GENERAL MEDICAL COUNCIL
FITNESS TO PRACTISE PANEL (MISCONDUCT)
Wednesday 22 August 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
DAVID HOWARD CASSON, continued
Re-examined by MS SMITH 1
Questioned by THE PANEL 4
Further Re-examination by MS SMITH 17
Further cross-examination by MR MILLER 20
DAVID MAXWELL SALISBURY, Affirmed
Examined by MS SMITH 21
THE CHAIRMAN: Good morning everyone. Good morning Dr Casson. Ms Smith, you were about to re-examine Dr Casson.
DR CASSON, continued
Re examined by MS SMITH
MS SMITH: I have a few questions arising out of what you were asked by defence counsel yesterday. Firstly on some of the factual background: when you were answering Mr Miller’s, on behalf of Professor Walker-Smith, questions yesterday he asked you about the letters that you wrote to the parents following up the appointment for the patient to be admitted, do you recall?
A The letters informing them that they were to be admitted, yes.
Q You said, “Of course, they get a letter from the Admissions Department”.
A I assume they would get a letter from the Admissions Department as well.
Q What was it that dictated whether you would write as well?
A I am not entirely sure what that would be. There must have been some extenuating circumstance, whether it was at the request of one of the consultants or whether the parents required confirmation, they may be possible reasons.
Q Was it part of your normal duties on more than the occasions that we have got examples of here?
A I would have done it on occasions but it would not have been a regular occurrence.
Q The other question generally I wanted to ask you is with regard to the questions Mr Miller asked you about the outpatient appointment system: just so we are absolutely clear, I think you said you would have your own patients that you would be seeing in outpatients, is that correct?
A They would not be my patients. Patients would be seen in the sequence generally in which they arrived at the clinic and we would pick the next set of notes off the top of the pile, as it were, and the clinic would be staffed by myself and by one of the consultants, and then I would see the patient – the patients would be seen in the order in which they had arrived, generally, and then I would discuss with them if necessary.
Q If you were the one who was seeing the patient in outpatients would you do the notes?
A I would make the written record in the notes and dictate the letter.
Q Would that patient who you have seen and you have written the notes for in outpatients, would that patient necessarily also see the senior doctor, the consultant?
A Not necessarily. That would have happened on occasion.
Q Physically, where were you vis-à-vis the senior doctor who was also seeing patients?
A I would have been in a consulting room nearby.
Q As far as the consultants themselves are concerned, you were asked some questions by Mr Hopkins on behalf of Professor Murch about the other consultants in the department, and I wondered if you could help us, during the time you were there were they all there all the time? Professor Walker-Smith and Professor Murch you have told us were, was Dr Thomson also there when you arrived?
A From my recollection, I think he arrived a little bit after I had arrived, by a month or so.
Q What was your understanding of their respective seniority?
A In terms of being responsible for patients, we would all have had an equal responsibility. In terms of seniority, vis-à-vis how long the experience they had, Professor Walker-Smith was obviously the more senior consultant, and then Dr Murch and then Dr Thomson.
Q Another general question that Mr Hopkins asked you, he asked you about the inclusion of lumbar punctures in the Ethics Committee protocol, and you said, “I recall it was a potential issue with the ethical application.” Can you help us as to what you meant by that?
A I think a lumbar puncture is an emotive investigation in many circumstances, and it would have obviously been a point that an ethics committee would have deliberated over.
Q And that was something that was discussed was it, that you recall?
Q Just a couple of questions on the individual patients: if you would go to the Royal Free Hospital records for Child 2, please, and turn to a page you have been asked about by both counsel, page 152. That is the Great Ormond Street fax sheet and it had a note written on it. Do you recognise the handwriting on that note?
A I am not sure whose handwriting it is.
Q If we look at the letter behind it, pages 153 and 154, this was the letter accompanying it from Dr Surtees to Dr Cass. I would like to look at the content of it:
“Thank you for letting me see this eight year old boy … What is unusual is that there have been three episodes of regression … Following each … he has never regained the skills lost. On formal neurological examination there are no focal findings. I am afraid that I do not recognise this as a defined neurometabolic or immunological disorder. However, I do think reinvestigation is necessary if only to make an authoritative decision on what he does not have. To this end I would suggest the following …
1. Magnetic resonance imaging …
2. A repeat EEG …
3. Repeated metabolic investigations …” – which he sets out.
4. Detailed immunological investigations looking at both T and B cell function …
5. A detailed dietary review, and
6. A gastro intestinal consultation.”
Can you help us, doctor, and tell me if you cannot, as to whether of those investigations that he is suggesting would have required lumbar puncture?
A The investigations listed specifically do not refer to any investigations requiring cerebrospinal fluid. However, repeated metabolic investigations “which should include”, which is suggesting they should include these.
Q But none of the ones that he is suggesting require testing on cerebrospinal fluid, is that correct? So none of the tests that he is requiring lumbar puncture?
A None of the tests from this … Sorry, may I just read the introductory paragraph again?
Q Yes, please do. I think paragraphs three and four are probably the ones you will need to look at.
A (Pause) No, they would not require lumbar puncture.
Q If you go back to the fax at page 152, keep your finger in it, and turn back to page 18, in the middle of the page it says it was envisaged that the CSF would be tested for, and we see measles, cytokines, is that right?
Q RT-PCR and lactate pyruvate glucose.
Q If we look back at page 152, there is no reference to the RT-PCR: can you assist us as to what that means?
A Reverse transcription (sic) polymerase chain reaction. Excuse me if I do not get the details right but I think it is a way of amplifying RNA in order to – the genetic information that would be there from small amounts of sample in order to generate larger amounts of sample which are available for analysis.
Q Can you tell us, as far as you were aware, why was that test being carried out on the CSF of these children?
A I cannot be specific about that, whether it was to – it may have been there to look for evidence of measles.
Q To save me having to go to other children’s records was that a test that was done on other children who had cerebrospinal fluid for testing?
A I think it was, yes.
Q Would you put away the documents for Child 2 and get out the GP records and the Royal Free Hospital records for Child 8. Mr Miller asked you about the discharge summary, which is in the Royal Free Hospital records, for Child 8, which is on page 15. The end of the letter, which you will see says, at page 16:
“These results therefore are not indicative of marked ongoing inflammation. The results from Dr Wakefield’s investigations … would be available from him.”
There was no treatment suggested in that letter and Mr Miller asked you whose decision that would have been and you said it must have been the decision that was made after discussion. That was in November 1997, but if we go on to the GP records at page 74, this is a letter dated January 1998 from Dr Wakefield to the GP simply saying that he has been contacted by mum:
“… and realise that we have not spoken for some time. We are now coming up to the 38th child … and the findings have been remarkably consistent. Please find enclosed the first paper covering the initial 12 children, including [Child 8] …
We have had some success (striking, in some cases) in treating these children with Mesalazine. Both gastrointestinal and behavioural improvements have been noted. I have written to Professor John Walker-Smith suggesting we start [child 8] on Mesalazine, and he will be writing to you in the near future.”
If we can then follow it through into the Royal Free records at page 14 we do indeed see that followed through by Dr Wakefield to Professor Walker-Smith:
“[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, although 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 will keep in touch with [Mrs 8] and Dr Jelley, the general practitioner, to monitor progress in view of the long distances involved.”
Who would Jill be?
A I presume that is Jill Thomas, who is the research nurse.
Q Then if we look at page 13 we see a letter from Professor Walker-Smith to Dr Jelley:
“I understand that [Child 8] continues to have gastrointestinal symptoms. I do believe that it would be appropriate to give [Child 8] a therapeutic trial of the 5-ASA derivative of Pentasa …”
Is that one of the anti-inflammatories in the salazopyrin group?
A Yes, it is.
MS SMITH: Thank you very much doctor. I have no further questions but the Panel may
THE CHAIRMAN: Dr Casson, as I said earlier, and it seems like a long time ago, maybe a couple of days ago, I did say that before the end of the evidence the Panel may have some questions, and if they do have some questions then I will introduce them to you. First of all, Dr Webster is a medical member. That is the gentleman on my left.
Questioned by THE PANEL
DR WEBSTER: Good morning. Mr Hopkins asked some of the questions, general questions, to try get the sort of background of the situation, and from Mr Hopkins’ questions you told us that there were two lists for endoscopies and they were done away from the ward in the endoscopy suite.
A One of them, the sedation, is done in the endoscopy suite. The list that was introduced at a later date was a general anaesthetic list performed in theatres.
Q Right, but away from the ward?
A Away from the ward, yes.
Q You said that four patients a week were dealt with. It is not clear to me whether that is four autistic patients or four patients in total for endoscopy?
A That is four patients in the general working of the unit, not specifically children with neurological problems, but children who might be investigated for other bowel conditions, generally inflammatory bowel diseases.
Q So that would be four a week, but you could do sort of eight or more with the two lists?
A Four on the list which involved the children receiving sedation, and a similar number, yes, would be possible on the general anaesthetic list.
Q What proportion of those patients were the autistic children in those projects?
A A small proportion.
Q Could you give us a figure?
A I really could not.
Q Would it be one a week or one a fortnight, or---
A Possibly even less than that, to my recollection.
Q Now, how big was Malcolm Ward, how many beds?
A I think about twelve beds, something like that.
Q Were these in single rooms, or was it a sort of Nightingale style ward?
A They were in individual areas, so there would have been several beds together.
Q What, sort of four-bedded bays, or something like that?
A Yes, four to six-bedded bays, yes.
Q The ward was specifically for the Department of Paediatric---
A Sorry, I think there were also rooms as well, a few rooms.
Q Right, but was the ward specifically for the Department of Paediatric Gastroenterology?
Q Did they have beds anywhere else?
A Did the gastroenterology unit have beds anywhere else?
A No. There was a general paediatric ward as well, which if there had been an overflow it would have been possible to use beds there.
Q How common would autistic children be as patients in a sort of general paediatric setting?
A Not common.
Q So how familiar would the nursing staff be with the management of these people? Presumably, they would be quite challenging at times?
A I think they are used, generally speaking, to challenging behaviour, but specifically this patient group, it is difficult for me to know because each nurse would have had their own individual experience in their training and previous career.
Q How did the autistic patients cope with the programmes that they were based in?
A I think it was very variable really. Some appeared to cope well and others found the experience difficult.
Q Which end was the majority?
A On the whole I think they dealt fairly well with the experience.
Q What about the bowel prep for the endoscopy, what form did that take?
A You will have to excuse me, because I have been using so many different protocols for bowel prep and I do not remember what the specific bowel preparation was. I would have to---
Q I do not want to, you know---
A It would generally have been an orally administered medication, which was a laxative medication, and that can be either single doses or continuous over a longer term infusion, as it were.
Q Right, but taken by mouth?
A Taken by mouth.
Q Because I think when you were talking about Child 1, you mentioned the nasogastric tube for the bowel prep.
A Yes. This is what I mean by continuously administered infusion of the medication.
Q Right. So a nasogastric tube to me is not quite the same as by mouth. So how frequently were nasogastric tubes used?
A I am afraid I cannot recall how frequently they were used.
(Fire alarm sounded)
Q It is all right, it is a test, I think I am right.
THE CHAIRMAN: I believe it is just a test, but I think if we can just hold on to the proceedings just for a minute.
A It is not a lie detector test then? (Laughter)
THE CHAIRMAN: No. Thank you.
DR WEBSTER: So sometimes nasogastric tubes were used then for the bowel preparation?
Q Was that done under sedation?
A Generally not.
Q How did the patients cope with that?
A On the whole, because of the expertise of the nursing staff, fairly well.
Q You were there in a training post as a junior doctor. Did you have any qualms or apprehensions about the programme that these patients were going through at the time?
A I think that there were children whose parents reported significant bowel conditions or bowel problems, and therefore they merited investigation from that perspective, yes.
Q That is how the parents felt. How did you feel?
A I felt that if there was something that could be done to help these children, then it should be pursued.
Q The attitude of the nurses?
A I am terribly sorry, could you be a little bit more specific? What do you mean specifically?
Q Well, the attitude of the nurses to these patients going through on this programme.
A I think that generally we were all of a similar mind, that if there was something we could find that would be helpful, then it should be pursued.
Q You mention how you frequently saw the clinicians, presumably on the ward, in the clinics, and so on. How frequently did you see or meet Dr Wakefield?
A Fairly frequently. As I say, it was a very open department and there were several meetings at which he would have been present, and he was also in the hospital, so I would have encountered him on many occasions.
Q So the meetings you are talking about, this is what, the histology meeting and the---
A The histology meeting.
Q ---radiology meeting?
A I do not recall him being at radiology meetings. Certainly the histology meeting and the general business meeting of the firm, yes.
DR WEBSTER: I think that is all my questions. Thank you.
THE CHAIRMAN: Dr Moodley, sitting on my extreme right, is also a medical member.
DR MOODLEY: I want to ask a general question. You were appointed as lecturer to Professor Walker-Smith, an honorary senior registrar.
Q So was your job mainly research, or teaching, or clinical?
A The job was mainly clinical.
Q Was there a research element built into it?
A There was the idea that I would pursue some research, yes.
Q Fundamentally it was the same as a clinical senior registrar post?
Q Who was your supervisor?
A In terms of?
Q Your educational supervisor, clinical supervisor.
A I do not recall one specific person being named as my educational supervisor, although as head of the department it would have been Professor Walker-Smith, but everybody was involved in my training, as it were.
Q You told us about how the patients got admitted via outpatient clinic appointment first usually, and then they were admitted, but you have also said it was a busy department. Who managed the admission list? How was that managed? Who decided when a patient came in?
A Again, I think it would have been a consultation between the medical personnel on the team and those people in charge of the ward, to check that there would be sufficient availability, and that there would be sufficient availability on the endoscopy lists that they were intended for.
Q So was that discussed at weekly meetings?
A I do not think there was a specific forum. It would have been a business telephone call to the ward or to the secretaries who kept the endoscopy lists.
Q You have clerked in many of these patients that came in. Did you clerk all the patients, or some specific patients, particular patients?
A I would have clerked those who were there when I was there, as it were. So, for example, if I had been away on holiday, or something, then I would not have clerked those patients, but generally it was whoever was available.
Q On the ward were there a number of different research projects going on?
Q Is that why there was a protocol book?
A No. The protocol book was really a clinical document which indicated if a certain test was requested what that test required, so it was generally outwith research; for example, if biopsy samples were needed to be sent for a specific analysis, what needed to be done and where they needed to be sent, or if a particular biochemical test was required, when the test needed to be taken, how it needed to be taken and where it needed to be sent for analysis.
Q Was there another set of protocols related to the different research projects?
A There was not, no.
Q Was there something referred to as the Wakefield protocol?
A I do not recall specifically something being referred to as the Wakefield protocol.
Q Can we look at Child 8’s notes, please, page 94.
THE CHAIRMAN: Royal Free?
DR MOODLEY: Royal Free, yes – sorry, 93. Under “Plan” it says “Dr Wakefield protocol”. Can you tell us what this document refers to, this endoscopic clerking sheet?
A This is a record of an endoscopy with cartoons of the bowel that would have been visualised at endoscopy. The one on the right with markings on it is the colon, and the one on the left is the oesophagus, stomach and first part of the small bowel. Presumably it is a record of what was visualised at endoscopy, and the crosses would indicate where biopsies were taken from. Then there are areas for recording this, the initial assessment following the endoscopy, the plan and then the histology findings.
Q Who would this be filled by, do you know?
A Presumably by the doctor doing the endoscopy.
Q You do not know what Dr Wakefield protocol is referring to there?
A I presume it is euphemistic for the general scheme of investigation.
Q A number of the patients in your discharge summaries recorded to have raised lead levels. When you got the reports back, the blood tests back, if they were abnormal findings what would be your usual routine? What would you do?
A I think they would have been discussed within the department as to whether anything further needed to be done.
Q Do you recall discussion about abnormal lead levels in any of these patients?
A I do not recall the discussion but obviously in terms of the letter that I wrote about the one child with the very significantly elevated lead level there would have been a discussion regarding that which resulted in the letters I sent.
Q That letter that you wrote is just the recording of the fact that the lead level was raised but does not actually say that anything needs to be done about it.
A I think one of the letters records some consultation with a doctor from the poisons unit and subsequently that collation might have been required in a child with a slightly further elevated lead level, but at that time no intervention was required. It further said that we should seek a possible cause for lead ingestion, that being most likely to be pica.
Q It is Child 9, page 66 ---
MR MILLER: I did not go through this with this witness because he was not involved in the investigations but in general terms I said to him there was further investigation about this. There is a lot of correspondence that follows in the notes where the lead levels were investigated between Dr Spratt, the paediatrician in XXX, and the Royal Free and Great Ormond Street and they identified the source of it in the child’s house, but because he was not involved I did not ask him about it. It does go on in the bundle with other doctors taking up the cudgels on behalf of the child and it is resolved. They find some problem with the wallpaper or lead paint in the whole house.
THE CHAIRMAN: Thank you for that clarification.
DR MOODLEY: Child 12 in the Royal Free notes, page 29, in the second paragraph you say that abdominal x-ray showed marked faecal loading but on discussion with Professor Walker-Smith you decided that the patient should go on olsalazine. In the notes of your outpatient assessment you say that the mother had tried liquid paraffin but had not persisted. Could you say what you thought was the rationale for using olsalazine instead of being more aggressive with treating the constipation?
A I think the rationale would have been that initial attempts to treat the constipation had been unsuccessful; that bowel symptoms were possibly related to the syndrome that was being described and that the syndrome being described had anecdotally been improved by use of these agents and therefore it would seem a reasonable therapeutic alternative to try that direction rather than treating the constipation per se, which possibly may have been a result of the ongoing bowel problem and, furthermore, to try two treatments at the same time would lead to confusion as to what treatment was actually being helpful.
Q Was it the failure of the mother to give the child the medication?
A I do not know exactly why that failed.
DR MOODLEY: Thank you. I have no further questions.
THE CHAIRMAN: Mrs Dean is a lay member.
MRS DEAN: I also wanted to ask some general questions and I wanted to start by going back to something you talked to my colleague, Dr Webster, about. You explained that generally the unit carried out about four colonoscopies a week.
A With the sedation list, yes.
Q Possibly eight overall if you were using the general anaesthetic list as well?
A It has to be understood that the general anaesthetic list was also used for investigation which would have required just an upper endoscopy so many of the slots would have been taken over for that. The space would have been available to do possibly eight colonoscopies. The space may have been taken up by other investigations.
Q I take it, generally speaking, that was a relatively rare investigation amongst the children who were admitted to the hospital?
A No, it is not a rare investigation. It is a central point in diagnosis of most serious gastroenterological conditions and so it is a fairly common investigation in those terms.
Q Would it be right to say that most of the children – and I am talking about children generally, not just the ones in this particular set – who were admitted to the Royal Free Gastroenterological Department at that time underwent colonoscopy?
A I cannot give you the figures to tell you it was the majority of the patients admitted. It was certainly a very significant proportion.
Q It might help me if you could explain what other tests you would routinely carry out on children who come in for general investigation.
