to give this to a number of patients, you would want to get the ethics committee.
Q Of course, yes.
A If you feel there was really urgent, life-threatening reason to give a drug that had not been fully evaluated to a patient on a compassionate basis, then it would not be appropriate to submit that to a research ethical committee. The need would be too urgent.
Q You cannot, I think it is right, comment on transfer factor itself as a substance? It is not something on which you ---
A I have no knowledge about its use, no.
Q But you have looked at all these children in the series of the 11 of the 12 Lancet children. Is there anything that you could see gastrointestinally which singles out [Child 10] for treatment that others did not have on a compassionate basis?
Q And can you see any reason why he, more than any other, might require so called compassionate treatment?
Q If an innovative treatment of this kind is being given for compassionate reasons to a patient, whose responsibility is it to make that decision?
A It would be the consultant who was in overall clinical charge of that patient.
Q We know from the subsequent application in relation to this substance that Professor Walker-Smith and Dr Wakefield were principal clinical and scientific investigators, and the application refers to the fact that “we” have started one child on this treatment. Would you expect Dr Wakefield to have anything to do with the prescription of a substance for any reason, compassionate or otherwise, to a child patient?
A He might be in a position to suggest its use, but would not be in a position to take clinical responsibility for its administration.
Q And as far as the person who would take clinical responsibility for it, would they also be the one who was responsible for its entry into the records?
Q And just on the issue of advice to the parents in such circumstances, Professor Booth: if you were giving a drug for compassionate reasons which was experimental, i.e. not usually used for those indications or, I should say, substance, perhaps, rather than a drug, would it be important for the parents to understand that?
A That it was being used experimentally?
Q Thank you, Professor Booth; that is all I have to ask you about [Child 10]. I am just trying to decide where I go next. Sir, that concludes The Lancet children, and the last child on which Professor Booth is going to talk to you before he goes on to more general matters is Child JS. I do not know whether you would like to start JS, and then have a break, or break and then to JS.
THE CHAIRMAN: We would be happy to start with JS.
MS SMITH: If no one else has any strong views, I will start it. Perhaps we can break at 3.00.
THE LEGAL ASSESSOR: Where do I find reference to Child JS in the statement?
MS SMITH: I do not know if you have a bundle with the same pagination as I have, sir. It is on page 74, and it is a letter dated 15 May 2007. It is 11 May – I am sorry.
THE LEGAL ASSESSOR: I do not have that.
MS SMITH: You do not have it?
THE LEGAL ASSESSOR: No, my bundle is very different from yours, which is why it is very hard for me to follow most of this evidence.
MS SMITH: I do apologise. Perhaps we could identify it for you in your bundle. Would that be helpful?
THE LEGAL ASSESSOR: My bundle has dividers.
MS SMITH: Yes, but the report on this is in the form of a letter, which is dated 11 May and is in my bundle after the dividers, and after a long overview report. I think maybe we should have the break now, sir, so we can sort it out. My friends are suggesting it, and it is obviously more sensible.
THE CHAIRMAN: I agree with that.
MS SMITH: I am sorry; I should have thought of that myself.
THE CHAIRMAN: I am sure it would be more sensible.
MS SMITH: We will sort this out.
THE CHAIRMAN: We will now break and resume at five minutes past three.
THE CHAIRMAN: Good afternoon, again. I hope the difficulty that you had has been resolved?
MS SMITH: Yes, I hope so, sir.
THE CHAIRMAN: Are we now starting with JS?
MS SMITH: Before we go on to that, I just want to revert, if I may, for a minute or two to Patient 10, Professor Booth. This is in relation to the administration of the transfer factor. I asked you whether you would expect to see a record of the fact, and the prescription of the transfer factor, and the dose that was given and the record of any discussion of the matter with the parents. You said that you would have expected that to be reported in the clinical records. I think that I did not go on to ask you if you were actually able to find any indication, save the very brief references that I have taken you to, of such a record in the clinical records of Child 10?
A No. The rather oblique references that were touched on, but I could not find any further statement in the main body of the notes, no.
Q As well as those matters, the dose and the discussion with the parents, we have heard from the GP, that he would have expected to be informed if the child were on a substance of this kind, and that he was not so informed. Would that accord? And that he was not so informed? Would that accord with your view from the tertiary angle of that?
A Yes. I think it is absolutely crucial that general practitioners are aware of what medication patients are on because they are responsible for the care of the patient on a day to day basis.
Q You said that as far as you were concerned, that you would expect the clinician who has responsibility for the child to have the responsibility for the prescription of any experimental substance, and I asked you whether you would expect Dr Wakefield, as a researcher, to have such an involvement. You said you would not. Given Dr Wakefield’s lack of paediatric qualifications, as we have already discussed, if it is the case that he did have an involvement in this prescription – and we know there is a reference to “we” having prescribed this treatment – if he did have such involvement, should he have had any involvement in prescribing this treatment for Child 10?
A No. He should not have had any involvement in the prescription, as I think I said. He may well have made suggestions about its use, but his involvement would end there.
Q When you say it would end there, do you mean it should end there?
A Should end there, yes.
Q Could I now ask you to turn to JS, please? Sir, as far as the Panel is concerned, you are going to need the GP records, the Royal Free records and the local hospital records. Professor Booth, before we turn to this patient, I just want to remind the Panel of the circumstances, because it is running straight on from the other children we have looked at and I do not want there to be any confusion. I know you are aware of this, but the Panel will recall that the charges in respect of this child apply only to Professor Walker-Smith and it should be remembered that this child is not one of ‘The Lancet 12’. This is the child you have heard evidence about from Dr Kirrage, who was employed by the local health authority and dealt with the ECR referral issues, and from Dr Mills, who you will remember was the consultant community paediatrician who was most involved in JS’s care and the question of whether he should be appropriately referred to the Royal Free. I am going to take you first of all to the correspondence which sets out the referral process, Professor Booth, and then on to the admission and the investigations, in particular the colonoscopy and ask you for you views on that evidence.