A Many of them would have been for observation or for observation of feeding problems or diarrhoeal type problems for association of those with other blood tests and stool analysis.
Q Just for observation?
A Often so, yes. Obviously some of the patients would potentially require surgical intervention as well and then they would have been admitted to the ward as well.
Q All these children would have been seen generally in the outpatient clinic first before they came in.
Q What kind of presenting symptoms in the outpatient clinic would lead to a decision to admit specifically for an endoscopy?
A The main indication is to look for inflammatory bowel disease for colonoscopy and the symptoms thee would have involved bowel symptoms such as bloody diarrhoea or not and possibly abdominal pain, but most significantly more general features such as poor appetite, weight loss, low energy levels, low mood in association with possibly suggestive blood tests.
Q I wanted to ask about the blood test. You will recall that I am a lay member. My understanding is that you can carry out a blood test which will show what has been described to us here as an inflammatory marker. My understanding of that is that it is something that indicates that there is some kind of inflammation in the body, is that right?
A That is correct.
Q Would you always carry out those tests before you carried out the endoscopy?
A Generally speaking, yes. However, there would be occasions when the history itself was convincing enough and when blood tests would have been done but maybe not at the point of outpatients but when other investigations were being done just so that everything could be done together which generally would make it easier for the child.
Q If you had a blood test that showed no such marker, why would you then want to go on to carry out a colonoscopy?
A It needs to be understood that inflammatory markers, although they are very useful, do not give the whole picture and there must be a more holistic approach. In an holistic approach there will be patients in whom inflammatory markers are not particularly helpful and yet who, at endoscopy, will have significant features.
Q Can I also ask you to tell me what Toddler’s diarrhoea is?
A Toddler’s diarrhoea is so-called because it has its onset generally around the time the child starts to toddle. The characteristics of the diarrhoea are generally that it contains undigested food probably indicating a rapid transit through the bowel. However, on the whole there are no other what we might call systemic features such as a weight loss or general illness associated with it. It follows generally a self-resolving course.
Q Is it a relatively common thing?
A It is relatively common and benign.
Q Presumably it is not something that would indicate the need for a colonoscopy.
A Not per se if that was felt to be the correct diagnosis.
Q I wanted to ask you about these lumbar punctures. Would lumbar puncture be carried out on the ward in relation to the children who were generally admitted?
Q That was something that was specifically just part of the programme of investigation for this group of children.
Q The final thing I wanted to ask you about was the clinical histopathology meetings. Did they take place every week?
A Generally, yes.
Q How long generally was it before a biopsy was reviewed at this meeting?
A Generally the biopsy would have been taken at the endoscopy which I recall was on a Monday. Biopsies are then sent down to the pathology department where the slides are prepared. The slide would then have been reviewed in the intervening period by one of the histopathologists who may well have written a report by that stage and then would have been demonstrated to us on a television screen at the Friday meeting where the general discussion would have taken place.
Q Can you ever recall situations where perhaps two or three slides, or one slide, were reviewed again some weeks or even months later?
A I am afraid I cannot recall specific instances but it was certainly a forum where, if previous material wanted to be reviewed, then that could be done at request.
MRS DEAN: Thank you very much.
THE CHAIRMAN: Ms Golding is a lay member.
MS GOLDING: I have some general questions first. Prior to your post at the Royal Free were you involved in any research projects at all?
A No, only inasmuch as I was a doctor who was there at the time when maybe a global research project was going on; for example, when I was doing my neonatology there was a general multi-centre study going on about the use of sufactin in order to improve those children’s care so I would be involved, as any junior doctor would at that time, in randomising patients and then administering treatment as necessary. My involvement was no more than that.
Q Was your name on the report that came out afterwards?
Q Did you read up the aims of this particular study before getting involved?
A The aims of the study were part of the discussion within the department so in terms of reading up I was aware of some of the literature. My main knowledge came from discussion within the department.
Q Were you clear about what each part of the investigation being carried out were for or why they were being done?
A I was clear that the gastroenterological investigations were to exclude gastroenterological diseases; that supplementary investigations were to exclude any other neurological disorder, I was clear about that, yes.
Q Were you aware of any ethical issues regarding the use of children in research?
A I am always aware of the particular place of children in any medical procedure or practice, whether that be research or day to day clinical practice.
Q Was that something that was discussed as part of the general discussion in the department?
A The department dealt only with children and had a good research record and therefore those sorts of issues were constantly at the fore of discussion within the department, yes.
Q For all the children being admitted to the Malcolm Ward, were they all inpatients for a week at a time?
A As far as I recall, all children coming in for investigation of inflammatory bowel diseases would, as far as I recall, be fitted into that week programme which allowed all investigations to be done in close proximity and the results to be available at the end of the week and therefore a definitive diagnosis made and treatment commenced within that one week period. That was for children with suspected inflammatory bowel diseases. Other children would have been out with that week’s schedule.
Q The children who were not part of this study would not have had as many tests as these children.
A The tests the children coming in for investigation of inflammatory bowel disease would have included the endoscopic procedures, generally a colonoscopy and also a barium meal and follow through. That would have allowed examination of the whole of the gastrointestinal tract. They would also have had blood tests basically revolving around inflammatory markers. Other tests would not have been required.
Q Would the children who were part of the study have been having the same tests as the other children plus these other tests back to back?
A I do not understand what you mean by back to back?
Q One after the other rather than a day in between.
A I would have to refer to the proposed schedule. My recollection is that they had an endoscopy on the Monday. I would have to make reference to the schedule, I am afraid.
Q Were you present for the lumbar punctures at all?
A I think I am on record as having performed one of the lumbar punctures. The other ones I cannot recall whether I was there or what the exact circumstances were.
Q To your knowledge was the measles virus found in any of these spinal fluids?
A I really cannot be sure of the details of that.
Q Who would the results of that go to first?
A I think that the results were being looked at by Dr Wakefield’s research team, from my recollection, and therefore they would have been available to his team initially.
Q Who was in his team?
A That would have involved several research scientists working with him.
Q You were asked this question a couple of times but I do not think that you actually answered it either “yes” or “no”. You were asked whether you had any direct communication with Dr Wakefield in relation to the fact of or the nature of the investigations that were being carried out and you replied that the department was a very open place for discussion, so general discussion was taking place. You were also asked a similar question and you gave a similar answer. I wonder whether you can answer “yes” or “no” as to whether you had direct communication. Did you speak to Dr Wakefield about this study on a one-to-one basis or question him about it?
Q What did you question him about?
A When I say on a one-to-one basis, there would have been free discussion between me and him with people around.
Q I do not mean in a little corner somewhere but did you talk to him directly about this study?
A I must have done on occasion, yes.
Q Did you have any concerns about the study? Did you ask him about any concerns or any issues that you felt you needed to make?
A I cannot recall having done so, no.
Q What is indeterminate colitis with lymphoid nodular hyperplasia?
A Indeterminate colitis is a condition where there is inflammation seen within the bowel and yet there are not sufficient diagnostic features to confirm a diagnosis for one of them in that inflammatory bowel disease is generally accepted as being Crohn’s disease or ulcerative colitis. That is to say that the findings, that is generally the histological findings, the biopsy material as seen under the microscope, shows some inflammatory changes. However, they are not of a sufficient nature to make a diagnosis either of Crohn’s disease or ulcerative colitis. So, it is merely describing an inflammatory condition in the bowel for which there is insufficient information to give, as it were, a definite diagnostic category to. Lymphoid nodular hyperplasia is generally a macroscopic, that is the picture that you see when you are doing the endoscopy, appearance of enlarged lymph nodes, lymphonodulars, and the lymph nodes are hyperplastic, i.e. they are larger than you might expect them to be, and is an association presumably between the observation of lymphoid nodular hyperplasia, the large lymph nodes, and sufficient histological detail to make a diagnosis that there is some inflammation going on but insufficient to be specific as to the diagnostic category.
Q When you had the histology meetings, would the endoscopy reports be available at the same time?
A The format of the endoscopy meeting was that the team would be present, the histologists would be sitting at a desk with a microscope and the images she saw would be projected on to a screen that we could all see. It was my job to have the notes and to give a brief history of the condition and generally the endoscopic findings, the macroscopic findings, as a prelude to the report of the histopathologist.
Q How would you know which child would be going on to the study?
A Presumably that was from direct information from one of the consultants.
Q Would that be verbal?
Q Would that be after the outpatients?
Q Why did you write in a few of your letters that Dr Wakefield would be deciding on further investigations because you were asked whether Dr Wakefield played any part in decision making as to the investigations and you said that you could not recall whether for specific patients he would have made a decision about what investigations would be undertaken and yet you write in your letters that he would be making a decision, so why would that be?
A I think it was probably because, in terms of collating a lot of the information and having all the results available, they would be done presumably by Dr Wakefield and therefore any exclusions from that would be apparent to him.
Q How does the olsalazine help? What exactly is it?
A Olsalazine is one of a group of compounds that come under the general heading of five ASAs which are five aminosalicylic acids. These are preparations which are very similar to an Aspirin-like drug and therefore have an anti-inflammatory effect where they touch the bowel, as it were, and therefore they are used as bowel anti-inflammatory medication.
Q Are they stopping pain?
A They are there to try and suppress the inflammation which is a feature of inflammatory bowel conditions.
Q This seems to have been used for those children in the study. How was that supposed to help them? What was it trying to do?
A The main indication was that it was to suppress bowel inflammation and therefore to try and address the symptoms which are consequent upon bowel inflammation which would generally be diarrhoea and possibly abdominal pain, those sorts of features.
Q Overall, would you be able to say whether the children you saw benefited directly from the tests that they were given and any subsequent treatment in terms of the olsalazine and some of the other prescriptions?
A That is quite a difficult question because the important yardstick for that in many situations is the parental report of whether the medication had been beneficial and changes consequent upon starting the medication. So, where possible, I sought to record the parental impression of what had happened.
Q Most of them went through quite a number of invasive tests and, at the end, it seemed to me that there is a diagnosis of constipation and they are given something which might help that over a period of time. How difficult is it to diagnose constipation in children such as the ones in the study? How difficult would it have been to diagnose that?
A Sometimes it is very obvious from the history and the examination that constipation is the problem. At other times, it may not be so obvious, the reason being that sometimes it is very difficult to know exactly the bowel habit of children, especially those with neurological problems. Furthermore, constipation may manifest as apparent diarrhoea in terms of what we might term as overflow diarrhoea.
Q Would you explain what that is.
A If children retain faeces to some degree, maybe some liquefaction of those faeces and then the leaking of faeces which may be interpreted as diarrhoea.
Q In the letters to the parents or to the GPs where it talks about medications prescribed for therapeutic purposes, what would that mean?
A Therapeutic purposes would mean in order to try and ameliorate any of the symptoms reported by the parent or the child.
MS GOLDING: Thank you very much.
THE CHAIRMAN: Dr Casson, one of the advantages of coming at the end is that a number of the questions that we might have asked you have already been asked, but there are maybe two or three further clarifications that I need to seek from you. I think that this department of gastroenterology at the Royal Free, if I have understood it right, was a very proactive unit in investigating children with gastroenterological problems.
Q I think you said that a significant number of them had colonoscopies and maybe even upper GI endoscopies.
Q Did you have many admissions of autistic children, apart from the study, with gastroenterological problems on to the unit?
A Sorry, are you referring to patients who were not included in the 12 patient ---
Q Children who were not included in this study?
A There were other patients, yes.
Q If I understood correctly, you said to my colleague, in answer to a question about lumbar puncture, that that was not an investigation which was normally performed, but what about the children with autism who also had gastroenterological problems? Would you say that lumbar puncture was one of the investigations that would, should or could be performed?
A The lumbar puncture would not specifically yield any information about bowel inflammation, so in that regard it is not a diagnostic test for any ongoing bowel inflammation.
Q But additionally, if they were also autistic?
A I think the importance of the lumbar puncture was to exclude other conditions, conditions which might be disposed to a diagnosis of autism, particularly the mitochondrial disorders that have been referred to.
Q I know it feels longer but it was a couple of days ago that you were asked this question, and I think you have been asked since then as well, you were asked about the investigations in the protocol, and if I understood correctly from your answers, these were investigations that were in the protocol and they were performed on these children?
Q Did you have the authority to say that because your findings on this particular child were so and so, therefore one or the other investigation, although it was in the protocol, need not be done?
A I think that, as I said, that is a very open unit and certainly that sort of concern would have been listened to sympathetically.
Q Similarly, looking at the other end of the scale, if you examined a child and found that more investigations were needed than were in the protocol, did you have the authority to order those investigations?
A I think once again the same answer applies, that would have been amenable to very open and ---
Q Yes, because some of the children had more investigations performed.
A I am not sure what you are referring to.
Q For example, chest x-rays, ECGs, they were not part of the protocols.
A No, they would have been dictated by clinical need above and beyond what had initially been apparent.
Q Exactly, that was the point I was asking about. Lastly, would you look at the Royal Free Hospital records for Child 2, and that is page 153. This is about a question you were asked by Ms Smith this morning. This is the letter that was faxed to you, and we can see that from the heading, on 2 September 1996, along with a covering letter.
A It was not faxed to me.
Q No, it was faxed to Dr Mike Thomson.
Q But it was faxed to the unit.
Q I want to ask about particular item 3, repeated metabolic investigations: could there be any metabolic investigations, because it says, “which should include” and I take it from that that does not actually mean “these should be the only ones which should be done”, but it says “which should include”. Could there be any metabolic investigations that could actually be done through the cerebrospinal fluid?
A By “metabolic” we are talking probably about, again, mitochondrial disorders, and certainly one of the tests that is recommended in trying to diagnose mitochondrial disorders is to obtain cerebrospinal fluid by lumbar puncture.
Q Do I take it that even though the letter does not specifically mention lumbar puncture that it could mean that under item 3?
A It could mean that, yes.
THE CHAIRMAN: Thank you. I do not have any further questions but Ms Golding has one more question.
MS GOLDING: You went away to Australia for a year.
Q What were you doing in Australia?
A Paediatric gastroenterology.
MS GOLDING: Thank you.
THE CHAIRMAN: Dr Casson, the Panel members do not have any more questions but counsel may have some, so I will give all of them the opportunity to ask you any more questions.
Further re-examination by MS SMITH
Q In relation to Child 9, Dr Moodley asked you about the follow up on lead: can I just take you to the sequence of letters relating to that? If you go to the local hospital records for Child 9, volume 2, page 164. I just want to follow this through so we have the information, if you would bear with me. I am only referring to the part relating to the lead levels. This is a letter to Professor Walker-Smith from the consultant paediatrician Dr Spratt and he says in the middle two paragraphs:
“As promised I used the opportunity to draw whole blood for additional lead studies and enclose a copy of the laboratory report for further information. It seems the units used … are not exactly comparable to those [referred] to at the time of Dr Malik’s test results last November, but the elevation … seems of much the same order and obviously abnormal.
I wonder, can you confirm that interpretation and say anything about what high levels of trace elements (lead/zinc) in blood might mean in [Child 9’s) case? I am really unsure of what to make of the data. What did Dr Malik have in mind first time around? …”
Then if you go to page 163 Professor Walker-Smith says to Dr Spratt:
“As to his high lead levels, I am puzzled by this. You have certainly confirmed this unexpected finding. The reason for screening for trace elements originally was looking for deficiency and we were not expecting increased levels. Whether high lead is relevant to [his] illness I don’t know, but I wonder if there are any local special factor environmental risks in his case. Does he have PICA?”
Going to page 161, we see a letter from Dr Spratt, the child’s consultant, to Professor at the Metabolic Unit at the Institute of Child Health. He asks about the lead levels (page 162):
“In [his] work-up last November his registrar” – which I assume is a reference to Dr Malik “ – looked at trace metal levels in blood – expecting low or hopefully normal and was surprised to find a very high lead level … No interpretation was volunteered – but I was asked to repeat the test in due course.
I did so in June/July – possibly using different methodology …”
And he said it was high:
“Obviously the search is on for unusual exposure to lead and/or zinc ingestion and, yes, indeed, the family do live in an old house and [child 9] does exhibit prominent PICA – or at least did so until a few weeks ago …
In the meantime I am challenged to say if the high lead and zinc … levels have any likely clinical significance. By laboratory definition they are abnormal – but are they high enough to be toxic? He has long-standing features of severe autism and a history of abdominal pain (and PICA) but no other symptoms and his blood counts [etc] remain remarkable.”
So that was a request by the child’s local consultant to a metabolic expert, Professor Leonard. Then if we turn on to page 157, this is slightly out of sync. This is Professor Walker-Smith’s letter saying:
“Can I suggest that you repeat the blood lead and zinc data. Certainly [Professor] Leonard’s opinion would be helpful. I don’t know what the lead units are but I attach a copy of his print out.”
So that was obviously written before Professor Walker-Smith knew that Professor Leonard had advised.
Then if we go on to page 154: this is Dr Spratt to Professor Walker-Smith:
“I have … heard from James Leonard and enclose copies of our further exchange …
It seems we cannot get the units for blood lead values quite right, but there is probably fair agreement that [his] levels … are moderately raised – if not actually clinically toxic.”
Dr Spratt says he is going to monitor the levels.
Then at page 150 Professor Walker-Smith writes back to Dr Spratt saying:
“Thank you for sending me the details concerning [his] lead levels. I think James Leonard’s comments are extremely helpful.”
The last letter is page 142 ---
MR MILLER: What about page 151?
MS SMITH: I am sorry, Mr Miller …
MR MILLER: 151: sorry, it is out of order.
MS SMITH: At page 142 is from Dr Spratt to Professor Walker-Smith dealing with the lead question, in the middle of the page:
“Unfortunately, notwithstanding what [child 9’s] parents believe he has less preoccupation with PICA over several months his serum lead level has remained raised … slightly higher still! Clearly although on James Leonard’s advice we do not think these levels are clinically toxic their persistence is unsatisfactory and it is time to search out the source of abnormal ingestion …”
Then he goes on to the zinc result and asks whether it could be a source of gut irritation.
I think that is the last letter. Mr Miller will tell me if I am missing one but I think that is the last letter in relation to lead.
I am told there is one more, page 145: Professor Walker-Smith says to Dr Spratt:
“Thanks for your letter. I was very interested to hear the latest about the lead story. I would be happy to see him again. I shall ask my secretary to send a follow-up appointment.”
So that, for the sake of completeness, is the sequence of events in relation to that matter.
I have no other matters, thank you, sir.
THE CHAIRMAN: Thank you. Mr Coonan?
MR COONAN: Nothing, thank you.
THE CHAIRMAN: Mr Miller?
Further cross-examination by MR MILLER
Q Nothing to do with lead, Dr Casson, just two points: you were asked by Ms Golding about how you felt about using children, by implication the children who were coming in to be investigated whose cases you went through yesterday. Did you see it as you using children or investigating and trying to help them?
A Investigation and help.
Q Again, Ms Golding suggested to you that in effect all these children had constipation and again by implication their bowel problems could have been solved by uncomplicated treatment with liquid paraffin: is that correct for these children, did they have simple constipation?
A I think they have constipation.