This child was also an autistic child of a sort: he had a diagnosis of atypical autism made in February 1995. I do not have to take you to the reference for that; if the Panel wishes to see it, is it in the GP records at page 110. Primarily he was in the care of the consultant community paediatrician, Dr Mills, rather than his GP. The first letter I would like you to look at is in the local hospital records at page 117. This is a letter, you will recall, from Dr Mills to Dr Wakefield, but it arose out of communications which had already occurred between the parents and Dr Wakefield. It is dated 29 April 1996:
“I understand that you have recently spoken to the Mother of this 4 year old boy …
You suggested to her on the telephone that a referral to Professor Walker-Smith may be appropriate and Mrs JS has contacted me asking if I would make a referral.
I have been involved with [him] for several years. He presents as a child with classical autism and his language development and social interaction is severely impaired … In addition, he has mild diarrhoea which has not really been a clinical problem. There have been no problems with growth or weight gain.
The family date [his] problems to happening after MMR vaccine at the age of 18 months and they are convinced that this is the etiology of his autism. There certainly seems to have been several linked reports in the literature of association with MMR with other children, but this is commonly the case in conditions where we do not have a clear etiology and 95% of children in the UK receive MMR vaccine anyway.
Mother has asked me to make a referral to your team. Could you let me know what you would be able to offer [JS] and the family?
I am quite happy to be open minded about unsubstantiated causes and possible further treatments, but I am not keen on sanctioning detailed investigations unless there seems to be some logic behind them.”
That was a first query for information and the first indication of the gastrointestinal problems. Does the statement that the diarrhoea was mild and had not, as far as the consultant paediatrician was concerned, been a clinical problem have any significance? How would you describe the severity or otherwise of that description?
A He says it is mild. Often, with more severe problems with diarrhoea, there are problems with growth and/or weight gain. It is consistent with it being a mild problem and he says it has not really been a clinical problem.
Q When a doctor says it is not a clinical problem, what do they mean by that?
A Certainly not something that would need referral to a tertiary specialist, for example.
Q We know that in fact the mother of JS had written directly to Dr Wakefield as well. That was on 16 April 1996. That letter is in the Royal Free Hospital records at page 79. She sent Dr Wakefield a long statement about this child and the record of vaccination and the subsequent health problems. If you look at page 80, you will see the covering letter:
“Dear Dr Wakefield
Thank you for your telephone call last week. I enclose a record of [JS’s] development and regression following the MMR vaccine.
Please let me know if you would like any other information.”
Then she says:
“P.S. If you know of a neurologist, or anyone else that you think could help please would you let me know – as I want to try anything possible to have our son back.”
Then if you go on to page 81, you will see the rest of the statement. It is a very detailed statement about this child’s development in every way, but it contains, as far as we could find, no reference to any gut or intestinal symptoms. Does that in your view add substance to the view that Dr Mills had described, namely, that gastrointestinal symptoms were not of clinical significance?
A Yes, very much so.
Q As we see, it goes from page 81 through to page 92, with a great many details as to behaviour. The next thing is a letter from Dr Mills to the GP and that is in the local hospital records at page 114. It lists the problems as severe impairment of language development and social interactions with autistic features, possible hearing loss and increasing behavioural difficulties. Dr Mills said he has seen the child, who was obviously an extremely difficult child for the family and others to manage, he was having B6 therapy, which had not been a success and then he says:
“The family remain convinced that [JS’s] problems developed after MMR vaccine and they have been in contact with several other families around the country who believe the same. They have recently tracked down a Dr Wakefield, gastroenterologist at the Royal Free Hospital in London. I have discussed the issue with Dr Wakefield myself and his team are undertaking research into measles associated chronic diarrhoea. They have, incidentally, identified several children who apparently have autism as an association and he was very keen to offer [JS] detailed gastro-enterological investigations, including a brain scan in London.
[JS] seems to have loose motions two to four times each day. At one stage they were associated with mucous, but this has now settled. There are no other symptoms which point to his GI tract and there is certainly no clinical evidence of malabsorption.”
What would be the clinical evidence of malabsorption?
A It might be the nature of the stools themselves: they might be particularly large and offensive. Often in situations where malabsorption occurs – and we are talking about malabsorption from the gut of nutrients – it is associated with impaired growth and poor weight gain as well, or evidence on blood tests that the patient has evidence of nutritional deficiency.
Q If we go on with the letter, we see Dr Mills say:
“I have to say I was rather reluctant to refer [JS] to a far flung centre for gastrological investigation and research. However, I did agree to undertake some blood tests to look for more subtle evidence of malabsorption after which we can reassess the situation. It does seem unlikely that any of this is actually going to help [JS’s] behaviour or day to day management.
I have arranged to see [JS] and his family in three months.”
Would you approve of that, the agreement to undertake blood tests?
A That seems a very reasonable approach, yes.
Q We know from the evidence that Dr Mills has given that there was a further conversation between he and the mother of JS in September 1996, when he again advised against referral. Just for the Panel’s benefit, that is in the local hospital records at page 134. Mrs JS then saw a clinical psychologist, Miss Brua, in November 1996. That is in the local hospital records at page 141. At page 142, she says:
“[Mrs JS] is desperately hoping that [JS] could have a brain scan, especially as she now sees him going backwards in his toileting.
As I said …. I am concerned at [JS’s] loss toileting skills as I do not think it is emotional nor attention-seeking …
[Mrs JS] is still in touch with Dr Wakefield at the Royal Free Hospital who is apparently saying that [JS] could come in for a week’s investigation which would include a brain scan before Christmas. This would be free of charge.”
Ms Brua says she challenged Mrs JS about dashing from one approach to another and said how little she thought a brain scan would show, but she says:
“[Mrs JS] however feels strongly that she wants to pursue the work with Dr Wakefield. I got the impression that she would do it with or without our support.
I find the situation extremely challenging. On one hand, [Mrs JS] is offered medication by Dr Tesh and rejects the idea. On the other, [she] is prepared to spend a week in hospital keeping [JS] occupied in order to have a brain scan. In the end, I feel that [JS] is probably the most difficult child in the learning disabilities service and I have not provided any real help.”
Is the sort of picture which is being painted there one you are familiar with, Professor Booth, in respect of the parents of a child with a serious disorder of this kind?
A Yes. I think parents with children with severe unexplained disorders are very vulnerable and often, as we have said, lose objectivity in what the most appropriate course of action for their child should be, which is not a criticism of them as parents, but it is a feature which places an important responsibility on paediatricians and other people looking after them, as indeed is being displayed by Dr Brua in her letter here.
Q Is that something which you expect all doctors to be conscious of?
A Yes. All paediatricians would be aware that patients’ parents in a situation where the child has a severe, unexplained disorder, are often driven into non evidence-based approaches.
Q Does that apply equally to those who are not paediatricians, but who become involved in either research or clinical work with children?
A Yes. I think one would anticipate that all doctors, whatever their background, would be aware of that as a sort of basic tenet of medical practice.
Q I will be reverting to this in the context of asking you for your comments on this case, Professor Booth, but do you think that it is actually an awareness which was exhibited by the doctors in this case, that awareness of vulnerability?
A The vulnerability of this particular mother?
Q Or mothers in general of children.
A In these cases?
A I do not find much evidence of that.
Q Reverting to the chronology, the next thing was a letter from Mrs JS to Dr Mills. That is in the local hospital records at page 144 and is dated 6 November 1996.
“Dear Dr Mills
I understand you have been talking to Betsy … ”
That is a reference to Miss Brua, the clinical psychologist whose letter I have just referred to –
“ .. about [JS] who has started to wet the bed up to three times a night.
He has also started dribbling. We are very concerned as this seems yet another step backwards.
I have this week heard from Dr Andy Wakefield who has sent me the enclosed information about Hellers disease. This sounds so much like [JS’s] history that we find it most alarming.
If this should be what is happening to [JS] then we need to find out before any more time is lost.
I would be grateful to hear from you as soon as possible.”
The enclosed information which is attached to it at page 145 onwards is the proposed clinical and scientific study. Is that a document which accords, in all essentials at least, with the document we have looked at on a number of occasions before which was sent to the ethics committee?
A Yes, it does.
Q Behind that, although there was some question raised as to where it came from, is the fact sheet in relation to the measles mumps and rubella litigation from Dawbarns, the solicitors, at page 162. After that, Dr Wakefield wrote to Professor Walker-Smith. You need now to go to the Royal Free Hospital records at page 76, dated 6 November 1996:
This is a child that I would like to be included in our study if you consider him suitable. His community paediatrician, Dr Mills, was initially enthusiastic about referring him. He now seems to have gone cold on this. Nonetheless, [JS] has been awarded legal aid who will pay for the investigations and this is [in] hand. I would be grateful if you would therefore arrange to see him as an outpatient to assess him for possible investigation in our trial.”
That letter was sent the same day as the letter from the mother to Dr Mills.
It is followed by a letter at page 75 of the Royal Free records, Professor Walker-Smith to Dr Mills of 7 November, so the next day:
“Dr Wakefield has passed on correspondence concerning [JS]. Through Dr Wakefield we have been looking at a group of children with autistic symptoms related to MMR vaccine and have found that a significant number of children have had gastrointestinal symptoms. When these have been present we have so far found endoscopic abnormalities in all five children we have investigated. I would be quite happy to see [Mr & Mrs JS] and to discuss the situation with them and to indicate what investigations might be appropriate and then to get your advice as to the right for us to proceed.”
At page 74 Professor Walker-Smith writes the same day, 7 November, to Dr Wakefield:
Many thanks for your letter. If Dr Mills and [Mr & Mrs JS] are keen for me to see [JS] I would be happy to do so. I will write to Dr Mills.”
He obviously did that at the same time.
On 15 November 1996, some 10 days later, there is a letter from Dr Mills to Professor Walker-Smith in the Royal Free records at page 73, copied to the GP:
“Dear Professor Walker-Smith, thank you for your letter concerning this boy.
The family made direct contact with Dr Wakefield themselves following information from the JABS Parent Support Group. I have spoken to Dr Wakefield and I consider that [JS] is not appropriate for the investigation schedule he recommends at present.
I understand that Dr Wakefield has been continuing to send the family information. In particular, he has been sending them information from a firm of solicitors who seem to specialise in litigation in relation to immunisation.
I agree that your research findings are very interesting, however, as [JS]’s main consultant, I do not think that your research programme is appropriate for him at present. This, of course, may change and the family may disagree with my views.
I am beginning to wonder whether you and your department are rather pressurising this family and I would request this to stop.”
Professor Walker-Smith then writes to Dr Mills in response to that, at page 72, dated 22 November, thanking him for his letter:
“I can quite understand your feeling that it may not be appropriate for us to see [JS] at the moment. However, I would be happy to hear from you again should the position change.
In relation to your last comments, I am certainly doing nothing to pressure the family to see us. In fact my department is somewhat overwhelmed by the response of parents who believe that their children have autistic and gastrointestinal symptoms following MMR. I personally had no idea that there were such large numbers of patients in the community across the country where the parents have made this association. I am sure Dr Wakefield, who is not actually a member of my own department, would also say the same.”
A copy of that letter was sent to Dr Wakefield.
Dr Wakefield also responded, and you will have to go to the local hospital records at page 191, dated 8 January 1997:
“Professor Walker-Smith has passed on a copy of your letter to me … In it you make several serious allegations. I wish to make it quite clear that I have at no stage sent this family any information from solicitors dealing in litigation in relation to immunisation. Secondly, [Mrs JS] phoned me initially and has continued to request investigation as part of our protocol. I find the accusation that we are pressurising this family grossly unfair and without any substance whatsoever. [Mrs JS], perhaps quite justifiably, has sought inclusion of her son in our investigations. It is our opinion that children with late onset autism such as [JS] have been under-investigated and their parents’ anxieties often dismissed too readily by those in charge of their care. I look forward to receiving your comments before deciding on how to proceed with this issue.”
Dr Mills wrote back, page 195 of the same bundle:
“Dear Dr Wakefield,
I am sorry you feel that the information contained in my letter of 15 November is inaccurate.
[Mrs JS] gave me a fact sheet from Dawbarns Solicitors … concerning [MMR] and [MR]. She also gave me a study proposal entitled ‘A new syndrome: disintegrated disorder and enteritis following measles/rubella vaccination?’ with yourself named as the co-ordinating investigator. [Mrs JS] told me that you had given her both these documents. It is quite possible [she] may have been confused about the origin of the documents and failed to admit that they had come from separate sources. However, I certainly was led to believe that you were the source of both documents, particularly as the Dawbarns document encourages parents to contact yourself if ‘your child has developed persistent stomach problems (including stomach pains constipation or diarrhoea) following the vaccination’. The article comments that you are looking into Crohn’s disease.