Q But is that the end of the story? Once you identified the constipation do you have to find out what might be causing it?
A Constipation is a very common problem in paediatric practice, and on the whole these children are otherwise – for want of a better term – well and therefore there is no indication to look further than the fact that the diagnosis is made and instigate treatment.
Q Did these children fall into that category?
A They had other ongoing problems.
MR MILLER: Thank you.
THE CHAIRMAN: Mr Hopkins?
MR HOPKINS: Nothing, thank you.
THE CHAIRMAN: Dr Casson, we have come to the end of your evidence now so can I thank you again for coming and giving us the last two days and this morning. You are now released.
(The witness withdrew)
MS SMITH: My next witness is Professor Salisbury. Before I call him, there are papers which were removed from all the Panel bundles because there were objections, which have now been resolved, and those papers have got to be reinserted. We all feel that it would be more appropriate if it was done in advance of the witness rather than you having to keep putting them in, because there is quite a lot of them. I wonder whether that could be done before Professor Salisbury is called, and therefore I wonder if you would adjourn for a short time.
THE CHAIRMAN: Yes, I am sure that is the appropriate way of dealing with it, so we will now adjourn until 10.50.
THE CHAIRMAN: Ms Smith.
MS SMITH: Sir, before I call the next witness, the Secretary has just asked me to read out to you the documents that have been put back into your Panel bundles so that it is on the transcript. You need not worry about it. As I say, they are all back in your bundles, but they are the following documents: in FTP1, page 70 and page 71-86; in FTP2, page 395-396, 408, 497-500, 617-619, 620, 621-622, 623, 646 and 647-673; in FTP3, page 824-922, 973-1052, 1141-1196, 1197, 1202 and 1220-1222. Sir, with respect to FTP3, you will see that there are some deletions on pages 1144 and 1202, and those simply relate to matters which are wholly irrelevant to the charges that you have to consider and so have been deleted, by agreement with the defence. So those are the documents, sir. If you are happy that I go straight on, I propose to call Professor Salisbury.
THE CHAIRMAN: Yes, indeed.
DAVID MAXWELL SALISBURY, Affirmed
Examined by MS SMITH
(Following introductions by the chairman)
Q Professor Salisbury, could I ask you first of all to give us your full name, please, and your address.
A My full name is David Maxwell Salisbury. My home address is XXX.
Q I think it is correct that you are currently the Director of Immunisation at the Department of Health?
A That is my appointment at present.
Q I want to take you, first of all, Professor, to your CV, and it may be that it is already on the table for you, but you should have some bundles called FTP bundles, and if you go to FTP7.
A Yes, I have that.
Q Your CV is behind tab 1. If I could just take you through the salient points in that. First of all, your present post, which is on page 1, as you have told us, Director of Immunisation at the Department of Health and Visiting Professor at the Department of Infectious Disease Epidemiology at Imperial College. Then you say:
“National leadership for immunisation programme giving direction for research, strategy, policy, vaccine purchase and implementation.”
Does that sum up in a sentence the role that you fulfil as Director of Immunisation?
A Yes, I am sure it does.
Q I think it is right that you are in fact a registered medical practitioner.
A That is correct.
Q If we look at pages 14 and 15 of your CV we see your clinical experience, which culminates on page 15 as Consultant Paediatrician, 1986, at New Cross Hospital in Wolverhampton, is that correct?
A That is correct.
Q Then turning back to page 4, are you the Chair of the World Health Organisation Strategic Advisory Group of Experts to Global Progamme on Vaccines?
A Yes, that is correct.
Q Can you tell us what, in broad terms, does that Committee advise on?
A Yes. This is the top level advisory group that reports directly to the Director General of WHO, and it provides the overview of all of the immunisation work that is undertaken both in Geneva (the headquarters of WHO), but it also provides the leadership for all of the regional offices of WHO. It encompasses work that goes from the research agenda of WHO through to matters relating to programme implementation. It covers all of the vaccines both used in routine programmes and indeed used under special circumstances. The Committee meets twice a year, but clearly we have numerous teleconferences and so on in between. At the end of each meeting I will report directly to the DG and discuss with him or her what are the important issues that are arising. As Chair of SAGE I am automatically an adjunct member of the Global Advisory Committee on Vaccine Safety, which is a slightly separate committee with a different sort of reporting, but nevertheless it is important that there is crossover between the committee that is advising on global policy and the committee that is giving advice on safety of vaccines. I also chair a number of other WHO committees. I chair the Committee on Certification of Polio Eradication for Europe, which makes me a member of the Global Commission for Certification of Polio Eradication. I am a member of the Eastern Mediterranean Commission for Certification of Polio and also the South-East Asian. That is a sort of reasonable resumé of my current WHO involvement.
Q Thank you. I think if we go to your past professional activities, which is on page 5, you advise on immunisation, and have done to national governments and organisations such as UNICEF, and we can see on that page, the second paragraph down, under “Past Activities”, that you have advised numerous governments in relation to their immunisation programmes, is that correct?
A I have, and I continue to do so, and I continue to advise international organisations, foundations such as the Bill and Melinda Gates Foundation, and so on.
Q Do you also lecture nationally and internationally on the subject of immunisation?
A Quite a lot.
Q Are you on occasions also requested to act as referee, and we have heard about the refereeing system for peer review journals, for scientific papers relating to your specialism?
A Yes, I have been invited to act as referee for numerous journals. Clearly I have to be very careful that the occasions on which I am asked to act as a referee do not in any way conflict with the work I am doing, and so there have undoubtedly been occasions when for example I have declined invitations to referee articles because I felt that there was a potential for conflict to be perceived with the interests of my post.
Q I am not going to take you through the details, Professor, but between pages 7 and 13 do we see the details of your own publications, which are widely again on the subject of vaccination of various kinds?
A I mean, that is correct. It is clearly quite difficult in the post that I have to be doing original research, but nevertheless it is an important part of what I and my group do, when we do have important or novel observations, to be able to report them, and we also do quite a lot of publication that is effectively educational.
Q I think also you are Secretary to a committee which again we have heard a little about, and that is the Joint Committee on Vaccination and Immunisation, the JCVI Committee, is that correct?
A That is correct. The Committee has two Secretaries effectively, a Medical Secretary and an Administrative Secretary, and my task is to give the strategic direction for the scientific work that is brought to the Committee. The Administrative Secretary clearly deals with all of the day to day management of the Committee so that it functions in an effective way.
Q The Committee members of that Committee, who are they? I do not mean their actual identities, I mean their specialisms.
A The Committee really spans all of the arena of immunisation and so it has representation from all of the main disciplines that are important from whom we should get advice, so we have everything from primary care, virology, public health, microbiology, paediatrics, community child health, nursing and we have a lay representative as well.
Q The members on that Committee, how are they appointed?
A They are appointed through the NHS Appointments Commission. The process basically is that when we anticipate that a member or members are coming to the end of their term, we then commission the Appointments Commission to start the process of recruitment of new members. That involves widespread advertising through medical journals and in the lay press that we are looking for new members. We specify the sort of qualifications that we expect, that they would be leaders within their discipline that is appropriate. They are asked to submit a detailed CV that includes their justification for their eminence, and also that details why they wish to serve on this Committee. The Appointments Commission then undertakes a fairly straightforward and I think routine process of shortlisting, which is done by a panel who will be then taking part in the selection, and then there is an interview of usually three to four candidates, if that is the number that we have been able to identify through the sifting process. The interviews are chaired by a member of the Appointments Commission. The chair of JCVI takes part if he is available. I have taken part in some of the appointments but not all of them. There is an independent person also who takes part in the appointment.
Q Now, Professor, you have told us you are responsible for the UK’s immunisation programme, and, as you know, that is what you are here to tell us about today in one particular context, and that is the context of measles, mumps and rubella vaccination. I want to ask you to take your mind back, if you will, to the position as it was as you recall in 1986. First of all, were you employed at the Department of Health at that time?
A Yes, I was.
Q As a Senior Medical Officer, is that correct?
Q Can you tell us were there concerns in relation to aspects of the UK vaccination programme relating to, firstly, measles, and, secondly, to rubella, or German measles?
A Yes. The situation was that where measles vaccination was concerned, we did not compare favourably with other industrialised countries. The coverage of measles vaccine was relatively low, it was of the order of 60-65 per cent, we had measles epidemics every other year, and other industrialised countries were doing very much better. The reasons for this were multiple, in part I suspect because of the hangover that had come from scares about the safety of whooping cough vaccine, which had preceded this period, but nevertheless the coverage of measles vaccine was relatively poor. The coverage of other routine childhood vaccines was in the high 80s approaching 90 per cent, so there was a considerable disparity between measles vaccine coverage and that of other countries and indeed other vaccines.
Q Now, can I just ask you, before you go on, you say there were epidemics in alternate years.
Q Were there deaths from measles resulting from those epidemics?
A Yes. There were roughly twenty deaths averaged across the years.
Q You say we did not compare as well as other developing countries---
A No, developed countries.
Q Developed countries, sorry.
A There were developing countries that were doing better too.
Q Well, as far as the developed countries are concerned, who in particular was a comparison being made with at that time?
A Well, the United States was an important comparison, for reasons that I will come on to relating to rubella, but the United states had considerably higher measles coverage, and by that time they were already using MMR vaccine as their routine vaccine.
Q In 1986 in the UK what was the vaccine for measles?
A Well, we were using just single measles vaccine as a one dose programme given to children at around a year to fifteen months of age. We had no mumps vaccination as part of our routine. We had rubella immunisation which was for adolescent girls at around 11-13 years of age, and the programme was also available for women who had been screened in pregnancy and found to be negative to rubella, and they were supposed to be vaccinated after the birth of a baby.
Q Now, if we can just separate them off for a moment. So you are saying as far as the measles vaccine at that time was concerned, it was a single measles vaccine, and the coverage you say was poor comparatively at 60-65 per cent.
A We had far more cases of measles than comparable countries.
Q As far as rubella was concerned, can you help us as to what the most serious implications of rubella are.
A Yes, of course. Rubella infection in a child is relatively trivial. It may go even unnoticed or it may present with just a mild rash and a mild fever. Rubella in a pregnant woman, and particularly in the early part of pregnancy, is devastating, and the consequences, there can be foetal death, or the baby can be born with multiple handicaps affecting many different systems, affecting the brain, liver, spleen, heart, bone marrow. Name the system and you can find damage pretty much from congenital rubella. Deafness is a common outcome, particularly at the very early part of pregnancy.
Q If you can just explain to us, vaccinating the child against measles is to stop what?
A Is to stop the child getting measles, but there is a secondary issue too. Not only are you stopping the individual child from getting measles, but your objective is to stop the transmission of measles so that children who have not been vaccinated are themselves protected so that children too young to be vaccinated are protected by the benefit of the community around them.
Q In 1986, as far as rubella was concerned, was the aim of vaccination to stop the child getting rubella?
A It is very important to understand that the main driver for the change to MMR in 1986 was rubella. This was the real focus of concern. Measles – clearly we needed to do better, but it was the whole of the rubella strategy that was coming under examination and that the decision to change was actually hanging on.
Our rubella strategy at that time was, as I have said, the vaccination of adolescent girls. If you vaccinate adolescent girls you have to accept that rubella virus will circulate freely amongst children below the age of the recommended vaccination. If you have a programme that is going to vaccinate girls at 11-13, you know full well that boys and girls who are younger are going to catch rubella. That is on the basis that this is, by and large, a trivial short illness with spontaneous recovery in those ages.
You depend greatly on protecting the individual through this strategy so that the individual girl is protected and therefore by the time she becomes a woman who is pregnant she is immune to rubella and therefore, if exposed to the virus, does not catch it. That is an accepted strategy for rubella and the prevention of congenital rubella syndrome. It is directed essentially at preventing congenital rubella syndrome but it is not a perfect strategy because if a woman is vaccinated and, for instance, the vaccine does not work, or simply does not get vaccinated, she is at risk and she is at risk if rubella is circulating amongst children.
We knew that we had made an impact on congenital rubella through the selective programme that we had implemented, that was clear, but we had not made as big an impact as others had been able to achieve using a universal immunisation programme. We knew that because we still had cases of congenital rubella and we had of the order of 200 terminations of pregnancy because women had been exposed to rubella in their pregnancy and that is a consequence that you know you will have to face with a selective strategy.
Q You have mentioned the experience in other countries, in the US in particular, in relation to measles. Was the US experience also different in relation to rubella?
A Yes, it was. They had not used the selective approach that we had used. They had used the universal immunisation approach. The reason for choosing one or the other is essentially your coverage of measles vaccine. Measles vaccine is the sentinel that will tell you what your coverage will be of rubella if you add it to the measles vaccine and give it at the same time. In the United States they had high coverage with measles vaccine and therefore adding rubella to it was a safe and effective thing to do. If we had added rubella to our infant measles programme we had low coverage relatively of measles and this matters. The reason that it matters is that if you vaccinate with rubella at low coverage, or at a relatively older age in childhood for both sexes, you do not achieve interruption of transmission of rubella. You push down the circulation through your vaccination but you do not interrupt it. That means that individuals who have not been vaccinated get older and older still not exposed and they then can be exposed as young female pregnant adults and you thereby increase the risk of congenital rubella syndrome. Low coverage of rubella in childhood pushes down the circulation but does not stop it, lets people get older and older without being infected and then it increases the risk.
In the mid 1980s we had this dilemma of wanting to do more about preventing cases of congenital rubella syndrome but measles vaccine coverage was not yet high enough and it was only in around 1985/86, when there were quite a number of scientific meetings to review this, that it became clear that measles vaccine coverage was now reaching the level when it would be safe to change strategy and move to the use of MMR vaccine.
To that end we commissioned mathematical modelling. At least two groups of mathematical modellers were asked to model what would be the consequences of changing at that time from a selective to a universal rubella programme. Because people very rarely agree fully, we then got a third group to review the work of the first two groups to come to a view as to where the strengths and weaknesses were in the arguments and all of this was shared with the Joint Committee on Vaccination Immunisation. In 1986 the evidence was reviewed and believed that this was now the right time to change from our selective to a universal – in fact, we actually kept both programmes going and it was extremely important that we kept both programmes going. Had we just introduced MMR and given up the selective programme we would have had cohorts of girls who had not been protected so we had to keep the selective programme going until we knew that the cohorts who had had MMR had indeed come through to that sort of age.
Q You have described the consultations you embarked on and the independent mathematical modelling that you had done. Was that all information which was shared with the Joint Committee on Vaccination and Immunisation?
A Yes. The sequence of events was that, I think in very early 1986, there had been a meeting at the Public Health Laboratory Service to bring together a great deal of the science on this strategic direction and that was then reported to the Joint Committee by I think Dr Christine Miller who was an epidemiologist working at the Public Health Laboratory Service. She reported on the meeting that they had organised to review the scientific evidence and the Joint Committee was also given the results. In fact, the mathematical modellers came and presented their information at the Joint Committee hearing.
Q I am going to take you to the minute in a moment but I want to ask you, first of all, that presumably the Joint Committee have to reach some consensus conclusion. Do they then recommend to your department and to the government the appropriate way in which the matter should go forward?
A Yes. The process is that the committee clearly will discuss and debate any particular issue. The role of the secretariat is to provide information but we take no part in the decision-making of the committee. The chairman will hopefully achieve a consensus amongst the members and that will then become a recommendation that the committee will make to the department. The process then is that that recommendation is shared through the Chief Medical Officer and to ministers and ministers will make a decision about whether they will accept the recommendation. There has been almost universal acceptance of recommendations.
Q Please take out bundle FTP1, page 4. Page 1 is the start of the minutes, Professor. You have a long index and then you should get to page 1 which is the JCVI minutes of the meeting held on Friday 7 November 1986.
A That is correct, yes, I do.
Q These bundles, as you will discover later on, are chronological. This happens to be the first document in the first bundle chronologically. This was a meeting at which you were present, is that correct?
A Yes, I was.
Q Going to page 4, we see the recommendations.
“It was recommended that the existing rubella programme be expanded by the use of MMR vaccine in the second year of life. Surveillance both serological and otherwise would be needed to identify any possible effects that such a change of policy would have on the incidence of mumps. An acceptance rate in excess of 68 per cent (the 1985 figure for measles vaccine) was an essential requirement. It was agreed the change was necessary.”
Then there is Dr Miller’s paper on rubella as you already referred to. We can see, and you can be asked about it if necessary, the various comments and concerns about MMR and when it was relevant for that change to be made, is that correct?
A Yes, that is correct.
Q That was the recommendation. Was that in fact implemented?
A Yes, that recommendation was taken forward to ministers and was accepted and we then started the work up to introduce a new vaccine and clearly the timeline that we had available was approximately less than two years to work up the introduction of a new vaccine. It is a bit like an iceberg: the recommendation is the bit above the water and the amount of work that has to be done is the bit below the water.
Q What was the actual plan to be? It was to implement a programme of MMR for what age children?
A The recommendation was that MMR would essentially replace measles vaccine given to children at around 13-15 months of age, and again it comes back to the importance of rubella immunisation, we also realised that there were children who would have had measles vaccine who were going to be going into school fairly soon but who had not had rubella vaccine and it was important to try to protect those children before they had an opportunity to catch rubella. Therefore we recommended that health authorities should put in a catch up programme so that they offered a dose of MMR to children even if they had had a previous measles vaccine before they went into school and the opportunity to do that was offered at the time of their pre-school booster.
Q You have said that the recommendation was the tip of the iceberg. When were you actually in a position for that programme to commence?
A That programme started in the autumn of 1988.
Q As far as the results of the introduction of that programme, were they apparent and what were they?
A Yes, we saw the results very quickly. We saw gratifyingly that coverage rose; that the introduction of a new vaccine was greeted very positively and so immunisation coverage rose by the order of 10 per cent over a very short period of time. We saw that measles notification – and we had also introduced probably a world first in surveillance of measles through the use of saliva as a way of testing for measles – we saw that confirmed cases of measles fell extraordinarily rapidly and this was very, very gratifying. We saw an impact on mumps and cases of mumps were again disappearing rapidly. Hospital admissions for mumps – meningitis, mumps encephalitis – which had previously been running at about 1200-1400 a year, again pretty much disappeared. Looking at rubella is more difficult because of the difficulty of diagnosis. We saw that there were reductions in the numbers of cases of congenital rubella syndrome but we also saw that there were, very importantly, reductions in the numbers of cases of rubella in pregnant women and most importantly they were most notable in women who had got more than one child. So women who had got previous children were far less likely to catch rubella in pregnancy than they had been before and the reason was that they were not catching rubella from their own children or from their friends’ children. This was an extremely sensitive way of looking at the impact of the introduction of MMR. We also saw that terminations of pregnancy went down to tiny, tiny numbers.
Q Can you give us a rough idea of the number of terminations there were prior to this programme being introduced?
A Yes, it was at least 200 a year. I would have to go back and check that data but it was of that order. That is terminations of pregnancy because of rubella infection in pregnancy, not terminations of pregnancy.
Q As far as they are concerned you say that they were reduced to a tiny number.
A Yes. I think all the parameters were showing that this had been a very successful introduction of a new vaccine.