I apologise if I have incorrectly attributed the source of this document to you.
My comments concerning the fact that you may be pressuring the family are the result of the following facts.
I fully accept that the family contacted you in good faith and that you encouraged them to discuss with me the possibility of referral to your department for further investigation. I recollect that you and I have spoken on several occasions on the telephone concerning the possibility of referring [JS]. I have always been interested in your research, but have always been of the view that, given [JS]’s current clinical state, his lack of any gastrointestinal symptoms of any significance and the extensive nature of the investigations that you are recommending, your programme would not benefit [JS] at present.
As I recollect, I made this view known to you and [Mrs JS] on a number of occasions. In addition, I have asked one of my paediatric colleagues to review [JS] and she is of the same view.
In view of all these facts, I was rather surprised to receive a letter from Professor Walker-Smith on 7 November continuing to recommend referral to your department.
[JS] is an extremely difficult child to deal with clinically. He is extremely difficult to restrain in the home and school environment. Like [JS]’s parents and yourselves, we are desperate to find something that will alleviate both [his] symptoms and the family’s distress. However, on reviewing your research programme, myself and my paediatric colleagues have felt that this is not what [JS] needs at the moment.
I hope that you will now take the clinical decision of those people who are currently looking after [JS] that investigation by your department is, at present, not a pressing need. If [his] clinical situation should change in the future, or indeed if the results of your investigations indicate that [he] may benefit, then I will be happy to change my clinical advice.”
That was the response from Dr Mills. It was copied to Professor Walker-Smith, and the last letter is on page 192, which was a letter back from Dr Wakefield saying:
“Dear Dr Mills,
Thank you for your letter and comments … I appreciate your taking the trouble to respond and I now consider this matter closed.”
That was in February 1997, but we know matters did not rest there because Dr Wakefield then writes to Professor Walker-Smith in April 1997, and if you go back to the Royal Free records at page 71:
Further to our conversation, I would [be] very grateful if you would reconsider [JS] for admission and investigation. His behaviour has deteriorated to the extent that he is absconding from home and has been found wandering down the middle of the road, and on one occasion fell into a waterway. The strain on the family is absolutely enormous and I do believe that he is someone that we may be in a position to help. There is legal aid funding to pay for his investigation which I appreciate you will need to discuss with David Lee. His mother is keen for him to be investigated at your earliest convenience. If there are any problems, please do not hesitate to contact me.”
Then Professor Walker-Smith writes to Dr Mills, copied to Dr Wakefield, at page 70 of the Royal Free records in response to Dr Wakefield’s letter, this is dated 23 April:
“Dear Dr Mills,
I am writing to you again as I understand from Dr Wakefield that the family are considerably distressed concerning [JS]. We have begun to have some quite remarkable success in treating children with autism and evidence of bowel inflammation with Sulphasalazine and related drugs. I do believe it really would be helpful for us to do these investigations in [JS] or for me to at least see the child to assess the situation. I enclose a copy of our protocol and would be grateful if you would reconsider this issue once more.”
Accompanying that letter was a copy of a protocol, which is in the local hospital records, and if you go to page 199 you will see the identical letter, Professor Booth. That was a different protocol, recalling that we are now in 1997. if we go to the last page, which is 203A we see the names Andrew Wakefield and John Walker-Smith. I am not going to read all this protocol but it gives the background to the study:
“Following the publication of data demonstrating a possible link between measles virus, measles vaccination and IBD” – which was the first study in which Dr Wakefield was involved – “we have been contacted by an increasing number of parents who have described in their children features both of autistic spectrum disorder … and also symptoms suggestive of intestinal dysfunction, including pain, diarrhoea, bloating and food intolerance.”
Then it sets out the association. It quotes Professor Rutter on the next page. It sets out some of the theories associated, and then if we go to “What does this study hope to achieve?” which is on page 202:
“The purpose of this preliminary clinical study is, firstly, to adequately and appropriate investigate the gastrointestinal signs and symptoms manifested by these children”: [in bold] “investigation is merited on clinical grounds. It is our experience that these clinical features often have been ascribed to the inevitable consequences of behavioural abnormalities upon bowel function, and as a consequence the children are not necessarily being investigated adequately. It should be stressed, therefore, that the investigations are clinically indicated in all cases that are admitted for evaluation. The validity of this approach is borne out by [the finding] significant and consistent intestinal pathology.”
They say the second purpose of the study was to seek the presence and to characterise the nature of any intestinal and cerebral pathologies:
“It is our aim to investigate and institute appropriate therapeutic measures aimed at controlling the intestinal inflammation and correcting any nutritional deficiencies that may be present … Preliminary experience has shown that mesalazine or enteral nutrition may have significant benefit in some cases.
Finally, we hope the possible role of MMR will be elucidated and that further insights into the pathogenesis of regressive and classic autism will be provided.
Why should these children be investigated at the Royal Free?”
They say they are uniquely qualified to investigate this new syndrome:
“Not only has Professor Walker-Smith’s team … a large experience in diagnostic paediatric colonoscopy, but also the range of tests required to investigate … appropriately and the basic scientific investigations required for analysis of tissues ... are all sited at the Royal Free Hospital.”
Then they set out the molecular technology for detection of virus genetic material in blood, CSF and biopsy specimens.
As I say, we have to remember, Professor Booth, that this was in 1997 and it was post the children involved in The Lancet but it is the first time we have seen this document. How usual is it in your experience to see a document of this kind justifying the reasons for clinical treatment?
A As a justification for clinical treatment it would be very rare indeed, certainly if investigations are being carried out as part of a research study then it would be appropriate to acquaint the referring doctor or doctors with what was planned and the justification but for clinically indicated investigations this sort of detail would be unnecessary.
Q Reverting to the story: Dr Mills then wrote to Professor Walker-Smith and in the records that we are now in you can find that letter at page 204, and that was in May 1997, and he asks for details:
“… of your remarkable successes in treating children with autism
Please send me details of all children you have treated and the results of the successes in these children.”
He sets out what he would like to see in terms of improvements: Speech and language development: behaviour; obsessional behaviours and ease of management by the family:
“Also could you send me details as to how your detailed gastro-enterological investigations have helped these children, particularly those children who, like [JS] have a minimum of gastro-enterological symptoms.
Similarly, I would be interested to examine your evidence for the links between MMR vaccination and autism. The references that you quote are obscure and I would be grateful for copies of the information you have.”
He points out that he needs to be reassured about the contracting situation; it says:
“Your department has been very energetic in requesting [referral].
As a result of your contacts with [JS]’s family, they appear to be requesting further investigations … From the documentation that you sent me I note that you are anxious to involved [JS] in your research programme and presumably involve him in detailed follow up afterwards.”
He then refers to contact with the BBC which the mother has told him about, and he says:
“I have never sought your opinion, and I find that your correspondence puts me in a very difficult situation. I have a responsibility to ensure that [JS] has the best possible care and appropriate investigations. This responsibility also includes advising his family about inappropriate treatment and advising them sensitively about the extensive ‘alternative therapy market’. You have never met [JS] or his family or have any knowledge about his parents, their health and their wants and fears.
As this request for referral has so clearly come from yourselves, I feel that you have the responsibility to clarify the contracting situation …”
He copied that letter to the GP.
As far as the setting out of his responsibilities as consultant community paediatrician in the penultimate paragraph, would you agree with those?
A Yes, I think that is an exemplary explanation of the position of a consultant community paediatrician in this set of circumstances.
Q Then Professor Walker-Smith writes back to him and that letter is at page 206, the next page. He says what the successes are. That they are –
“… an unexpected second aspect of our study, we had expected improvement with the gastro-intestinal symptoms with the us of 5 ASA derivatives … but we had not expected the parents to tell us there had been such an improvement in behaviour.”
“… with the help of Dr Marc Berelowitz [they were] planning a further study to analyse the successes [of the work] …. But our work at the moment has been to provide a diagnostic service to determine the gastroenterological manifestations of these children. Dr Wakefield has written a paper with submission to The Lancet…”
and that, of course, is The Lancet 12 –
“which discusses the links between MMR and autism, it is under review at the moment and we are awaiting that decision.
I am afraid it is not true that my department was energetic in requesting [referral] … the pressure is coming from his parents who have heard about the success with other children. My own position in this work is entirely responsive, when I transferred from Barts to the Royal Free I was quite sceptical about the research work of Dr Andy Wakefield, but since I came here it is absolutely obvious to me that there is a large unmet need of children with autism who have a variety of gastrointestinal symptoms ranging from quite mild symptoms to quite major ones. The unexpected outcome of this research has led to us being very interested in the treatment of these drugs.”
Then he deals with the BBC.
“In relation to your final paragraph, I must again emphasise that I am reacting to parent pressure…”
He then says that the other children who come from distant authorities have been funded by ECR –
“… and the initiative must come from the general practitioner. I am myself not soliciting for patients to be referred … but I am reacting to the parents requests. I hope this clarifies the situation.”
Then the next thing is in the Royal Free Hospital records at page 65. It is a letter from Dawbarns Solicitors to Dr Wakefield.
“Have you been able to fix up an appointment for [JS] to be tested? Things are getting worse regarding his stomach pain, ‘piles’ and peri-anal irritation and he now seems to be developing joint pains.
… (his mum) is very keen to bring [JS] to the Royal Free if you can manage it.”
If that letter formed any part of the momentum for admission of this child, Professor Booth, is that a normal momentum for admission of a child for clinical investigation?
A No, it is not normal. It is extraordinary.
Q Then the next step in the story is a letter of 2 July 1997, and it is in the local hospital records at page 208. It is a letter, confusingly, “Andy”, but this time to Dr Mills, the consultant paediatrician. It is from Dr Owen, the Community Paediatrician.
I saw this child with his mother in the XXX … [Mrs S] is in touch with ? Professor ? in London re Crohn's disease associated with Autism following MMR immunisation.
School and parents tell me that [JS] whimpers prior to passing stools, the stools are mucousy and that there is what Thornton House referred to as ‘piles’ but what may be rectal prolapse visible for a short time afterwards.”
He then says he was quiet and manageable. Accompanying that letter is a manuscript note which Dr Mills wrote, and which says,
“First Evidence for Bowel Disease - ? Refer London”
He has told us that that was a note to himself to consider if his initial views re referral were wrong, and he said usually symptoms such as that would lead to a local referral but because of the history that had gone before, that he was making a note for himself to consider referral to London. In fact, matters were overtaken because that was 2 July and, on 5 July, mum writes to Dr Wakefield, copy to Dr Mills. That is at page 209.
“Dear Dr Wakefield,
I am writing to ask if you could please refer my son, [JS], for tests to see if there is any way he can be helped following the devastating damage caused by MMR … in 1992.”
He is at school, and –
“… his care assistant has noticed he seems to become very agitated before a bowel movement and that he appears to experience some pain or discomfort.
He has a history of dry – although his stools are more normal now. As he has no communication we can not tell where his discomfort lies.”
She then deals with serious behavioural problems. She says:
“I feel my doctors do not believe that [JS] has been damaged by vaccination – in spite of the fact that he was a perfectly normal baby, and a bright affection and highly verbal toddler. And in spite of the fact that the vaccine he was given was later withdrawn by the government because it carried a high risk of adverse side effects.
My husband and I feel we must explore every possibility to help our son.”
“As is it now [JS] has now future at all – other than being sedated and confined in an institution.”
She looks forward to hearing from Dr Wakefield soon. That letter was copied in by the mother to Dr Mills. As far as what is said in that letter, not generally but on the gastrointestinal symptoms, Professor Booth, namely that he seems to have become agitated before a bowel movement and had a history of diarrhoea although his stools were normal now, does that cause you to think any differently from the view that you have already expressed, namely that his bowel symptoms were minor?
A Yes. On the face of it, it would not require referral to a tertiary centre.
Q Then there are letters from Dr Kirrage who was responsible for the mother. I think I do not need to take you to that letter. It is page 211. This is the Public Health Consultant writing to the mother. He sets out his understanding of the position in relation to the MMR and autism. Then, going on to the second page, page 212,:
“Moving on to whether investigations at the Royal Free Hospital will establish the diagnosis and indicate a means of treating this, I feel that at the present time there is insufficient evidence to support this. I do acknowledge, however, that there could well be benefit from actively addressing symptoms that some children with autism have experienced. My understanding is that Dr Mills has been very exhaustive in his efforts to ensure that [JS] was not subjected to unnecessary and uncomfortable tests for gastrointestinal symptoms which he was not experiencing. I think this is entirely appropriate in Dr Mills clinical responsibility to [JS].”