Q I wanted to ask you about a specific matter relating to a specific strain of the mumps vaccine. Did a problem arise in relation to that in 1989/1990?
A Yes, it undoubtedly did. We were aware from a publication that had come from Canada that they had reported I think it was seven cases of mumps virus, and it was probably vaccine virus, meningitis that was occurring in recipients of one particular sort of MMR vaccine.
Q From the mumps component?
A From the mumps component. That was fairly clear for a number of reasons. The evidence that one of the other vaccines did or did not do this was really quite difficult to obtain and I am happy to talk about that. Nevertheless, we were aware of this and we made sure that surveillance was in place so that if it was happening here we would detect it. The frequency of this event that was reported in Canada was of the order of one in 80,000 vaccinees and the presenting feature of this was usually a febrile convulsion, which is a common event in childhood. The frequency of febrile convulsions after measles vaccine is 1 in 1,000, so this was a mild, self-limiting event that was occurring 1/80th of the frequency of an known and accepted event with measles vaccine. We nevertheless made sure that we had surveillance in place that would identify this if it were occurring and indeed cases did start to be detected.
The surveillance that we put in place was through the British Paediatric Surveillance Unit which had hitherto been an extremely effective way of detecting rare events that paediatricians were then able to share and investigate more carefully. This was not successful and the rate that we were detecting from the BPSU was of the order I think of 1 in 180,000 cases per doses. This did not fit with either the Canadian experience – it was different – and it was then apparent that this was quite different to what was being picked up in Japan where not the same vaccines but similar vaccines were being used. We put in place many other investigations that were necessary to try to establish if this was related to one of the manufacturers’ products, two of the manufacturers’ products or three because we had three MMR vaccines in use. We also had to establish that the immune effect, the protective effect, of the different mumps viruses was the same because, if the protective effect was different, and one of the sorts of vaccine was less effective then the other, you then have to balance the risks of using a less effective vaccine against the disadvantages of a higher number of adverse events and the preliminary data suggested that there was a difference in the immune responses and that the Urabe vaccine, which was the one that was causing the problem, did appear to have better immune responses.
That required further investigations to try to find out if that was correct. Those were done at the National Institute for Biological Standards and Control using more sensitive and more specific tests of immune responses and much of this is published in fact. The outcome was actually that there was a recommendation that you could seriously consider a more immunogenic vaccine against the defects of the reactions, but further surveillance revealed that actually the real rate of adverse events was of the order of 1in 7,000-9,000, which was much closer to what was being seen in Japan. Once all of this information came together and the surveillance was showing us very clearly that this was the correct rate, that it was not just happening with one of the three vaccines, it was happening with two of the vaccines but not the third, we then took action.
It was important that we had the data because, for example, one of the manufacturers initially had the view that their product was produced quite differently, that is their mumps vaccine, and therefore why should they be in the same problem as the other product. So, we had to establish that it was clearly two of the products and not the third and, once all that information came together, and not only did we have the information but we had brought the manufacturers in and we had gone through all of the data with them and told them that we felt that this was not a sustainable position, I went to the United States and reported on all of this to the manufacturer of the third product because, although they had no problem in this regard, they were going to face an intense demand for their product and they needed to understand the grounds on which we were taking the action.
At the very end of August/early September, we issued a Chief Medical Officer letter that we were going to replace all of the Urabe MMR vaccine and only use the alternative US strain, the Jeryl Lynn strain. We reported this to the European chief medical officers in order that we could share this information with them and we reported it to the World Health Organisation. Interestingly, not all of our European colleagues necessarily believed us and some of them continued to use Urabe-based MMR for a considerable period afterwards and it has actually continued to be used in other parts of the world up until fairly recently.
Q Has it been used by the NHS in this country since that incident?
A No. We made no further purchases of Urabe-based vaccine after 1992. We relied on just one vaccine, the one from the United States, for several more years. This is not an ideal situation. We are uncomfortable when we rely on supplies from just one manufacturer because, if they have problems, you have effectively no supplies. A second MMR came on to the market with a very similar mumps strain to the US one. We put in place again heightened surveillance, laboratory-based surveillance, so that if there was any hint that there were cases of mumps meningitis occurring with that strain, we would detect them and none have been detected.
Q Forgive me for underlining it, professor, but remember that the Panel is hearing all this for the first time. All those concerns relating to the Urabe strain, as you put it, relate to the mumps component of the MMR?
A Absolutely. There was no issue about the safety of the measles component or the safety of the rubella component. We acted as quickly as we could to swap over the vaccines and in fact this episode created no dent at all on the immunisation coverage.
Q I want to turn if I may, because this is related to some degree, to a particular vaccine campaign in 1994. I think it is right that preparations for a special campaign began in 1992; is that correct?
A Yes. In 1992, we were clearly pleased with the impact that our MMR programme had had to date in pushing down the circulation of measles to very low levels but managing an immunisation programme should not be reactive, you actually should be proactive. We had in place surveillance that would anticipate problems rather than necessarily tell us that we had problems. That surveillance was, particularly in this regard, the sero-epidemiological surveillance undertaken by the Public Health Laboratory Service. This involves collecting specimens that are taken for routine purposes across all the age groups and you then analyse ---
Q Specimens of blood?
A Yes, specimens of blood that are taken for routine purposes and some of that sample is then used to measure, for example, measles or mumps or rubella antibodies and, by doing this, you can look to see whether you have a fully protected population or whether you have gaps in your population protection. If you have gaps, those people in those gap populations are at risk. Measles is enormously transmissible; it is an extraordinarily effective virus at transmitting from person to person. So, if you have susceptible populations, they are at risk.
Q Did your sero-epidemiology make predictions in relation to a particular area of predicted susceptibility?
A Yes. What we could see was that, up to the age of five, we had high population protection. There were high levels of antibodies across those age groups because they were recipients of MMR vaccine which we had been administering at high coverage. In the age group 5 to 16, we saw that there was a window of susceptibility, that the immunity across that age band was not as high as one would have wanted. The reason for this was that these were the graduates from the previous low coverage measles vaccine programme – they had gone through the measles vaccine programme but not necessarily been vaccinated – and because we had pushed down the transmission of measles, they were not getting infected. So, here we had a group aged five up to 16 who, if measles was introduced into that population, would form the focus of an epidemic and the number of cases were going to be of the order of 150,000 amongst school aged children with an estimate of around 150 deaths.
Q That was obviously a serious situation were it to arise. By 1994, had that predicted epidemic actually arisen?
A No. We saw the beginnings of reports coming from the north of England because the surveillance for the Public Health Laboratory Service is in England and Wales. We started to pick up small numbers of cases being reported in the north of England and they were particularly again in school aged children, exactly the age that we worried was going to be the focus of an epidemic. When we then started discussing this with colleagues from Scotland, they disclosed that they already had ongoing measles transmission and I think they had had something of the order of 80 hospital admissions in Glasgow particularly amongst school aged children. So, the reality was actually coming true.
There is little point running a vaccination campaign after an epidemic because everybody has been naturally vaccinated. The skill is to make the judgment of the risk and do it before an epidemic. The reason is to prevent. Therefore, our judgment – and this was supported again by mathematical modelling and the expert opinion and you have the papers of the JCVI – was that we should introduce a campaign. We then clearly had to discuss what vaccine to use. We knew that this group had not been protected against mumps and we knew that certainly the boys had not been protected against rubella and nor were they going to be. The vaccine of choice was MMR. So, in an ideal world, we would have vaccinated in that campaign with MMR.
Q In very broad terms, how many doses were you anticipating needing?
A It was of the order of eight million but eight million doses of MMR were not available.
Q What was the reason for that?
A They were not available because we had effectively changed the market. By our experience with Urabe vaccine, there was now only one manufacturer who could provide MMR and they had no spare capacity. We clearly went to them and said, “If we needed eight or nine million doses of MMR could you provide it?” and the answer was a very clear “no”. Failing that, we went back to the JCVI and said, “If we can’t get MMR but we could get MR, would that be acceptable?” The reason why we could get MR was clearly that the manufactures had M, measles, and they had rubella vaccine but they did not have a suitable mumps vaccine.
Q We can see what the JCVI had to say about that if you would turn in the same bundle, FPT1, to page 23 and go to page 24. We see that these are the minutes of a JCVI meeting on Friday 5 November 1993 and, by this time, you are listed as the secretariat with one other secretary; is that correct?
Q Would you turn to page 31 of that, please, where we see at paragraph 7.2 a report that was presented, entitled “Interpreting the serological …” that is the blood testing, surveillance that you have told us about using mathematical modellings and the implications for measles and rubella vaccine strategy. Then, on page 32 at paragraph 7.4, a report about immunisation against measles and the catch-up programme you have described amongst those identified as being susceptible, namely school children. Then the conclusion on page 33,
“As a result of the above discussions, the Committee both recognised the risks of a measles epidemic within the next few years and also noted that the present measles immunisation strategy would not eliminate measles nor prevent such an epidemic. The Committee supported both the proposed school-based immunisation campaign and the efforts to prevent the re-accumulation of susceptibles, once measles virus transmission had been interrupted, by the introduction of a two dose unselective immunisation strategy”
and is that two dose a reference to the MR in the way you have explained?
A No, it is not. The MR situation was effectively a one-off because we knew that we were likely to have a significant epidemic and we needed to deal with that. This is, as it were, the lead in to what becomes policy subsequently. The reason for this is as follows. Your first objective in using measles vaccine is to achieve very high coverage with one dose in order that you can do your utmost to reduce the transmission of measles down to very low levels. However, it is not perfection. If you have 90 per cent coverage with measles vaccine, you vaccinate 90 out of 100 children, that is a reality because some will be contra-indicated, some will not be vaccinated and, for whatever reason, out of 100 children, you vaccinate 90. So, you know that 10 per cent of your population you simply have not protected. Vaccines are not perfect and, if you took as a figure of the effectiveness of the vaccine again at 90 per cent, which is reasonable for measles vaccine, you had 90 per cent of your children vaccinated with a 90 per cent efficacy vaccine, so you only have 81 per cent of your children actually immune.
Each year, 20 per cent of your target children will accumulate each year and they have not been protected. You may have vaccinated some of them but they are not protected. As each year goes on, you will have 20 per cent, 40 per cent and so on of a birth cohort. After about five years, you will have the equivalent of a whole year’s worth of children who are not protected. This drives international measles immunisation strategies. There are two ways you can deal with this. One is, every four years you can introduce a new campaign. So, every four years, you go in and campaign and you vaccinate everybody from one to five. That is done and that was pioneered in the English-speaking Caribbean where it was hugely effective; it actually got rid of measles in the English-speaking Caribbean and it was then used throughout Central and South America equally effectively. The alternative approach is, if you do not want to go in and campaign every roughly four years, you introduce a second routine vaccination at around aged four. So, children have their first dose at aged one and then they come and have their second dose when they are aged about four. Those children who are already immune will make no difference – I will come back to that in a moment. The 20 per cent who were not immune you will make immune. So, you have now got rid of the accumulating susceptibility that you otherwise would have carried forward. So, a routine second dose takes out your accumulation of susceptibles
In terms of giving a routine second dose, as a paediatrician, I could go on to a children’s ward and, if I had been vaccinated and a child coughs all over me with measles virus, it does nothing because I am immune. That is the purpose of being vaccinated. If I was not immune, even if I had been vaccinated, I would get measles. The fact is, children can cough all over you every day and, as paediatricians we probably experience that, and, if you are immune, you are immune. So, a routine second dose clearly benefits those who are susceptible and does not do anything to those who are already immune.
Q That is very helpful, thank you. I want to take you back a step. It was my fault because of the question I asked you because we did not quite finish the situation in relation to the MR campaign, that is the campaign that you told us about using MR because of the Urabe’s strain, mumps having been eliminated, there was not enough of the MMR for the school-age children. Was that campaign called “Operation Safeguard”?
A Yes, not by me.
Q But that is what it was known as, is that correct?
A That is correct.
Q That was a campaign using simply MR, measles/rubella, for those children aged 5 to 15 – I am just reminding the Panel because, as I say, I took you on when you were in the middle of your evidence about it – children 5 to 15 who had missed out, as you have explained.
A Well, all children 5 to 15.
Q Yes, school-age children. That was in the hope that would avert what had been predicted as a possible measles epidemic?
A Yes, that was the purpose of the campaign and it was amazingly effective in achieving just that, we did not have a ---
Q I was going to ask you, yes.
A The only test of a mathematical model and a prediction is to let it happen and so the best interpretation is that we had no cases of measles, and it was extraordinarily effective at both preventing an epidemic and actually pushing transmission of measles and rubella even lower.
Q After that campaign what was the effect on cases of wild measles, natural measles, in this country?
A We eliminated measles and against the criteria that were used, for instance, in the United States when they announced that they had eliminated measles, we had eliminated measles. We had no cases of domestic transmission of measles. We had measles coming into the country occasionally and we would identify sporadic cases but they did not spread. There was no ongoing transmission. We were able to start to tell this because of the improvements in molecular biology that were telling us that the previously reported strains of measles that were occurring in the UK were no longer circulating and the cases of measles were coming from imported strains.
Q In other words, coming in from abroad?
Q What about rubella?
A Again, congenital rubella virtually disappeared. We had years of either zero – and I have to say we have extraordinarily sensitive surveillance for congenital rubella syndrome done through the British Paediatric Surveillance Unit and congenital rubella cases themselves either disappeared or were again associated either with women who had caught infection whilst abroad or who had come from abroad and had never been protected against rubella.
Q Just so we understand the complexities of this, professor, that these children, of course, were not vaccinated for the third part, namely the mumps part, because they were just having MR, did that in fact have an anticipated effect on mumps?
A Yes, we were clearly concerned about that. The ideal would have been to revaccinate throughout that, or vaccinate throughout that cohort with measles, mumps and rubella. We knew that we were not dealing with mumps for that 5 to 15 year population, and that it had the potential to be a millstone that would cause problems in the future, and, indeed, it did when starting about three years ago and running through to about one year ago, we had an extremely large number of cases of mumps and those cases of mumps were occurring exactly in that cohort of people who had gone through the MR programme, had not been exposed to mumps because it was not circulating, and were vulnerable, and, indeed, caught mumps. There were some cases at the same time as that mumps epidemic in young children whose parents had refused to have MMR.
Q You have dealt with the second MMR vaccination programme, helpfully, and I just wanted to refer you to one further set of JCVI minutes in relation to that, which is at page 71. If you go to page 72, these are the minutes for Friday 5 May 1995. We see again you as one of the secretaries under the heading “Secretariat” and if we go to page 82 we see an agreement at the bottom of the page, both in relation to the catch-up programme which we have discussed and to the introduction of the routine pre-school booster, in other words the second dose of MMR, is that correct?
A Yes, that is correct.
Q “The pragmatic grounds for the catchup programme were strong. Incidence of disease was low but a one-off catchup programme relatively inexpensive. The committee agreed that the catchup was necessary to prevent the re-establishment of a potentially susceptible cohort.”
So that is the MR programme.
A No actually it is not.
Q Is it not?
A No, it is not quite. What it is is to make sure that the children who have come after the MR programme get their second dose as well as it being introduced into the routine thereafter. Let us just say, for example, we make a recommendation that in a year’s time we will introduce a routine second dose for children aged four, but that means that over this year there will have been children who by next year will have gone beyond that line in the sand and therefore what we were talking about was making sure that they were not disadvantaged and that we would catch up that group who between the MR programme and the start of a second dose were not – they did not fall off the end of the pier because everything had moved forward.
Q And then we see the introduction of a routine pre-school booster with MMR vaccine:
“The committee agreed that the introduction of a routine pre-school booster and that, based on scientific grounds and evidence of the need for measles, mumps and rubella boosting, this should be MMR.”
A That is correct.
Q I want to ask you just to distil what you have already explained, professor, in relation to the distinction between MR and MMR. First of all, did it come to your attention that there were a firm of solicitors looking into the possibility of claims in relation to the MR vaccine?
A Yes. We picked up information that was widely circulated from a firm of solicitors, I think called Dawbarns, that they clearly were interested in clients who believed that their children had suffered as a result of the MR campaign: to put it into context, if I may.
Q Yes, please.
A There are always adverse events – and I use the word “events” rather than “reactions” – to a degree reported after immunisation and we monitor those. When you run a campaign you expose a very large amount of vaccination over a very short period of time, and therefore you have to be aware of what the consequence of that will be on adverse event reporting. The rate at which an adverse event occurs is not different in a campaign doing routine use. If the rate of an adverse event is one in a thousand in a routine programme it will occur one in a thousand in a campaign, but because you do the campaign in a very short period of time and you do many, many, many thousands in a short period of time the absolute number will be high, and therefore when you run a campaign you have to be aware that there will be attention on adverse events and safety issues and although the rate is no different to the rate in routine use – and actually there are reasons to argue why it could be lower, but nevertheless, the absolute numbers may be large, and therefore we knew when the MR campaign was run that there was certainly interest in the adverse events that were reported.
Q Was it your understanding originally that it was the MR vaccine which Dawbarns were investigating, rather than the MMR vaccine?
A Based on the Dawbarns’ fact sheets that we saw, that appeared to be the interpretation.
Q As I say, bear with me because I understand you dealt with this in some detail but I want to distil what you have said: are the children who received the MR different from those who received MMR?
A Yes, absolutely so. The MR campaign was run involving children who in 1994 were between 5 and 15 years.
Q How long was that campaign run for?
A About six weeks. We only used MR ever in our programme between November and December. There was a bit of overrun in some schools into January but MR was only ever used in our programme in the period of the MR campaign and these children were not the routine MMR recipients.
Q So it was for six weeks, and as you have already told us it was school-age children 5 to 15. As far as the MMR is concerned, again you have already dealt with this but just to summarise, how long a period has that vaccine been used for, that triple vaccine?
A The first dose programme was introduced in 1988. The effective second dose was introduced in 1996, and I have mentioned a relatively small amount of catch-up that we did.
Q So in broad terms, just leaving aside the catch-up for the moment, at what age was MMR being given to children?
A It was being given to them at 13/14/15 months was the recommended span for the first dose, and the recommendation was that it would be given for the second dose with their pre-school booster, which was ideally given between three and a half and up to five years, according to local circumstance.
Q Would you expect anyone with a research interest in vaccines to know that these two vaccines were given to different cohorts of children?
A You cannot confuse MR with MMR. If you write “MR” you mean measles/rubella. If you write MMR, you mean measles/mumps/rubella. We are very specific in the terminology that we use to describe vaccines. If we want to talk about diphtheria, tetanus, pertussis vaccine, we abbreviate that to DTP. If we want to talk about the acellular form of pertussis vaccine we would call it DTAP and we would call the whole cell CTWP. If we are talking about diphtheria we would use a capital “D” to talk about high dose diphtheria vaccine and if we used a lower case, little “d”, we would be talking about low dose diphtheria vaccine. We are extremely specific in the use of abbreviations so that we convey exactly what vaccine we are talking about.