“I think at the moment … there are not strong grounds to indicate referral to the Royal Free Hospital. I note from your letter … that his care assistant … has noticed that he may be experiencing discomfort before bowel movements. If this was to persist or increase in severity then I would suggest that the indications for possible referral may strengthen the balance in favour of investigation at the Royal Free. I think this is a decision that should be made by those directly involved in his care and that my role is merely to provide an objective evaluation of the indications and benefits of investigation and treatment by the study group under Professor Walker-Smith.”
In fact, the final position shortly thereafter was reached on 22 July, when Professor Walker-Smith confirmed through his secretary to the mother, private outpatient appointment.. That is how he came to be seen at the Royal Free.
I am now going on just to look at the notes in relation to the outpatient’s appointment. The notes of the appointment are on page 2 of the Royal Free records, but rather than try and decipher them in this instance, I think there is a very clear record of them in the history, which is subsequently sent to the GP. Could we therefore go on to page 107, please. On 31 July, Professor Walker-Smith said:
“I eventually saw [JS] privately particularly following a rather distressed letter I had from the child’s solicitor, outlining parental concern. You are familiar with the earlier correspondence that I have had concerning the child.”
They set out the birth history and they mention the MMR and the deterioration, and the food elimination diet was tried because of his behavioural problems.
“He was diagnosed as atypical autism … by Dr Betsy Brewer … Later he had a number of investigations by Dr Mills. … From the age of 2 years [he] had episodes of diarrhoea. However his stools are much better now and only occasionally loose. Typically he normally passes 2 large stools per day and currently his episodes of diarrhoea are quite infrequent. He does however sometimes have pain on defecation. He has never passed blood but at the age of 4 years there was some anal pathology which apparently was diagnosed as ‘piles’ from which he has subsequently settled. Currently he attends .. School aged 5½ years.”
He then says:
“On examination he is a very active child who is well nourished. Height and weight are both close to the 75th percentile. Clearly this is a child within the autistic spectrum who does have some currently rather minor gastrointestinal symptoms. There is considerable parental concern about the role of MMR in the initiation of this child’s illness. This is very difficult to b e certain about. However this is a child who would be suitable to have investigation by colonoscopy etc. and I enclose details of our protocol concerning this. I have explained the situation to the parents and I have made no definite arrangements for him to come in but I do believe that this may be something which you and the parents would like to consider that may be of value to the child.”
First of all, those gastrointestinal symptoms elicited by Professor Walker-Smith, Professor Booth, what are your comments as to the seriousness or otherwise of those?
A I think I would agree with Professor Walker-Smith’s assessment, that they are pretty mild.
Q In your view do those symptoms merit a clinical inpatient admission for colonoscopy under general anaesthetic?
Q If we look on to page 58, please, in the Royal Free records. This is Professor Walker-Smith’s letter to Dr Mills.
“I eventually saw [JS] privately at the parents’ insistence. You are familiar with the earlier correspondence I have had concerning the child.”
He then sets out all the same details and the same ultimate paragraph, but they are minor gastrointestinal symptoms with parental concern about the role of MMR. He was suitable for investigation if the parents and the GP felt that it was appropriate. Then at page 60 he wrote to Dr Wakefield on 31 July 1997:
You will recall that I have seen this child privately as Dr Mills wasn’t prepared for the child to be seen on the NHS. I have left it with the parents now to inform me whether they wish us to proceed for future investigation. Is this one of the children that you may be able to have funds to cover the child’s admission on the NHS for investigation?”
Do you have any comments on those letters, Professor Booth, particularly the decision to perform a colonoscopy at that stage? First of all, in light of what you have said about previous cases, is it your view that there should have been some sort of screening tests done?
A Yes. As far as we are aware, there may have been some investigations carried out by Dr Mills, but I have not seen those in the records. With the minor symptoms that were outlined in Professor Walker-Smith’s letter, I would not be of the opinion that a colonoscopy should be the first investigation.
Q We have looked at the lengthy process which accompanied the referral of this child and you have commented – I think the word you used was “the extraordinary nature” – of the involvement of solicitors in the momentum for referral. Generally speaking, how do you regard the way in which this child came to be seen at the Royal Free?
A It is certainly very unusual. It is exceptional in my experience for solicitors to play quite a major role in organising the referral of the patient for investigation. We are not clear absolutely as to who sent the mother the information from Dawbarns, but if it was sent by a member of the medical team, that would be I think both exceptional and unacceptable. The story begins with a letter in which there is discussion about this patient’s suitability for inclusion in our study and suitability for investigation in the trial. That seems to be the starting point for a very unusual series of letters between doctors at the Royal Free and the local consultant community paediatrician, who in the correspondence seems, I have to say, very caring with respect to making sure that this patient investigated appropriately and not investigated unnecessarily.
Q It appears that the parents had strong wishes for their child to be investigated at the Royal Free. Does that mean necessarily that it is appropriate to accede to their wishes, for a referral first of all, rather than for the clinical investigation?
A No. It is not inevitable by any means.
Q I have asked you the question before and I apologise, because it is rather an obvious one, but who is the patient in these circumstances whom the clinician should be considering?
A It is the child throughout.
Q As far as the role of the paediatrician is concerned in those circumstances, what is his principal role as far as the patient is concerned?
A The welfare of the patient and the need to make sure that they are appropriately managed.
Q We have seen in a number of the cases we have looked at when we were looking at ‘The Lancet 12’ that there has been considerable parental enthusiasm for the investigations which were carried out on the basis that the parents were desperate for answers. Do your comments about the importance of acting with the child as the patient’s interests as the most important thing, do they apply equally to those cases?
A Yes, they would. I think the desperation of parents to find answers for patients like this is one of the factors which make them so vulnerable to suggestion.
Q It seems, as I say, that as far as the admission was concerned, the ECR was refused and then on 10 November 1997 Professor Walker-Smith wrote to the contracts department of the Royal Free Hospital. That is in the Royal Free records at page 8:
“I am very concerned to have your letter suggesting that [JS] cannot come for an admission on the 12th November. I think it is essential that this child does have a colonoscopy. This kind of service is just not available elsewhere for children with autism and for the special investigations which Dr Wakefield can offer. I have spoken to David Lee and I do hope that it is possible for this admission to go ahead. I am copying this to the parents because of my concern.”