Q If I can just stop you there, professor. You are talking about “we”. Can I ask you, if you have somebody who is a researcher with an interest in vaccination, who had formulated a research protocol relating to measles or MR vaccination, would you expect them to know that they were different from MMR?
A I would offer that if they did not they should not be doing what they were doing.
Q Would you turn briefly to the scientific protocol which you will have seen before in FPT3 at page 1146, which is headed “Proposed clinical and scientific study”, just to orientate you, and is entitled “A new syndrome, enteritis and disintegrative disorder following meals and measles/rubella vaccination” and if you would and at page 1149, the introduction:
“There are indications of the emergence of a new syndrome comprising disintegrative disorder and a possible enteritis associated with vitamin B12 deficiency. The syndrome has been linked – anecdotally but consistently – with either measles or measles/rubella vaccination. It appears to occur in previously well and developmentally normal children following exposure to these vaccines.”
And then at page 1153 we see the working hypotheses set out, and I am not going to go through them with you but we see the introductory paragraph:
“The possible link between an environmental insult (measles/rubella vaccine) in a previously healthy child, who may be genetically susceptible to responding inappropriately to the virus via abnormal complement regulation, and the subsequent development of enteritis, Cbl-deficiency and disintegrative disorder, permits several working hypotheses to be proposed.”
And then at 1157, the “Practical issues” and we see in the third sentence:
“However, it is essential that we characterise as comprehensively as possible, the pathogenesis of this condition – control of any underlying intestinal immunopathology may open up new therapeutic avenues for the treatment of affected children. Our ability to confirm or exclude a role of measles or measles/rubella vaccine also has major implications for public health.”
I have to extract, there may be more, the references to the vaccines in that protocol, and I want to ask you, do you understand that protocol to be making any reference to research on MMR vaccine?
A I found this protocol extraordinarily surprising when I first saw it because it made no reference to MMR.
Q That is really what I am trying to extract from you. Do you understand it to be involved in research on MMR at all?
A No. Nowhere does it mention that.
MS SMITH: I am going to turn on to a topic which is related to that but which goes back chronologically to your knowledge and involvement in Dr Wakefield’s research in general terms. Sir, I see it is nearly 12.50. I do not know, would you like to break and then start again a little early or whether you would like me to begin. This, as I say, is related, obviously, to the document we have just been looking at but it requires going through numerous documents and it is a relatively new subject.
THE CHAIRMAN: I think now would be a good time for us to adjourn and to resume at 1.45 if that is acceptable to you.
We will now adjourn, but, Professor Salisbury, you are under oath and in the middle of giving evidence so please do not discuss this case with anyone during the adjournment.
THE CHAIRMAN: Good afternoon, everyone. Just before we start, I believe, Ms Smith, and I am saying that to all the defence counsel as well, I believe you are aware that we are rising at a quarter-past four this afternoon.
MS SMITH: Yes, we were told that, sir. Thank you.
THE CHAIRMAN: I suspect that all the defence counsel are aware of that as well. Good. Ms Smith.
MS SMITH: Professor Salisbury, I want to ask you about your first contacts with Dr Wakefield, and I think it is right that they were in the autumn of 1992. Were you Principal Medical Officer at the DOH at that time?
A Yes, I think so.
Q Before I actually look at the correspondence, I want you to deal first of all, if you would, with the position with regard to correspondence which is sent to the Department of Health generally. If it is correspondence which is sent to the CMO, who was at that time I think Sir Liam Donaldson---
A No, not then. It was actually Donald Acheson, I think, probably just about. It was probably changing over then from Donald Acheson to Ken Calman, but I would have to check that.
Q Thank you. Well, whatever his identity, if it is sent to him as the Chief Medical Officer, how is that dealt with within the Department?
A Well, correspondence that clearly goes to a named individual will go direct to that person. Correspondence that goes to the Chief Medical Officer will be dealt with according to his office, who will decide whether they want to get a contribution to a reply from one of the departmental specialists or a generalist, or the reply will be generated by the CMO himself. Similarly, correspondence that goes to ministers will again go down usually through the departmental officials for advice on a reply, and they will again seek expert input if that is appropriate.
Q If it is relating to vaccination issues, would it come to you in accordance with that---
A Over time it would have depended what the issue was and who was available. If it was one of the vaccination topics that I personally did not cover - for instance a colleague who was dealing with tuberculosis would have picked up correspondence specific to that, whereas work that fell to my area would be sent to me.
Q Would your area have encompassed MMR at that time?
A Yes, it would.
Q If we could go, please, in your FTP Volume 1 to page 12. This is a letter from Dr Wakefield direct to you dated 2 October 1992, and if I can just run through it, Professor, and then I will ask you some questions about it afterwards.
“Further to our telephone conversation on Wednesday 23rd September 1992, I am writing to clarify the position with regards to the potential aetiology of inflammatory bowel disease and the role of measles virus. Three years ago we started work on the pathogenesis of Crohn’s disease. Our work confirmed the presence of an ubiquitous vasculitis in this condition which was far more frequent than had previously been appreciated in histological evaluation of tissues. The basis of the pathogenic process of Crohn’s disease is, we believe, a granulatomous vasculitis which progresses to ischaemia and ulceration of the overlying mucosa.
Our interests were focused subsequently upon agents capable of a persistence in vascular endothelium”.
He then goes into the detail of that, and says:
“At the top of this list were ….. [included] measles, mumps and parainfluenzae virus. The behaviour of measles virus during the acute infection, its localisation to the gut, and its subsequent capacity to produce panenteric inflammation and ulceration meant that it was a particular interest to us. We examined Crohn’s disease and tissues from ulcerative colitis and non-inflammatory control patients by in situ hybridisation and immunochemistry as well as ultrastructural analysis. These three techniques have confirmed in the 24 Crohn’s patients ….. to date, the presence of a paramyxovirus which has both the genetic and protein characteristics of measles virus. The localisation of the virus was to the granulomas and secondary lymphoid follicles, hallmark lesions of this condition.
Of particular [interest] to us is the real increase in the incidence of Crohn’s disease in children over the past 15-20 years. When one looks at the rate of uptake of the measles vaccine during this period there is a similar upward trend between these two sets of data.
The purpose of my phoning you to discuss this was to forewarn you that this will be the first question that is raised following publication of the paper. Although this question has not been addressed in the publication itself, obviously we will need to do this in the very near future. My concern is that although measles, and in particular the vaccine may ultimately have no association with Crohn's disease whatsoever, what will be picked up by the press is the apparent association between the increasing incidence of disease and the vaccine. Therefore I think it would be imperative for us to meet in the near future to discuss the way forward.
Over the past three years I have put together a team of some 50 individuals with expertise in various aspects of inflammatory bowel disease, virology and molecular biology and we are now in a position to answer any questions that might be raised. However, adequate funding is crucial to this research programme and this is an issue which must be discussed when we meet.”
Now, Professor Salisbury, first of all, it seems that that letter followed a telephone conversation between you. Do you have any recollection as to that, as to how that came about?
A How the telephone conversation came about?
A It was an impromptu call that I received from Dr Wakefield.
Q The letter is about the possibility of measles virus playing a role in Crohn's disease, is that correct?
A That is correct.
Q We see in the last paragraph touching on the possibility of the vaccine during that period playing a part in that. The letter expressly tells us that that issue is not in the paper but there is a fear that the press may pick that up. Then there is a reference we see to funding, and the adequacy of funding for Dr Wakefield’s research group. Did you understand that to have any relevance, the issue of funding, to the rest of the letter?
A Well, I am not sure about relevance to the rest of the letter, it was in the letter. He was telling me about some of his work. He was saying what was going to be in a forthcoming paper. He said what was not in the forthcoming paper but somehow this would become a matter of public interest, which was in itself odd – if it was not in the paper, why would it if it was not created? – and he was saying that funding was crucial for this research programme, but the Department of Health normally would not be funding this sort of biomedical work. This is the sort of work that normally the Medical Research Council would fund.
Q Now, did the contents of the letter in broad terms mirror the telephone call that Dr Wakefield had made to you? I mean, was it in relation to the same issues?
A Oh, I think so, but, I mean, that is a fairly distant memory.
Q Absolutely. We see your reply, which is on page 14, and you wrote back on 4 November 1992, saying:
“Dear Mr Wakefield
Thank you for your letter of 2 October explaining about the research that you are carrying out on Crohn's disease.
I think it would be interesting to meet to hear a bit more about your research and I will get back to you shortly to try to arrange a meeting.”
Did that response, that you thought it would be interesting to hear what Dr Wakefield had to say, did that accurately and genuinely reflect your state of mind at that stage?
A Yes, I think it accurately reflected my state of mind. I found his letter, I think, sort of challenging because of some of the concepts that were within it. The fact that he was raising the possibility that measles virus was causing Crohn's disease was interesting. There had been other examples of conditions where measles was blamed for causing them and they had been found to be wrong. The timing was interesting in that we were on our way to eliminating measles at that time, and if that was the case, measles being the cause of Crohn's disease was in a way a somewhat historic interest. So the letter was a slightly odd letter, but clearly, yes, it was important to acknowledge it. I have to say that it arrived, as you probably realise from what I said earlier, when we were pretty busy.
A At that point in 1992 we were just in the process of exchanging Urabe vaccine for Jeryl Lynn vaccine. What I have not mentioned was at exactly the same time we were running a campaign to introduce a vaccine against meningitis, which we had launched. We were introducing a new way of distributing our vaccines and a new way of funding our vaccines. So we were quite busy.
Q Yes, but despite that did you in fact take some expert advice on the issue that Dr Wakefield had raised?
A Yes, of course I did, and one of the privileges of working at the Department is the access to people with specific expertise. Whilst there were elements within what he had written that I was able to form my own view on, clearly there were contents within the letter that I did not feel that I had sufficient expertise, and particularly in some of the techniques that were being used for the virology. I am not a virologist.
A I did therefore seek advice from someone who was acknowledged as a measles virus expert.
Q Who was that?
A That was Dr Philip Minor at the National Institute of Biological Standards and Control.
Q Did Dr Minor in his turn suggest that you sought further advice from another individual with a particular expertise?
A Well, you have my correspondence to Philip Minor. Philip Minor replied and his reply was fairly succinct. I phoned him afterwards to try to get a bit more detail, and in the course of that conversation---
MR COONAN: I am sorry, these questions are far too open-ended and my learned friend knows precisely why I am rising to my feet.
THE CHAIRMAN: Ms Smith.
MS SMITH: Well, I do not accept the question was open-ended at all. I asked this witness whether he sought expert advice, he said from Dr Philip Minor and where he worked, and I said to him, “And did he advise you to take advice from somebody else who was an acknowledged expert? Who was that?, so the question was not open-ended, it was in my submission a perfectly appropriate question for examination in-chief, but I am happy, if it assists Mr Coonan at all, to say, “I am not asking you what the advice you were given was, Professor Salisbury”, and I am repeating the same question that I asked before, which is, “Were you in fact advised by Dr Minor to seek advice from somebody else who had an expertise?”
THE CHAIRMAN: Mr Coonan.
MR COONAN: I am more than happy if my learned friend puts it in that way. Indeed, I would go further. The most efficacious way of proceeding might be even to lead the witness on those particular points, and again the learned Legal Assessor, I hope, will understand the basis of my position. Some of these particular matters are clearly uncontentious.
THE CHAIRMAN: Legal Assessor.
THE LEGAL ASSESSOR: Yes, I understand, but maybe Professor Salisbury does not understand the concept of hearsay, and unless parties have agreed that something is evidence from somebody who is not giving evidence, you are not allowed to tell us what they would say. So insofar as you have these questions, if you are asked whether you contacted somebody, you can give the identify of the person but unless there has been agreement, or that person is going to be called to give evidence, you must not tell us what the third party said to you.
THE CHAIRMAN: Ms Smith.
MS SMITH: Well, can I simply repeat the question that I asked before. You have told us that you had advice from Dr Minor, Professor Salisbury, and I asked you whether he advised you to seek advice from somebody else who also had an expertise in the area?
A The answer to your question is “Yes”.
Q Who was that?
A He advised me to contact Professor Bert Rima at Belfast University.
Q Did you understand what Professor Rima’s specialism was?
A He is a virologist particularly with expertise in measles.
Q Then we have Dr Wakefield writing to you again a month after that in December 1992, if you go on to page 15, and that letter is dated 7 December 92:
“Dear Dr Salisbury
Thank you for your letter of 4th November 1992. The paper on measles virus and Crohn's disease will be published in January/February 1993 in the Journal of Medical Virology. I look forward to hearing from you with respect to a meeting between my Group and your Department in the near future.”
So that was a reference back to the previous correspondence between you. Then if we go on, Professor, to page 17, please, this is a letter, later on in the story, in May 1993, and it is addressed to Professor Michael Peckham at the Department of Health. Is he someone who is known to you?
A Yes, of course. Professor Peckham was the Director of Research and Development at the Department.
Q Thank you. We see he says:
“Dear Professor Peckham
Four years ago the Inflammatory Bowel Disease Study Group was formed at the Royal Free Hospital School of Medicine with the specific purpose of looking at the potential role of microvascular inflammation in the pathogenesis of Crohn's disease and ulcerative colitis. Our hypothesis at the time, was that Crohn's disease was mediated by a vasculitis and that this vasculitis was caused by a persistent viral infection of the mesenteric microvascular endothelium. In a series of publications starting with The Lancet in 1989 culminating with the Journal of Medical Virology last month we have not only shown that Crohn's disease is a granulatomous vasculitis, work that has been confirmed by a number of centres, but also that the endothelium in areas of granulatomous vasculitis contains a paramyxovirus. In situ hybridisation and immunohistochemical studies performed by our Group have confirmed this agent is measles virus.
This work has now been duplicated at the University of Connecticut and a Swedish Group headed by Dr Anders Ekbom in Uppsala which have shown that perinatal measles virus infection is associated with an 18-fold increased risk of developing Crohn’s in later life. These observations, from the three independent centres, are compelling and there is an urgent need for further research to confirm these observations.
The most worrying feature of this is that there has been a dramatic rise in the incidence of Crohn's disease in children over the last 20 years: this is a real rise in incidence associated with the same diagnostic criteria and the same physicians making the diagnosis. This rise has been observed to parallel the increase in the uptake of measles vaccination.
We have now reached a critical phase in our studies and further funding is required urgently. Despite this major advance in our understanding of the pathogenesis of Crohn’s disease, the implications of these findings have not been fully appreciated.
Some months ago I wrote to Dr Salisbury of the Department of Health requesting an urgent meeting and he has so far failed to respond in a very positive manner. This is not something that is going to go away and it is going to cause considerable embarrassment if no action is taken at this stage. There is an overriding need for confirmation and I would greatly appreciate a meeting with you at your earliest convenience to discuss the research findings further.”
Did you feel that the criticism that you failed to respond positively was a fair one, Professor Salisbury?
A I did not take it seriously but it was a criticism and so be it. The interval between November and May existed; that was the case.
Q As far as the references to funding, you said Professor Michael Peckham was in charge of research and development. Was that a relevant issue as far as what would apparently appear to be a desire to discuss funding?
A Relevant at one degree, yes, because the research and development division did fund research but the research they funded was essentially policy-based research, not biomedical research, and so work that was being done to look at an association between measles virus and Crohn’s disease, for instance, would naturally have been the territory of the medical research council, so I think one has to understand that whilst the department did fund research through the research and development division, it was specifically policy-related work, not biomedical research.
Q We see the response to that letter which is on page 19 which was copied to you. It came from a gentleman called R B Singh, who was a senior medical officer in the research and development division, is that correct?
A Yes. Professor Peckham would have asked him to take this forward.
Q He said:
“Dear Mr Wakefield,
Many thanks for your letter of 12 May to Professor Peckham on whose behalf I am replying. My apologies for the delay in doing so but you will appreciate the need for internal consultation.
The findings of the study group appear to be as timely as they are critical. However, I think you will agree that many questions remain unresolved, not least that of causation or consequence – a consideration which, as you know, can apply equally to other aetiological agents, some of which have demonstrable intestinal tropism.
Nevertheless, my colleagues and I feel this is an area which merits further exploration. I would be grateful, therefore, if you could let me have an outline proposal which we can consider with a view to discussing your research aims more fully.
It would help if I were to explain briefly how we currently manage research. The department no longer operates a research grant scheme. Although there is a budget for research, it is directed at the needs of ministers and policy makers and is usually proactive in commissioning research rather than responsive to grant applications.
The enclosure explains the criteria determining our research objectives and priorities. In essence, you will first need to satisfy our policy colleagues that the thrust of your research is in keeping with their requirements; hence the suggestion of a meeting in due course.
Thereafter, if your application is acceptable, it will go forward with other contending bids for consideration by the Departmental Research Committee in February of next year. If successful, it will then be submitted for ministerial approval.
If that is granted we will approach you for a formal properly-costed protocol which will go out for peer review.
I hope this is helpful but if you have any queries at this stage please let me know.”
The response to that on page 21 – in a manuscript note we see that it was copied to you – dated 18 June 1993, says:
“Dear Dr Singh
Thank you for your reply to my letter regarding the role of measles virus in Crohn’s disease. I concur entirely with your point with respect to agents which exhibit tropisms for the intestines.
I am presently preparing an outline of our research programme which I will send to you in the near future.
Thank you for your interest.”
Were you aware of any submitted proposal after that letter, Professor Salisbury?
A No, I do not believe the department ever received any such outline or any such proposal.
Q The next letter is to you from Dr Wakefield and it is at page 47. It is dated 4 October 1994:
“Dear Dr Salisbury
You will remember that I wrote to you last year regarding the work of my group on the potential role of measles virus in the aetiology of Crohn’s disease.”
He quotes the reference in the Journal of Medical Virology in which that was published.
“When I wrote to you I requested a meeting to discuss further the potential implications of the rising incidence of Crohn’s disease in children and the uptake of the measles vaccine. To my surprise and disappointment your interest in the data was limited and therefore we have not had an opportunity to meet. We have recently concluded a two-year programme of research designed to confirm the persistence of measles virus in the gut by the technique of immunogold electron microscopy. This work was presented recently to the British Society of Gastroenterology. This study made no claims of an aetiological role for measles virus in Crohn’s disease; rather it sought to confirm persistence of measles virus infection in intestinal tissues and this it did. In addition we have recently completed a prospective study evaluating 4,000 individuals given live attenuated measles vaccine in 1968 followed by the Medical Research Council and compared them with 10,000 age and sex matched controls who were not vaccinated. I am not in a position to reveal the results of these data to you for the moment; nevertheless, they give cause for concern.
I am well aware of the value of measles vaccination and indeed my own children have been vaccinated. However, you are currently conducting a programme of re-vaccination of children who were vaccinated in early life. You will doubtless have seen a paper by Dr Ekbom in The Lancet entitled Perinatal Measles Infection and Subsequent Crohn’s Disease which underlines my worry about the age of exposure to measles virus (or vaccine). I am even more concerned that re-challenge with the same antigen later in life will lead to the onset of Crohn’s disease. Although it is too early to have data on this, I fear we face a potential catastrophe in the form of an epidemic of Crohn’s disease.