Was it in your view essential that the child had a colonoscopy, Professor Booth?
Q If the suggestion is that colonoscopy as a service is not available elsewhere for children with autism, would you expect it to be?
A One would expect it to be and indeed it was and is.
Q If the children had what symptoms?
A If they had symptoms which clinically warranted that investigation. I think paediatric gastroenterologists would in general use the same criteria for deciding if a child with autism needed investigation as they would in a child that did not have autism, bearing in mind that things like constipation are substantially more frequent in children with autism.
Q Just going on through the admission, he was indeed admitted for those investigations on 12 November 1997 and we have the endoscopy clerking sheet at page 48. We see under “Reason for Procedure”:
“Colonoscopy on Friday
Referred by Dr Mills … ”
Then under “Examination”:
“Bowels – 2-3 times a day normal.
Large amount. Some mucous, sometimes pale”
On examination, we see the abdomen was not distended and there was no tenderness. The reason for the procedure, if you go on to page 50, please, is given as “Autistic”. Going on to the next page, the assessment – no doubt I will be corrected if I am wrong – seems to say:
“Increased vascularity in recto sigmoid area to splenic flexure
? [increased] granularity around caecum ± [increased] vascularity
Lymphonodular hyperplasia of [the terminal ileum].”
There is also a histological description in this case at the bottom of the page:
“Ileum: No active inflammation
Colon: Patchy changes
Caecum: Lymphoid aggregates”
Then on the right-hand side:
“Active cryptitis. Eosinophils + neutrophils”
I should say that procedure was carried out by Dr Thomson. If we can just look in terms of the clinical notes at page 53, which is a ward round with Dr Thompson, we see:
“Endoscopy → terminal ileum – lymph node hyperplasia”
Then there is a reference to starting anti inflammatories. We know that the child was discharged on the same day. I want to ask you, in the light of the symptoms for which he had come in for this procedure, is it your view that the colonoscopy on this child was clinically indicated?
A As I have said, with those symptoms that this patient came in with, a colonoscopy would not have been the first investigation.
Q What is your view as to the apparent role which was taken by the parents in the decision to undertake that colonoscopy, namely, that Professor Walker-Smith was saying, “This is an investigation which could be carried out if the parents wish it to be”?
A He is effectively leaving the decision about the colonoscopy to the parents.
Q Do you think that is appropriate?
A No, I do not think it is, particularly when in the previous correspondence it is clear that they are seeking to find out issues related to possible MMR damage as well. So their view on this is not driven solely by the patient’s symptoms.
Q In fact, after the colonoscopy, there are blood test results available and if we could just look at those so you can tell us what they indicate, if anything. They are at page 19 of the Royal Free Hospital records. If it assists, there are further results reported in the discharge summary, which is at page 17. Can you help us as to the inflammatory markers, as to whether they indicate anything?
A The blood count is normal. It may show that this patient was a bit iron deficient. I cannot see a C reactive protein.
Q I think it is on page 24 and it seems to have been 3.
A That is normal.
Q Then if I can just complete the follow-up on this patient, Professor Booth. There is a discharge summary to Dr Mills, which is the document you just looked at the blood results in at page 17. We see as far as that is concerned the results of the investigations are set out, the colonoscopy, as reported on the colonoscopy form and some manuscript amendments to the histology, which originally said that it revealed no active inflammation but that view has obviously been revised. There is reference to lymphoid nodular hyperplasia of the terminal ileum. That seems to be in accordance with the clinical histology report. And then the child is seen in outpatients by Professor Walker-Smith on 28 January 1998. That is at page 4. I think the first sentence is:
“Normal 2-3 stools a day.”
I find difficulty in reading the next sentence. It then says:
“No blood, no mucous.”
Then at the bottom, is there a prescription for Pentasa?
A That is right, yes.
Q So again, an anti-inflammatory was prescribed. I am sorry – the bit I could not read I think is:
“Has temper tantrums ? related to abdominal pain.”
Then it is:
“Commence on Pentasa …
No constipation treatment at present.”
He writes to the general practitioner at page 94 in the GP records. There is reference at that stage in February 1998 to continuing to have –
“… a good deal of abdominal discomfort and episodes of bloating. He has occasional incontinence at night. He normally passes two to three loose stools a day. He does have episodes of temper tantrums which could be triggered by abdominal pain. Recent investigations did in fact show ileo-lymphoid nodular hyperplasia with a non specific colitis and in particular there was patchy active inflammation with crypt abscesses. I have recommended a trial of therapy with Pentasa … twice a day in view of this finding. He clearly has chronic constipation I feel for the moment that it would perhaps be best to treat him with an anti-inflammatory drug on its own although this may not be adequate to deal with his constipation. If it is not we could consider a dose of paraffin … twice a day after two or three months if there is no significant improvement in his gastrointestinal symptoms. Ideally we would like to see him again in the outpatients ….”
but then refers to the difficulty of seeing the child at all.
“I do believe that the investigations we performed have been worthwhile and have given information that was therapeutically important for this child.”
Can I just ask you this, Professor Booth. If it were suggested that the findings on a colonoscopy provided a retrospective justification for doing the investigation, if it was one where there had been an absence of appropriate clinical indications prior to doing it, do you regard that as giving any kind of justification for doing the procedure?
A No. If there is no indication for doing the investigation before it is done, you do not know what you are going to find when you do it. You cannot use that retrospectively for having done a non-clinically indicated investigation, particularly in this case, where it is not clear that the anti-inflammatory treatment leads to any clinical benefit because the patient has another diagnosis as well, which is severe constipation.
Q Then there are two remaining letters, to complete matters, Dr Mills to Professor Walker-Smith at page 93:
“[JS’s] mother contacted me soon after her appointment with you to ask my advice.
She was of the view that the Pentasa had resulted in increased frequency of bowel motions and increased discomfort. I suggested that she withheld the medication of several days and the restarted it to see if the symptoms recurred.
I have advised her to contact you, although she indicated that she had not been able to do this previously.”