I do not believe the government can continue to ignore our work any longer and the time has come to resource this work appropriately in order that we can either establish or refute a link to everyone’s satisfaction. I urge you to consider a proposal to meet and discuss this and I look forward to hearing from you at your earliest convenience.”
Dr Wakefield sent a copy of that letter to Virginia Bottomley, who was then the Minister of Health, and to the Chief Medical Officer, Dr Calman. You responded to that in two letters, if I may take you on to those, one at page 49, dated 21 October:
“Dear Mr Wakefield
Your letter of 4 October has been received by Mrs Bottomley and I have been asked to reply.
I believe that you have already spoken to Dr Calman, the Chief Medical Officer, and steps are being taken to arrange a meeting in the near future.”
There is another one of 25 October:
“Thank you for your letter of 4 October. Unfortunately this did not arrive at my office until Monday 17 October, perhaps because it was sent to my old address.
As I believe you now know, we are trying to arrange a meeting to discuss the issues of Crohn’s disease and infectious agents …”
It would appear from that, Professor Salisbury, that there had been some communication that you were aware of between Dr Calman and Dr Wakefield direct, is that correct?
A I presume so, yes, otherwise I would not have made that comment.
Q As a result of this correspondence was a meeting convened at the Department of Health?
A Yes, indeed it was.
Q Turning to page 57, we can see the chairman’s briefing on that meeting which sets out the purpose of it:
“Correspondence from Dr Wakefield at the Royal Free Hospital has made the CMO aware of new evidence linking measles virus infection and Crohn’s disease.”
It says that there was a different theory by Professor Hermon-Taylor at St George’s Hospital about the infective cause of Crohn’s disease, is that correct?
A Yes, that is correct.
“It was agreed that a meeting should be held as soon as possible to allow these doctors to present their research findings before an audience of invited experts.”
It refers to the fact that the other doctor involved had been unwell.
“Dr Wakefield’s evidence suggests an association between measles immunisation in the second year of life and subsequent Crohn’s disease. This is bound to be considered in relation to the recent national immunisation campaign among children 5-16 years. Knowing of the new work, it was judged that the national campaign was still needed; it might save up to 50 deaths. Furthermore, Dr Wakefield suggested that if immunisation really has unwanted effects, the danger period may largely be restricted to the first years of life when children mount an imperfect immune response. Evidence from the United States where there is a two dose immunisation regime does not suggest an increased incidence of Crohn’s disease.
The objective of the meeting is to give a fair hearing to the latest evidence on the aetiology of Crohn’s disease and to consider what steps (if any) should be taken by the department in future. One possible step is to commission, or cause to be commissioned, further necessary research.”
Was that your understanding of the reason that the meeting was being convened?
A Yes, it was.
Q If we turn to page 51, we have the actual minutes of the meeting. We see the attendees at that meeting from the Department of Health were Dr Metters chairing it, is that correct?
A Yes, he was the Deputy Chief Medical Officer.
Q You were one of the attendees from the Department of Health.
Q Externally we can see Dr Philip Minor to whom you have referred, Mr Wakefield himself, Professor Zuckerman and Professor Hodgson from the Royal Free Hospital. Others may wish to take you to the entire meeting, Professor, but I am simply going to the summing-up which is on page 56. We see there:
“Dr Metters (chair) suggested two separate areas to be tackled – basic scientific questions under discussion and possible media response to the debate about the safety of measles immunisation.
Researchers round the table considered that insufficient funds are made available for the investigation of inflammatory bowel disease. Dr Metters indicated that within the research and development department they would consider what action might be possible and which other organisations, including the Medical Research Council, might become involved.”
It then sets out the detail of what could be done in that area.
“Discussing possible media response to the debate about measles immunisation, Dr Metters expressed gratitude to Mr Wakefield for alerting the department in advance of publication. Dr Metters suggested that PHLS should communicate any possible criticisms directly to Mr Wakefield and that Dr Salisbury should maintain links between Mr Wakefield and the department.
To consider the case for a wide-ranging review of the current research literature in this area and to consider the need for Medical Research Council involvement.
To maintain links between the department, the Inflammatory Bowel Disease Research Unit, the Royal Free Hospital of Medicine and the PHLS Communicable Disease Surveillance Centre.”
Turning back to paragraph 17 on page 54, because this becomes relevant to subsequent correspondence:
“Professor Zuckerman reported that the Royal Free Hospital School of Medicine anticipates intense media interest in this study and plan to hold a press briefing. This will include a printed information pack to help prevent misunderstandings and unnecessary public alarm. The briefing will take place when results are first published, problem in February or March 1995.”
I emphasise for the Panel’s point of view 1995 – we are on the earlier publication, not The Lancet paper with which we have been concerned.
“Professor Zuckerman suggested that it might be helpful for the Department of Health and the Public Health Laboratory Service to be involved in preparing the press briefing. Dr Metters expressed gratitude to Professor Zuckerman for this offer and suggested that Dr Salisbury would be the appropriate departmental contact.”
Reverting to the conclusions and the action points on page 56, Professor Salisbury, were you taking the whole issue of Crohn’s aetiology seriously by holding this meeting?
A Yes. The very fact that we had done this, that we have brought at least two competing views of different infectious aetiologies attests that, yes, this was being taken seriously.
Q As far as the action points – to consider the case for a wide-ranging review of current research literature – might that have been something that would be considered for funding by the research development department of the Department of Health?
A I do not know whether they were actually thinking that they would look at the current research or that they would commission someone else to do that, I do not know.
Q Dr Wakefield wrote to Dr Metters, the chair of that meeting, and we can see his letter at page 58:
“Dear Dr Metters
Thank you very much for the meeting on 10 January 1995 at which we were able to present some of our data on the aetiology of Crohn’s disease. Despite the fact that the meeting did not, to my mind, provide a clear way forward, please feel free to call on my services at any time to provide information about inflammatory bowel disease in general, or our work in particular.”
You responded to that letter at page 59 on 3 March 1995:
“Dear Mr Wakefield,
Thank you for your letter of 2 February.
You point out that it was sent to the wrong address.
I have discussed your comments with colleagues from the department who attended the meeting in January.
The meeting that we held was arranged for the department to hear at first hand from two different groups who had work in progress on the aetiology of Crohn’s disease. This briefing meeting was not intended to decide Department of Health policy. We do wish to hear directly from researchers but there was no question of that meeting deciding departmental policy, nor giving commitments to supporting particular work.
The department, in its public health role, has to consider the effects of research results that may call in question established policies, such as routine childhood immunisation, and this makes it all the more important that any results that call this into question have to be rigorously tested in the scientific arena.
The department’s role is not to endorse, interpret or reject findings, but to make sure that there is proper debate about the significance of these findings in scientific and medical circles and that the public are not inappropriately alarmed by the results. To this end, once the findings are fully in the public domain we may well be able to commission a detailed review from independent experts.
I am sorry if you were disappointed that the meeting appeared not to support the taking forward of your work. Nevertheless, we remain most interested in the progress of your studies and hope that you will keep us informed.”
Did that letter reflect the standard view that you would give, Professor Salisbury, to an individual researcher who had approached you in this way?
A I am not sure what you mean by “approached in this way” because we were already in fairly unusual circumstances.
Q Perhaps I should have asked you about that. You say it was unusual; was it unusual for a doctor with a particular research interest that might impact in some way on the Department of Health policy in relation to anything to write to the Department of Health about that research?
A Doctors do obviously write to the Department and not just doctors; the public also write with particular opinions that they may have. This was an unusual sequence of events where we had gone through requests for funding and Dr Singh had explained, I think fairly quickly, what the process of departmental funding was. We had not ever received an application as requested from Dr Wakefield yet he was still insisting on the need for us to fund his work. The word had not had the sort of scrutiny that we felt it would require if there were to be any sort of policy implications that came from it and, whilst I clearly am inhibited from giving any hearsay information, we also had sought other people’s views.
Q You have said that the department’s role was to make sure that there was proper debate about the significance of any findings. Did you feel that the meeting that had been held had to some degree assisted with that role?
A That was the purpose of having other individuals who had specific expertise present at that meeting. This was not a meeting just of departmental officials, Professor Hermon-Taylor and Dr Wakefield. There were individuals who had expertise in inflammatory bowel disease, in measles virology and in epidemiology.
Q You said in that letter,
“… proper debate about the significance of these findings in scientific and medical circles, and that the public are not inappropriately alarmed by the results.”
In this context, to what were you referring when you talk about a concern for public alarm?
A If you go back to the minutes of the meeting, you will see that some of the area of discussion was around the epidemiological data where two different cohorts of individuals were being compared to look to see if there was an increased risk of inflammatory bowel disease in a vaccinated cohort and, if this was given a degree of promotion that it implied a risk of inflammatory bowel disease from measles vaccine, we felt that needed to be handled very carefully.
Q The ultimate paper on the subject of “Is measles vaccination a risk factor for inflammatory bowel disease?” was sent to you prior to publication with a letter from Dr Wakefield. At page 61is a handwritten letter from him and, doing my best because it is both handwritten and a little faded, I think it says,
“Dear Dr Salisbury,
Our paper entitled ‘Is measles vaccination a risk factor for inflammatory bowel disease?” is due to appear in The Lancet on 28 April 1995. I enclose a copy of The Lancet proof for your attention. Please would you let me know if the department intends to set up a ‘helpline’ and if so what the number will be. We can then communicate this to patients and relatives through the appropriate sources.
As far as the suggestion of a helpline was concerned, Professor Salisbury, you responded. We see the paper is attached at pages 62 to 68 and then there is a response from you on page 69 dated 20 April 1995,
“Dear Dr Wakefield,
Thank you for kindly sending me the proof of your Lancet article.
The Department of Health has standing arrangements for the provision of public information and these will be available for the public should this prove necessary after the publication of your article. If we find that we have to activate our helpline, I will advise you of the arrangements at the time.”
Did the suggestion by Dr Wakefield that you might need a helpline cause you any concern?
A This was really unusual. Yes, we were somewhat concerned. We really had not actually come across the circumstances the same as this when forthcoming publication of a piece of work was being viewed in such a light that we would need to set up a helpline. The department does have a public inquiry office that takes calls from the public and, if necessary, briefing is provided to the public inquiry office in order that they are able to answer specific questions when the public phone and, under circumstances that I can remember, that has either sufficed or alternatively calls are put through directly, for instance on immunisation matters, to my team and we deal with them. Clearly, there was considerable ebb and flow and sometimes the pressure of those phone calls is intense, particularly in regard to the issue that we are here today about, but none of us have experience of the department setting up a helpline and we wondered why anybody would need to do that unless this was being put into the public domain as some very important observation of a great risk.
Q I think that in fact the department issued a press release and, if you go to page 70, you will see that press release.
“Press Statement on Crohn’s Disease and Measles
‘The Department of Health is aware of the research currently reported by the team form the Royal Free Hospital. Although the Royal Free Hospital work suggests a possible link associating measles vaccine as a factor to explain the rise in Crohn’s disease, many causes such as other infections, genetic markers and auto-immunity have been implicated by other researchers. Indeed, Crohn’s disease was well known long before measles vaccine was developed and the UK rise in Crohn’s disease predates the introduction of measles vaccine. Independent work from Japan, using the most up-to-date methods of genetic fingerprinting has failed to support the Royal Free findings.
The Department of Health has already held a meeting of experts to listen to the Royal Free Hospital and other work on infections that may play a part in Crohn’s disease. The Department will/is commissioning a detailed report from independent experts that will investigate this and other theories about infectious disease being causally linked to Crohn’s disease.’”
Is the reference to the meeting of experts there and the possibility of commissioning detailed work a reference to the meeting that took place with the group from the Royal Free that we have just looked at?
A Yes, it is.
Q You have told us that it was quite unusual for a researcher to be writing to you about helplines and that that caused some concern. Did that concern play any part in the decision to release a press release about this matter?
A Clearly, we were very concerned that the way in which this was being put to us, public concern was indeed going to be engendered one way or another. It was important, not least of all for health professionals who would be dealing with parents and patients, to be able to have at least something to turn to. Doctors do not enjoy finding out information from their patients that they would prefer that they had at least been alerted to earlier in order that they can answer their patients’ questions.
Q You have told us that you had consulted various independent experts in relation to this matter and you have referred already to Dr Minor and to Professor Rima. I think it is right that, at that stage, you also went to Dr Stephenson who specialises in measles virus at the London School of Hygiene.
A He did at that time, yes.
Q Thereafter, I want to take you on to the next correspondence from Dr Wakefield which was in September 1996 and is at page 193. This is a letter from Dr Wakefield directly to Dr Calman, the Chief Medical Officer, and there is a manuscript note at the top indicating that it was handed on to you. I do not propose to read again the whole of it and others may wish to take you to other parts, professor, but may we run through it.
“Dear Dr Calman,
I am writing to you in order to express formally my anxieties over your intention to re-vaccinate all pre-school children prior to school entry. I will not go over the history of our exchanges on this subject; this will emerge at the appropriate time.
I feel sure that your independent expert advisers will have alerted you to the detection of vaccine-strain measles virus in children with autoimmune hepatitis, a disease in which measles has been implicated previously on evidence far, far more tenuous than our own for measles and Crohn’s disease.
Doubtless they have also informed you …”
and he then goes into the characteristics of the measles vaccine that he suggests are relevant.
“Persistent infection following vaccination is, therefore, not only biologically plausible but likely.
You will also have seen our recent paper in the Lancet which provides what many consider to be compelling evidence of a causal association between measles and Crohn’s disease following exposure in utero. No doubt your experts will be able to reassure you on this particular issue.
In the future you may have cause to reflect on the ‘independence’ of your appointed experts. Certainly, Dr Miller from the PHLS and Professor Minor of NIBSC cannot be considered independent. If I and my colleagues are right, then they are wrong. Their scientific and professional standing and credibility is inextricably linked to the success of measles vaccination. You may also wish to consider the value of their advice with respect to the depth of their knowledge about measles virus. I refer specifically to comments made by Dr Miler and yourself in letters to the Lancet following the ’94 revaccination campaign (following which paediatric IBD cases have increased dramatically).
In your letters you quote from a letter to the Lancet provided by Professor Herman-Taylor …”
and we have heard his name of course in relation to his theory about Crohn’s Disease.
“Hermon-Taylor illustrates that the emergence of Crohn’s disease in the 1940-50s in the UK took place before either the disappearance of measles epidemics, or the introduction of measles vaccination. Hermon-Taylor puts this forward as categorical evidence that neither measles nor measles vaccine can possibly be the cause of Crohn’s disease, which you and your experts endorse. This is a superficial and naïve perspective that reflects a profound lack of understanding of either the changing pattern of morbidity and mortality from measles in the UK leading up to the emergence of IBD, or the risk factors for persistent infection and delayed disease that are associated with measles virus infection.”
He then sets out his arguments in relation to the rising incidence of Crohn’s disease in three UK centres plotted against measles notifications in England and Wales with graphs indicating that or purporting to do so and he then says,
“It is my concern that the expert advice that you have received has been deficient, and far from independent. If and when the dam bursts it will be you and your department that is standing in the way. We, for our part, have tried to help, only to have our work denigrated and misrepresented. We went into this with our eyes open and will continue to generate peer-reviewed, published data in the true scientific spirit: there is a vast gulf between this and opinion. You may wish to ask your experts what are the longest prospective safety trials of measles vaccine, MMR, and measles re-vaccination at any time, anywhere in the world. The result may surprise you.
Do not re-vaccinate.”
That was the letter that was sent to the Chief Medical Officer in September 1996 relating to this whole issue of the implication of Crohn’s disease in measles vaccination and in fact, copying you in, Sir Kenneth Calman replied to that letter himself and his reply is at page 238.
“Dear Mr Wakefield,
Thank you for your letter of 7 September bringing to my attention your concerns about measles immunisation and inflammatory bowel disease.
The recent recommendation from the Department of Health, for a routine second dose of measles/mumps/rubella (MMR) vaccine, followed careful deliberation by the Joint Committee on Vaccination and Immunisation (JCVI), on the most effective national policy for the control of measles, mumps and rubella. The JCVI is an independent expert advisory group with wide representation, whose remit is to advise the Secretaries of State on vaccines and diseases potentially preventable through immunisation. Before coming to its final decision, the Committee has been provided with your published material, as well as that published by other researchers in this field. The JCVI was of the view that the arguments in favour of a second dose of MMR vaccine outweighed those against it. I will ensure that the JCVI is alerted to your continuing concerns, as expressed in your correspondence.
I am sure that you are aware that the present UK strategy of the achievement of high coverage with the first dose of MMR, a campaign to interrupt transmission and reduce susceptibility, followed by a routine second dose, is fully in accordance with [World Health Organisation] policy for industrialised countries.”
You did not write that letter, Professor Salisbury; it came from the Chief Medical Officer but you were copied in to it. Did it reflect your views as well?
A Yes. I certainly contributed to the drafting of it.
Q Subsequently to that in February 1997, a JCVI group of experts attended a presentation by Dr Wakefield at the Royal Free Hospital and you are aware that we have heard evidence from other witnesses in this case and in fact we have heard about that meeting already from Professor Sir David Hull who attended it. Did you also attend that meeting?
A Yes, I did.
Q I think it is right – and again I do not need to go into the contents but the result is important – that a report was written after that meeting and that again the JCVI continued to recommend the MMR programme and the Department of Health continued to implement it.
A Yes and I think it is important to say that the report that was written for the JCVI was actually written by Sir David Hull. It was not written by us from the department.
Q The next batch of correspondence with Dr Wakefield in fact was with you and was on a separate though related subject with regard to comments he alleged that you had made about his work. Would you turn on, please, to FTP2, the next volume, and to page 395. This is a letter that was written directly to you from Dr Wakefield and, if we turn to page 396, we will see that copies of the letter were sent to the Medical Protection Society, which is one of the doctor’s defence unions, but also to Dawbarns Solicitors; is that correct?
A That is correct.
Q If we look at the letter it reads:
“Dear Dr Salisbury,
Please could you confirm that during a discussion on 18 February 1997 with the mother of one of our patients …”
And this is a patient who was referred to in The Lancet article and whose number is one:
“… [child one] you stated the following:
1. That internationally, there was o support for our work.
2. That the research published by our group was of a poor standard, and
3. That histological analysis of the tissues from her son’s colon, if analysed elsewhere, would be unlikely to show inflammation.
Further, please could you confirm that in an interview with Mrs Jennifer Nagel, Home Affairs Editor, ITN News you stated that:
1. No-one has been able to confirm our work worldwide, and
2. That we have been ‘laughed out of court’.
If this is not what you said then I would be grateful if you could state what you did say in the precise form of words.
I look forward to hearing from you at your earliest convenience.”
I think rather than asking you whether that is correct, I can take you on to your response which is at page 408, dated 27 March 1997, and reads:
“Dear Dr Wakefield,
Thank you for your letter of 12 March.
During a lengthy telephone conversation with [Mrs 1] … witnessed by a colleague, I pointed out that other international research had so far been unable to confirm your work. I also referred her to the editorial in The Lancet of 29 April 1995 and subsequent exchanges in the correspondence columns.
Where the histological analysis was concerned, I commented that it would be interesting if the tissues were exchanged by a group who did not share your convictions.
In an interview with Jennifer Nadel, Home Affairs Editor, ITN on 23 January 1997, witnessed by two Departmental officers, I said that your research was interesting but had not been replicated.
At no stage in either conversation did I say that no-one had been able to confirm your work worldwide or that you have been ‘laughed out of court’.”
Did that letter accurately represent what you had said in relation to the allegations that had been made by Dr Wakefield?
A My reply or Dr Wakefield’s letter?
Q Your reply.
A Yes, it did. We used to take quite lengthy telephone calls from this particular person, who would phone quite distressed and would want to talk for a long time, and it happened that on this particular occasion a colleague who had the office next door to mine was actually with me at the time that the call came through and sat throughout the call. In the circumstances of the second issue, that with Jennifer Nadel, there were two departmental press officers present at the time and therefore they were able to answer. I think this is probably the first time that we actually got advice from our solicitors about dealing with Dr Wakefield. Of course there were many occasions after that when we had to.
Q As far as the first conversation where you said you were rung up by the distressed individual, you mean the lady I have calling “Mrs 1” do you?
A Yes, I clearly know her by a different name.
Q Of course. As far as the interview with the Home Affairs editor at ITN was concerned, that suggests there was some media interest by that time, is that correct?
A Yes, she had come to the department to have this discussion.
Q About Dr Wakefield’s research in particular?
A Yes, very much so.
Q The next thing that we have is a letter, into which you were copied, from Dr Wakefield to a member of parliament, and that was in July 1997, so three or four months later, and it is at page 494. This is a member of parliament called Llew Smith, and it is a letter from Dr Wakefield, and we see at the bottom “Copy: Dr Salisbury”. It says:
“I understand that you raised the issue of measles/MMR vaccines with Tessa Jowell yesterday. We have a considerable body of new data, in addition to the data already published in peer-reviewed journals which, contrary to the line being fed to the Minister, does stand up to scientific scrutiny, and has now been reproduced elsewhere in the world.
I would be happy to meet with the Minister, and discuss this data. It would be helpful for Richard Barr and Kirsten Limb to be present since they have amassed a most comprehensive data-base on this subject. However, I am not prepared to waste any further effort in presenting these data to Dr David Salisbury. I also wish to make it clear to the Minister that the JCVI may be independent of the Government, but is far from being independent on the subject of vaccination and vaccine safety.
You have alluded to the Government’s response to Gulf War Syndrome. It is extraordinary that both the Government and the MoD have acknowledged the existence of such a syndrome and have been prepared to recognise the likely vaccine link, based upon evidence far, far more tenuous than that put forward for measles virus, measles vaccine and Crohn’s disease. The simple truth is that if we and others are right, then the consequences are too drastic even to contemplate – that is unless you are faced with dealing on a daily basis with the children whose lives have been destroyed by this disease.”
Just to make it clear as we go along, professor, this is still referring to the risk of Crohn’s disease simplicita being caused by vaccination, is that correct?
A Yes, that is certainly my interpretation of this. I have to point out that the route of this letter coming to me was that it actually was sent also to the minister, the Minister of State Tessa Jowell, and so she sent it on to us. She clearly thought it was important that we had sight of it. My interpretation of this was that it related entirely to measles vaccine and Crohn’s disease and consequences that were too drastic even to contemplate.
That was in 1997. The letter that Sir Kenneth Calman had sent in response to the letter to him, to which I referred you previously, did that still sum up the view of the Department of Health on this particular issue of whether measles vaccine played a role in Crohn’s disease?
A Yes, I have – I presume you are talking about the September 1996 letter?
A This was a very strange letter. It was strange scientifically; it made claims for entirely new biological phenomena, that measles vaccine was persisting, which there had never been evidence of hitherto; it attacked individuals by name; it threw together data that was not necessarily meaningful and put together in the way that it was, and it implicated measles vaccine in a condition called sub-acute sclerosing panencephalitis, and this was an attempt to try to show that measles virus from the vaccine could persist and there has never been evidence of measles vaccine in SSPE and the introduction of measles vaccination eliminated SSPE. This was a very odd suggestion of an entirely new biological phenomenon and the zeal that Dr Wakefield expressed for us not to revaccinate children was not supported by any evidence of harm that might come to those children, but if we had followed this we would have left children at risk of harm, and this was why the chief medical officer answered in the way that he did, that our policy was not influenced and it was based on the advice that we had got from the Joint Committee on Vaccination and Immunisation.
Q That relates, as we have established, to the risks in relation to Crohn’s disease. Did there come a time when Dr Wakefield’s apparent concerns about the risks associated with vaccination extended into other areas of possible ill health?
A Yes, the evidence for links between inflammatory bowel disease and measles vaccination rather evaporated. There was epidemiological evidence that measles vaccination was not a risk factor for Crohn’s disease; there was virological evidence that you could not find measles virus, and, indeed, I believe Dr Wakefield himself published that he could not find measles virus in Crohn’s disease, and the story moved on and I believe it is in the summary of 1997, we then were contacted by Pulse, I was actually on holiday at the time but the department was contacted by a medical newspaper called Pulse to ask us about reported associations that were being found at the Royal Free between inflammatory bowel disease and autism.
Q Was that the first mention of autism as far as the department was concerned in this context?
A It was certainly the first public recognition. I suspect we probably knew that work was already going on involving children with autism but the first public acknowledgement was this contact from Pulse.
MS SMITH: Sir, I am now going on to the issues relating to the correspondence in relation to the autism vaccination link, so it is a marginally different subject. Would you care to break now for a short time?
THE CHAIRMAN: Yes, but because we are rising early we will take a fifteen minute break.
Professor Salisbury, you are still under oath so please do not discuss your evidence with anybody during the break.
THE CHAIRMAN: Ms Smith?
MS SMITH: Thank you. (To the witness) Before the adjournment, professor, you had just told us that there came a time when you became aware, at least officially, that Dr Wakefield’s concerns with regard to vaccination were extending into the area of autism. You said that you first became aware of that because of an article in Pulse. Can you tell us, although we have heard about this Pulse article before I am not sure we have ever made it clear to the Panel, is Pulse a sort of – I am not sure how to describe it – a sort of newsy medical journal as opposed to a serious one?
A I have to be very careful what I say. It is a weekly medical newspaper.
Q So it is about news issues and gossip rather than being a scientific journal full of peer review papers is it?
A It is not the latter.
Q If we look at page 501, this is a printout, Professor Salisbury, and we see that it says:
“Pressure on the government to order a full review of alleged links between MMR immunisation and a range of serious illnesses grew this week with the emergence of fresh research evidence.
The Department of Health has so far rejected suggestions of a link between MMR and MR vaccines and a rising incidence of Crohn’s disease and autism in children.”
If we go to the bottom of the page:
“Dr Andrew Wakefield, reader in medicine at the Royal Free Hospital, London, and one of the authors of the five new papers, first published research on the topic in The Lancet two years ago.
At the time, his findings were dismissed by department officials as flawed. Dr Wakefield told Pulse: ‘The (new) papers are the results of collaboration between other countries and centres in the UK. They build on the work already done. The results clearly confirm our suspicions and take them further’, he said.
‘We have not enough published evidence to change policy at the moment but we have accumulated enough evidence for Tessa Jowell to conduct an independent review. It could lead to a profound rethink of vaccination policy’.”
And then going down to the details of that:
“New evidence for a link between MMR immunisation and Crohn’s disease and autism is contained in five, as yet unpublished studies examining different aspects of the topic.
Dr Andrew Wakefield, reader in medicine at the Royal Free Hospital in London, said the studies were designed to enable evidence to be looked at from several angles – ‘a bit like fitting together the pieces of a jigsaw’.
He said no one paper on its own was enough to be persuasive. ‘We have therefore looked at every aspect to see if the findings support earlier work. The papers awaiting publication include epidemiological, cohort and case-controlled studies’.”
Then he told Pulse about Crohn’s disease and ulcerative colitis and he says:
“We have also identified the measles virus in Crohn’s disease tissue, he said. Dr Wakefield also told Pulse he was currently receiving around five to six referrals by GPs each week of children with Crohn’s or autistic disturbance believed to be precipitated by MMR vaccine.
He said criticism of his previous findings by the Chief Medical Officer … and other government officials showed a lack of understanding.
The criticisms focused on the alleged ‘epidemiological weakness and lack of biological plausibility’ of the studies – allegations which Dr Wakefield strongly denies.
He said the new studies addressed the criticisms which he did not believe to be valid in the first place.
He argued that until safety concerns were allayed, polyvalent MMR and MR vaccines should be separated and given individually.
‘The Department of Health’s ‘watching brief’ policy is unacceptable’, he said.”
Then there are various quotes from letters relating to the subject.
Were you aware of the reaction of the press generally to that article coming out in Pulse?
A When that article came out, as I have said, I believe I was on leave at that time, but, clearly, there were an awful lot of press cuttings that I saw on my return.
Q Did Pulse actually themselves contact the Department of Health in relation to the issue?
A I think they must have done because if you look at the timing of the letters and the article, you see that, I believe, Sir Kenneth Calman wrote to the Royal Free to try to get some more information, and his letter – I am doing this from memory – is dated late July and the by-line for this article is 2 August, so I believe that Pulse must have contacted the department and asked for a comment sufficient that Professor Calman then contacted the Royal Free.
Q You are quite right because if you look back to page 497, that is a letter dated 29 July 1997, from Sir Kenneth Calman to Dr Wakefield:
“I understand from the media that you have new evidence for a link between MMR immunisation and Crohn’s disease and autism, which will be published within the next six months. The Department is getting several enquiries from the media about this, and it would be helpful if you will let me have a copy of the research evidence to which you refer, or an outline of the projects.”
So it certainly looks as though he became aware of it before the actual publication in Pulse.
The response to that letter was in fact by Professor Pounder, Dr Wakefield being on annual leave, and we have got that at page 498. It is dated 30 July:
“Mr Andrew Wakefield is on annual leave this week, hence I am replying to your fax of 29 July 1997.
The media attention caught us by surprise, and we would have much preferred that it had not taken place. Mr Wakefield had responded to a routine, apparently informal telephone call from Pulse, not realising that the conversation would be published. The information concerning our planned meeting was given to Pulse by Mr Llew Smith MP. I spent yesterday trying to lower the temperature, fully realising that you and JCVI have yet to receive the results of our latest studies.
Raising our concerns that there may be a link between MMR vaccination and atypical forms of autism and inflammatory bowel disease, the latest data are:”,
and then he says firstly:
“A detailed clinical and pathological examination of children with the alleged syndrome, that not only shows that the majority of these children do have histologically confirmed intestinal inflammation, but also they ….. have a persisting infection with measles virus, as identified by immunohistochemistry. These initial studies are nearing completion, and we would expect to complete this work in a matter of weeks.”
“An epidemiological study involving one of the birth cohorts, that shows that the occurrence of wild measles infection and mumps infection within the same year of life increased the odds ratio 12-fold for the likelihood of developing inflammatory bowel disease in the first 25 years of life, compared with controls. This study is nearing completion.
Japanese workers have ….. been able to identify measles virus genome by PCR when investigating coded samples supplied by us from patients with both inflammatory bowel disease and also from children with alleged MMR autism/inflammatory bowel disease.
Workers in the United States have confirmed an association [by] wild measles infection in early life and the later development of inflammatory bowel disease.
We will certainly keep you informed of developments. However, I must say that our confidence was not encouraged by what happened when we published the paper in The Lancet a couple of years ago. We provided you with the full information in advance, and the Medical School and Trust tried to present the information in a calm and careful manner. We did not appreciate your pre-publication ‘strike’ against our work at your press conference on the Wednesday. We would greatly appreciate an understanding that we will try to work-out this problem together, rather than pouring scorn on the other side.
I am in London for the next six weeks so, if an informal conversation would be helpful, I would be ….. happy to meet you.”
As far as that letter is concerned, Professor, I will go on to the response, which is a very brief one, from Sir Kenneth Calman, but, firstly, do you know what was meant by the suggestion that there had been some sort of pre-publication strike in relation to a previous paper by the Royal Free?
A Well, this is the press statement that you read out that we had issued coincident with the paper on measles vaccine and risks of Crohn's disease, because we felt that it was important to try to get a balance out simultaneously rather than having to try to chase after a genie that was going to be very difficult to put back into the bottle.
Q Now, you have already told us that that press release was issued after a letter from Dr Wakefield asking you whether you were going to have helplines set up. Were you concerned with pre-publication strikes against the work, or what were you concerned with when you wrote that press release? What was your concern?
A Were we concerned with pre-publication strikes? I mean, we were accused of a pre-publication strike. We felt it was important to try to get at least our view simultaneously into the public domain as the measles vaccine/Crohn's disease article was published. I think what is being said here is that they would appreciate it if we did not do that.
Q Yes, but what was your purpose for wanting to get something, as you say, into the public domain?
A To try to make sure that there was at least a balance between the claims that were being made and the view that we held that this was not necessarily as clear cut as had been presented.
Q What did you see the consequence of not having a clear balance presented to the public as being?
A Well, the story would have a credibility that perhaps was greater than was justified.
Q As far as you were concerned, we have been through the previous history, but were you pouring scorn on the work that was being done at the Royal Free?
A Our press statement is our press statement. I do not believe that that was pouring scorn on the Royal Free.
Q There was a response to that letter and that is on page 500, and that was to Professor Pounder simply saying:
“Thank you for your letter ….. in response to mine ….. to Mr Wakefield.”
A I am sorry, my page 500 is Sir Kenneth Calman to Professor Pounder.
Q Yes, that is exactly right, a response to the letter from Professor Pounder.
Q “Thank you for your letter, received today, in response to mine of yesterday to Mr Wakefield.
I look forward to receiving the results of the latest studies set out in your letter; perhaps we can consider the need for informal discussion following this.”
Did subsequently the envisaged meeting, chaired by the Minister For Health at that time Tessa Jowell, in fact take place?
A Yes, it did.
Q If we go on to a letter from in fact Professor Walker-Smith on page 617, we see a reference to that meeting. This is a letter from Professor Walker-Smith to Sir Kenneth Calman dated 14 October 1997:
“Dear Sir Kenneth
I enjoyed meeting you at the very successful meeting chaired by Miss Tessa Jowell ….. Minister for Health. I am very glad that you made the proposal to have a CMO seminar on this contentious topic as I really [feel] ….. this is the only way forward.”
He then raises an issue, which you can be taken to by others if they wish to do so, in relation to some epidemiological figures relating to Crohn's disease that you had raised with him at that meeting, is that correct?
A Yes, that is correct. At the end of the meeting, during which we had heard again about these huge increases in inflammatory bowel disease, particularly Crohn's disease, in children, and that this was linked with measles vaccination, and also there was the reimmunisation threat that we had been exposed to, we actually had data that showed that actually since the measles/rubella campaign of 1994 there had been no increase through extensive surveillance of inflammatory bowel disease across the relevant cohorts.
Q You wrote back in fact, although the letter was addressed to Sir Kenneth Calman, you responded to it on 21 October, if we go on to page 621.
A Well, I think if you look on page 620, John Walker-Smith actually wrote to me as well.
Q Thank you. You are quite right. Perhaps I should go to that first.
I felt it was a very valuable meeting we had at Richmond House yesterday and I was pleased that Sir Kenneth Calman has agreed to arrange a chief medical officer seminar in due course on the issues related to autism, bowel inflammation and the possible role of MMR.”
Then he makes the same point:
“You did however rather surprise me at the end of the meeting when you briefly flashed in front of me the figures concerning hospital admission for Crohn's disease”.
He makes an inquiry as to what those figures were based on. He says:
“On the issue of autism, I am completely astounded by the clinical features of these children with autism and bowel inflammation. Very often the gastrointestinal symptoms have been ignored by a succession of doctors and the findings on ileo-colonoscopy appear to be quite distinctive. This seems to be a whole new syndrome which is in urgent need of clarification.
I look forward to seeing you at the [Chief Medical Officer’s] seminar”.
Then you wrote back to him on 21 October, which is the next letter, and you thank him for his letter and you tell him that the data that you had available for the meeting were the hospital episode statistics for 92-96 in relation to hospital discharge. You deal with the details of that epidemiological evidence, and you say:
“the epidemiological case for any association between IBD and measles containing vaccine looks very shaky indeed.
Turning to the issue of autism and Crohn's disease, I would ask you to wonder why other gastroenterologists have never noticed that amongst their IBD populations they were not struck by the number of young people who were autistic. This is such an unusual association that it must have been noticed by other gastroenterologists if it were in any way meaningful. You might also like to wonder how it has failed to be observed in the United States where over 150 million doses of MMR vaccine have been used, should there be any causal association with vaccine.”
You say you would be delighted to discuss those issues with Professor Walker-Smith. Then if we go on to 623 we see Sir Kenneth Calman’s brief reply on the same issue relating to the figures that you had produced. Now, at that meeting with Miss Tessa Jowell, was there indeed an intention expressed to have some sort of CMO seminar, some sort of scientific meeting to discuss the issue again?
A Yes, that was undoubtedly the conclusion of the meeting, that the CMO felt that he needed to be able to hear as much of the available evidence involving measles, measles vaccine, inflammatory bowel disease, autism as he possibly could.
Q There is a little tranche of correspondence relating to that meeting, and it starts on page 625, and it is from Dr Wakefield to Sir Kenneth Calman, again copied to you at the top of the page:
“Dear Sir Kenneth
Further to our discussion regarding the proposed meeting in the Spring of next year, I would be grateful if you could offer some suitable dates so that I can start planning things from our end. Clearly, a number of researchers will need to travel from overseas, and I would be grateful if you could indicate the budget for this meeting. I will be in touch with you in the near future with regard to proposed speakers, titles, etc.”
Then if we go on to page 629, Sir Kenneth writes back:
“Thank you for your letter of 13 November enquiring about the dates for the meeting that I wish to convene.”
He gives a provisional date of Monday 23 March with the whole day set aside.
“The purpose of the meeting is for me to hear the scientific information, both for and against the role of measles virus and measles vaccine in inflammatory bowel disease. The agenda items will cover the epidemiological associations for measles virus and measles vaccine with inflammatory bowel disease and the virological evidence in addition. I see this as an opportunity to hear the arguments and to take part in the debate which will be in the form of presentations followed by opportunities for discussion. I do not anticipate a need for researchers to be travelling from overseas for this meeting.
An outline agenda ….. and further details of the arrangements ….. will be sent ….. as soon as possible.”
If we go on to page 635 we see what Dr Wakefield had to say about that. This is a letter from him to Sir Kenneth dated December 97, I think it is the 18th. He acknowledges the provisional date, but he then says:
“There appears to be some confusion as to the structure of the proposed meeting, and I hope that we can clear up any misunderstandings. I agreed to organise the Agenda for the meeting on behalf of the Inflammatory Bowel Disease Study Group and its collaborators. You have indicated that the meeting will provide you with an opportunity to hear all of the scientific information; without the attendance of workers from other centres around the world, this would not be possible. I would not be qualified to present their data.