He then asks for details of a referral, whether Professor Walker-Smith thought it was appropriate for [JS] to be referred to a paediatric gastroenterologist nearer home.
I think it is correct that there is not a reply, at least in the records, to that letter from Professor Walker-Smith, is that correct?
A I have not been able to find one.
Q Lastly, there is a letter from Dr Mills to the GP, copied to Professor Walker-Smith, and that is at page 89, referring to particular difficulties because of the child’s behaviour. At page 90 he is expressing some doubts that:
“… [JS]’s difficult behaviour is in any way related to feelings of discomfort or pain … I do not believe that pursuing treatment of his inflamed bowel will make any difference to managing his behaviour.”
In fact, as far as we can tell from the records there was not any gastroenterological follow up.
Just two matters which I may not have asked wholly clearly: with the normal blood tests (as we know they were) is it your view that a colonoscopy was in fact clinically indicated?
A In this patient?
Q Overall, is your impression that this was a clinical or a research admission?
A Given the background correspondence, where there was reference to this patient being included in a study and investigated as part of a trial, this was a research investigation.
Q Do you have any hesitation in coming to that conclusion on this case?
A No, I do not think so, not having seen the correspondence that led up to the admission.
MS SMITH: Sir, that concludes all the questions I have to ask about Child JS. I see it is 4.30 and I rather anticipate that you would not want to embark on any other matters tonight.
THE CHAIRMAN: Yes, I think that is absolutely right.
MS SMITH: Sir, I ought to have mentioned one matter which I am told had not filtered through to you and if it had not I apologise. I will conclude my questions in chief of Professor Booth tomorrow. He is not able to attend on Monday because of a long-standing, impossible to cancel, professional engagement, which indeed he told us about when he was first given the dates for this hearing, and so I am anticipating resuming his evidence on Tuesday. I should tell you that he has very kindly made sure that he is available for the rest of the week, with some difficulty so far as Friday is concerned. I do not anticipate, from the amount of information I have been given by my learned friends as to how long they are going to be in cross-examination, that a problem will arise.
You will be aware that we have one very short expert who I also have to deal with next Friday, but that is so you are up-to-date with where we are. Obviously I will tell you if that changes in any way but, as I say, we will not be able to have Professor Booth and therefore will not be able to sit on Monday.
THE CHAIRMAN: Was Monday as a non-sitting day known to the GMC because we certainly were not informed of this?
MS SMITH: I am sorry, I think that might have been an omission by me I have to say. Would you give me a moment? (Pause) Sir, when you say “known to the GMC” I am not sure if you mean us or …
THE CHAIRMAN: No, because we had a list of non-sitting days provided to us, which was in consultation with the Panel members along with the lawyers and the availability of the witnesses. I am looking to see if any of the Panel knew this Monday was a non-sitting day because I did not have it in my diary.
MS SMITH: It is pointed out to me that when the original non-sitting days were given to you it certainly would not have been known at that stage because although Professor Booth knew about his commitments, the timings have been pushed back for all kinds of reasons so that when the first non-sitting days were fixed, no, the answer is we would not have known about this Monday and you would not have been told about it. As I say, as far as I am aware it is long-standing as far as Professor Booth is concerned, but we were notified and if it did not filter through to you I should take responsibility for that.
THE CHAIRMAN: I am asking anybody to take responsibility, I am just making a request if any date is known to be a non-sitting day then I think the information should be passed on as quickly as possible. The difficulty with being informed at the last minute there is very little we can do to organise something else. If we had known about this maybe a week or two weeks before maybe something could have been organised.
MS SMITH: I appreciate that and I can only say I am sorry.
THE CHAIRMAN: Is it definitely confirmed that Monday is a non-sitting day because Professor Booth is not available?
MS SMITH: Yes, but may I say Professor Booth has gone to the most inordinate lengths to clear himself of his outpatient appointments on Thursday and Friday so no difficulty arises as a result of any delay that might be caused. I am saying that slightly tentatively because it is unpredictable for me how long cross-examination will take, as it is for everybody, so we will have to revisit that issue. As I say, I do have another short expert, but I do not envisage problems arising.
THE CHAIRMAN: Are you going to be most of the day tomorrow completing your examination in chief? I am not going to hold you to it but it would be helpful to have an idea.
MS SMITH: Mr Thomas tells me I will not be all day!
THE CHAIRMAN: On that optimistic note we will finish.
MS SMITH: I think I will be more than the morning, sir, and I would hope not to be a whole afternoon but I really do think we have to see how it goes.
THE CHAIRMAN: Absolutely, I fully understand. Mr Miller, you wanted to say something?
MR MILLER: Having heard your last remarks, we have been discussing for the last two days, since we knew there was a problem about Monday, the timetable. If we are not going to be sitting on Monday I am not terribly happy about embarking on cross-examination if I am the first cross-examiner, at 3.30 on a Friday afternoon and then breaking off until Tuesday. I anticipate that I will comfortably finish dealing with this witness in two days, and I do not know whether there is anything else following me or before me but I echo Ms Smith’s views about the timetable, we are going to finish the evidence by the end of the week.
THE CHAIRMAN: Thank you. Mr Coonan, is it possible for you to give your position? If not we appreciate that.
MR COONAN: Yes, subject to this: as you know I have a slight housekeeping problem that I need to get the transcript of tomorrow served by email to America. There has been no problem at all with the transcript up till now, I have sufficient instructions, but tomorrow would be a problem, and so in effect Mr Miller is quite right, we have discussed this and not knowing precisely how long Ms Smith will be we thought, subject to your views, of course, that cross-examination would begin – once we knew about Monday – on Tuesday morning.
THE CHAIRMAN: Mr Hopkins?
MR HOPKINS: I echo what you have already heard.
THE CHAIRMAN: I think it would not be appropriate to start cross-examination tomorrow, particularly now that … It would not have been the ideal situation anyway, even if Monday was not a non-sitting day but now that Monday is a non-sitting day I think it might be quite awkward to start and then break off in the middle of cross-examination.
Can I suggest, we have noted everybody’s views and they make a lot of sense, let us put it that way, but we will make a final decision on it tomorrow depending upon what time Ms Smith’s finishes.
If that is all we can do today we will adjourn and resume at 9.30 tomorrow morning.
(The Panel adjourned until 9.30 on Friday 12 October 2007)