The workers who would need to be present include”,
and then he names an Emeritus Professor of Microbiology from Japan, from Wakayama, a Professor Kawashima from Tokyo Medical College, a doctor from Turin, a professor from Stockholm, two doctors from the Mayo Clinic in Minnesota and one from Argentina, and he also wanted someone from Zurich to give a talk on biological plausibility and said:
“his contribution would be essential to bring ….. understanding to the complex issues that arise. I am sure that there are a number of workers that you would wish to invite who have failed to identify measles virus in inflammatory bowel disease. Without all these workers present, the meeting would be of little value. I am not prepared to provide the Department of Health with another opportunity to dismiss the findings of my group and those of others on the basis of an abbreviated and incomplete presentation. This would, no doubt, provide a further opportunity for reassuring the media that you have taken this issue sufficiently seriously and considered all the facts when that is, in our opinion, far from being the case. I have been in this situation with members of the Department of Health before and I will never get into it again.
Therefore I will be ….. grateful if you could indicate a budget for this meeting so that I could go ahead and invite the aforementioned speakers and proceed to arrange our side of the agenda.”
There are copies of that letter sent to Miss Tessa Jowell, Professor Pounder and Professor Walker-Smith. Did that meeting in fact ever take place, Professor Salisbury?
A Yes, it did take place, but it did not take place under the aegis of the Department of Health. What became clear as this correspondence was progressing was that we needed to try to find a forum that was not going to lead to the sorts of dissatisfactions that clearly were already being expressed, and Sir Kenneth Calman therefore decided to ask the Medical Research Council if they would take on the arranging of the meeting, they would identify the individuals who were to be invited and they would basically organise the event. The MRC then took on the arrangements for providing the place for the meeting, a chair, the speakers, the presentations and we did not arrange that meeting.
Q I think chronologically before that meeting, that Medical Research Council meeting, in fact took place, which I think was in March 1998, The Lancet paper, the paper which investigated the link between inflammatory bowel disease and developmental conditions, disorders, was published in February 1998.
A That is correct.
Q If we go to page 647, please.
A Is it 646 rather than 647?
Q Yes, it is . You are quite right. Thank you. This is to Sir Kenneth Calman in fact from Professor Pounder:
“Further to my letter of the 30th July ….. and your reply of the same date ….. I am writing on behalf of Mr Andrew Wakefield and Professor John Walker-Smith to inform you that the above paper is now in press.”
I should have read out that the title was “Re: Ileal Lymphoid Nodular Hyperplasia, Non-specific Colitis and Developmental Disorder in Children: A New Syndrome?”.
“It describes the detailed clinical and pathological examination of 12 children with a regressive developmental disorder and an unusual form of inflammatory bowel disease. We do not know the precise date of publication, but it is likely to be in the near future.
The Royal Free Hospital and School of Medicine plans to hold a press briefing on the day prior to publication. Our sole aim is to attempt to ‘educate’ the lay-press, so that the reporting is accurate and not sensationalist.
As I say in my letter of the 30th July 1997, in the past we provided you with full information of our research in advance of publication, but we did not appreciate your press conference held two days before the paper appeared.
Would you like a copy of the paper, on the understanding that it is embargoed until the day before publication?”
Was it agreed that it would be provided embargoed?
A Yes is the answer because the next letter makes it clear that we do receive the prepublication draft. It was very difficult for us because clearly we were being asked very specifically not to make any form of statement until the time of publication or thereafter. That meant there would be no opportunity for alerting health professionals in any way about the publication in advance. I had spoken to Professor Zuckerman about the intention to hold a press briefing and much play was made that this was a press briefing, not a press conference. I felt this was naïve. I did not believe that anybody would know the difference and whatever the intention this would be a press conference.
Q The last letter that I wanted to take you to in this series is at page 647 again from Professor Pounder to Sir Kenneth Calman:
“Dear Sir Kenneth
With this letter I enclose a prepublication copy of the manuscript “Ileal lymphoid nodular hyperplasia, non-specific colitis and developmental disorder in children: a new syndrome”. This is provided to you on the express understanding that you will respect our embargo about discussing it in public until the Thursday before publication. We have also provided Sir David Hull with a personal copy so that he can be fully informed.”
Would that be Sir David Hull in his capacity as the chairman of the JCVI?
A Yes, I imagine that was.
“We undertake to tell your office of the precise date of publication together with the arrangements that the Royal Free will make for the press briefing.
It seems likely that at least some members of our team will recommend that there is a switch from MMR to monovalent vaccination to ensure that the measles vaccination programme continues (excluding only those with a family history of inflammatory bowel disease or autism). We believe that there is only a limited amount of monovalent measles vaccine available at the present time and your department may wish to investigate this potential problem.
Please let us know if there is any supplementary information that you require.”
Those last two letters emanate from Professor Pounder. What was your understanding of his involvement in this particular paper?
A We understood his involvement in the past because he had been involved in the Crohn’s disease measles vaccine work. We did not understand what his involvement was in this work. He was not to our knowledge an expert in autism or vaccines and we did not know quite why he had chosen to send these two letters.
Q As far as the embargo is concerned you have already touched on this, Professor Salisbury. By that time were you expecting there to be a degree of media interest?
A I think we had no doubt that there would be.
Q What did you anticipate that the effect in broad terms of that media interest would be on the general public?
A We saw this as distinctly threatening in terms of creating public anxiety over safety of MMR.
Q Had it not been for the embargo that was put on the paper would you have taken some sort of anticipatory steps as you had previously?
A I think that is hypothetical, is it not, because the embargo was there in the correspondence. What it did is it took away the opportunity for us to have at least made some attempt at informing health professionals in advance that there was going to be this publicity and they would need to deal with parental anxieties.
Q Accompanying this letter, turning to page 648, is a prepublication copy of The Lancet article.
A Yes, I have that.
Q It goes on to page 673. Was it your understanding, Professor, that that was how The Lancet paper was going to appear in The Lancet in that form?
A Yes. We had been told that this was the prepublication copy. It was not a proof version but, nevertheless, we had to assume that this was what The Lancet was going to publish.
Q You say that you were aware of the press briefing that it was planned would take place. Did you subsequently become aware of the date of that which was the date before the paper was ultimately published?
A Yes, clearly we knew that The Lancet was going to press release the article as well.
Q Is it correct that you did not attend that press briefing but that a member of your department did?
A It is correct that I did not attend and I do not believe any member of the department attended. I think Joanne Yarwood, who was employed at the time by the Health Education Authority, attended.
Q I should make it clear, Professor Salisbury, that I am not asking you to embark on the science relating to The Lancet paper but I do want to ask you overall what was your reaction? Presumably you read this copy when it came prior to publication?
Q What was your understanding of what was important in that paper in broad terms? What was it trying to get over?
A The paper, in my view, was trying to do a number of things: it was trying to report a new syndrome that children with autism had a previously unreported bowel condition. It was then trying to link somehow the receipt of MMR vaccine into that scenario and I felt that it failed miserably in doing that.
Q Those are obviously two different aspects. When you read it did you gain any impression as a reader to which was in the ascendancy?
A Do you mean which of those two parts?
A No, it was very difficult to make a judgment as to which of those two. One of them appeared to be an observation on which the group believed they had objective evidence – that was of the bowel condition. The link with the vaccine was bizarre to anyone that knew about vaccines.
Q That is obviously a subject upon which you have a very considerable degree of experience and expertise. Were you concerned about what message the media would take away in relation to this paper?
A We were very concerned because we felt very much that the message the media would take away was the MMR message. I think there are some other elements of this paper that also gave cause for great concern, certainly to me, and there were a number of errors that were pointed out in correspondence subsequently in The Lancet but there were some others that were not and they are important.
Claims were made about associations between MMR and autism, quoting references that were incorrect: the work of David Miller was quoted here and it was misleading. But what really concerned me was reference to the work of Hugh Fudenberg because by this time I knew quite a lot about Hugh Fudenberg and his claims about autism and vaccines. We had previously ---
MR COONAN: My learned friend knows full well that this is straying into areas that this witness should not be taken to and, if I may say, the witness also should know, but so far my learned friend has not intervened and she should have and that is why I am intervening.
MS SMITH: I asked a question and I made it perfectly clear and I know that Professor Salisbury understands that I am not asking him to express any detailed scientific views in relation to the scientific content of The Lancet paper but it seems to me it is not a question of the question that I asked him but he is perfectly entitled to tell the Panel in broad terms, and with that restriction that he should not embark on the science, why he had concerns in relation to the paper.
MR COONAN: Sir, this witness, as I understand it, is not being called to deal with any critique at all of this paper, least of all a critique based upon his view about contributors to the learning and to the science which may have underpinned this paper. This witness is here principally to set out the chronological steps which he has done thus far. At this point we appear to be embarking upon a dissection of the paper from his standpoint. That again and I carefully indicate, Legal Assessor, that this witness’s evidence is to be very carefully bounded. At the moment, unless this is properly circumscribed, we are going to get way beyond the understood area of his evidence.
MS SMITH: This witness is, after all, the head of Immunisation and he has told us that he had considerable concerns about the message that would be taken away by the media and the public in relation to this paper. It is perfectly proper that he should give that evidence. What precisely he was going to say we have yet to find out of course, but he was simply elaborating on why he had those concerns in relation to any message associated with the MMR vaccination that might be carried away by the media and by the public. It was for that reason that I was asking him those questions because those matters are directly relevant to the charges which these doctors face. They were prefaced, and I know that Professor Salisbury understands that he is not here as an expert dealing with the actual scientific content of the paper.
THE LEGAL ASSESSOR: I have a copy of the redacted version of the witness statement and it seemed to me quite clear that he was straying into areas where there has been obvious agreement, or I understood there had been obvious agreement, that he would not give evidence in-chief about those areas. I for my part on your behalf was expecting him to be moving on to the effect on the national immunisation programme about which he can give factual evidence. He is not here as an expert and he was straying into areas which are quite clearly, I thought by agreement, had been excluded from his evidence.
MS SMITH: We do not yet know what the answer to the question is going to be. I take the point that Professor Salisbury is not giving evidence about the scientific contents in The Lancet paper but if he has told us that he has concerns about the message that is being taken away by the media in relation to MMR that is clearly within the evidence that he has been called to deal with and it was for that reason that it seemed to me to be appropriate at least to enable him to give that information in broad terms. If he strays further into the detail – he will forgive us talking about him as though he is not here – then it is obviously inappropriate.
THE CHAIRMAN: My understanding from Professor Salisbury’s response was about the concerns that he had from the paper, so in a way it is kind of a critique of the paper, but I will leave it to the Legal Assessor to adjudicate on this issue whether we should go along this road or not.
THE LEGAL ASSESSOR: My advice to the Panel is it should not receive evidence from Professor Salisbury about his views for the false premises in the paper and that he should proceed now to deal with the public perception of that paper about which he can speak and the effect it had on the national immunisation programme. That is my advice.
THE CHAIRMAN: Ms Smith, now we have the decision, I wonder if you could go on that route, please?
MS SMITH: With the greatest respect to the Legal Assessor, I am quite prepared to go on to another topic but I am not actually going to deal with the public perception in relation to The Lancet article for a moment not least because it will take considerably longer than fifteen minutes. I am going to ask Professor Salisbury to deal with a totally separate more circumscribed topic and then I will deal with that last issue, if I may, tomorrow morning.
(To the witness) Professor Salisbury, I want you to deal with a topic which arises out of the correspondence which was received in 2002 by Sir Liam Donaldson, who was then the Chief Medical Officer, from Dr Spratt who was a consultant paediatrician to one of the children in the 1998 article and, as I say, we will come back to the paper tomorrow morning.
Those letters start in FPT3 and page 1140A which is a letter to Professor Donaldson. I should make it clear that I am going on way beyond because this is a separate topic and I want to deal with it now and then we will revert to the effect, if any, on the immunisation programme tomorrow morning. This is a letter that is way on in 2002, so some four years after the publication of The Lancet article, and it was a letter from Dr Spratt to Professor Donaldson and we see a note on it that it was urgently copied to you.
“Dear Professor Donaldson,
I chanced to hear on a BBC news bulletin over the weekend that you have proposed an independent reassessment of (presumably) all of Dr Wakefield’s research into the association of inflammatory bowel disease, autism and MMR, in certain children; and I simply hope it is true.
To the best of my understanding one of the original twelve patients making up the materiel for his first paper in the Lancet four years ago – probably ‘child nine’ – was my specialist responsibility locally; and at least in that child’s case, and in my view, the apparently innocuous claim that he was ‘… referred to a paediatric gastroenterology unit …’ is essentially misleading. The more inglorious reality is that following a shambolic interlude involving a since discredited doctor at another London hospital, which business was also scarcely my doing, I was approached out-of-the-blue by a trusted colleague in September 1996 – largely it was acknowledged on Dr Wakefield’s behalf – and was asked to allow him (my friend) to see the patient and to advise. I saw him as a potential white knight and agreed.
In due course he obliged – and not to my surprise found very little amiss. An inconsequential history and no physical signs. However, expressly in the light of Dr Wakefield’s theories, and without further reference to me, or it must be said any particular conviction of his own, he yielded to parental pressure to arrange the investigations specified in the Lancet paper. That was it: it appeared to have been almost ordained, and the rest followed. More or less as described – although my colleague’s later correspondence did not impart the same medical confidence as the subsequent publication.
Ah well – going back to the first two sentences of Dr Wakefield’s paper I just wonder how he came by his twelve no doubt utterly distressed volunteers, and whether or not the heavy socioclinical bias which informed the attitude of my patient’s parents might have been repeated in any of the other eleven families. In a retrospective assessment of the work of the Royal Free group I would see these points as amongst the first questions to be addressed. My own interest is declared.”
The response to that appears to have been a telephone call from you because, on page 1141, there begins a letter from Dr Spratt, this time addressed to you rather than to the Chief Medical Officer, and we see at the start,
“Thank you for your further call about ten days ago.”
Are you able to recall the sequence of this for us at all?
A Yes, of course. What I think had happened was that this was February 2002 when we were coming under intense media pressure following the publication of an article in the Journal of Molecular Pathology purporting to show the presence of measles virus in the bowel of autistic children. We were all doing a great deal of media work but Liam Donaldson had done, I believe, television on a Sunday morning and it must have been that report that Dr Spratt had seen that provoked his letter to Liam Donaldson on 19 February. The CMO asked me if I would contact Dr Spratt and get a little more information and I phoned Clifford Spratt and received thereafter his letter to me of 22 March.
Q As far as that letter was concerned, he says,
“Thank you for your further call about ten days ago. …
I have also taken time to look up aspects of [Child 9]’s vintage history. I saw him first at 2 years 3 months …”
and he then sets out something of the history and I am going to leave the Panel to read all the details of this letter but, just going through it briefly, there is a reference to him having secondary autism and to a referral to Chris Rolles’s team in Southampton and that the parents were not persuaded about Child 9’s diagnosis. Causation was not an issue in their understanding of his case. Then there were problems about the child’s hearing and the parents thinking that that was the reason for the developmental delay.
“A very comprehensive autism assessment followed the next month, again in Southampton, this time with [Dr Rolles]’s full team mustered …”
and confirmation made that the child was autistic.
“Numerous sensible recommendations followed – but again there was no mention of causation”
and a reference to German measles at 11 months of age which was never corroborated. He says,
“Thereafter a lull ensued with me and my next involvement was a call from [Child 9]’s mother in September 1994 – to say that following enquires of her own, which had involved contact with an apparently very distressed mother … [Child 9] had been taken to see Dr Bhatt at the Chelsea and Westminster Hospital … and that [Dr Bhatt] wanted [Dr Spratt] to authorise further investigations, in his laboratory, to confirm a diagnosis of Vitamin B12 deficiency.”
He says that there was a good deal of to-ing and fro-ing but he could not establish a working understanding with Dr Bhatt and, in the end, there was a referral to Dr Cavanagh who was the paediatric neurologist at the Chelsea and Westminster. Dr Cavanagh saw the child in February 1995.
“He did not refer to causation directly – but did say that [Child 9]’s mother had noticed a strange smell to his urine … and concluded that Vitamin B12 investigations were the priority at that stage.
Later, in March 1995, Dr Bhatt said the boy had a cobalamin deficiency – of uncertain aetiology …”
and advised more investigations.
“These followed and in November 1995 Dr Cavanagh confirmed ‘his’ view that [Child 9] was unable to absorb cobalamin in food. He mentioned onward referral to Professor Walker-Smith – but as I was no longer seeing [Child 9] at that stage, and correspondence was no longer being addressed to me, I did not take any further action at that time.
So much for the introductions. John Walker-Smith wrote to me (…) to invite [Child 9]’s referral to his service on 11th September 1996; and I replied positively a fortnight later. At that time I did not know anything about Dr Wakefield – but I knew, liked and was very much inclined to trust John personally. I still do and regard him as a personal friend. Taken at face value his letter, and Dr Wakefield’s credentials on the research protocol, read well to me at the time. In a sentence: I took John’s introduction to be a good enough guarantee and notwithstanding the information that [Child 9]’s parents had signed-up to Dr Wakefield’s protocol in advance I agreed to abide by his (John’s) view of the case.”
He said that he was wary of the involvement of another doctor who had been in collaboration with Dr Bhatt, and he says that he wrote about the connection with Dr Bhatt to Professor Walker-Smith separately and privately at the end of September 1996.
“You may consider the key letters John’s to me of 11 the September and 8th November 1996. By that stage [Child 9] had become profoundly autistic, and indeed may well have had one unremarkably loose stool some days. I do not think every day – nor do I believe that whether or not he had abdominal pain there was any blood or mucus present in stool. John does not say so either, and as described [Child 9] was otherwise a well-built and robust child, without any clinical signs of gastrointestinal disease.
By all accounts no simple stool or blood tests were carried out and it seems the indications for further investigations were the combination of autism and gastrointestinal symptoms, and the 100% diagnostic yield on colonoscopy in up to eight other similar children seen at the Royal Free Hospital. Plus, presumably crucially (the word ‘therefore’), the enthusiasm of [Child 9]’s parents to proceed. Rather strangely, it strikes me now, with any reference to Dr Bhatt’s diagnosis of Vitamin B12 malabsorption.
Again in confidence I enclose copies of the relevant letters and reports from the end of 1996, and early the next year. The suggested trial of mesalazine proved ineffective – no markers, really – and the lead overload, which was discovered semi-accidentally, was eventually attributed to his PICA and appetite [for] very old paint and wallpaper. No one suggested it might have caused abdominal pain, or anything else (e.g. terminal ileal histology!), and I was advised that the blood level (…) was not clinically significant. It has waned since.
Clearly [Child 9]’s story, and his very likely inclusion at ‘Child 9’ in Dr Wakefield’s paper in the Lancet in 1998, is open to different interpretations”
and he then sets out some references to the characteristics of the parents which I will leave you to read for yourselves.
“It is clear that the idea the boy might have MMR related inflammatory bowel disease arose at the Royal Free, and is attributable to the dissemination of Dr Wakefield’s views there. John said originally that he was ‘neutral’. I have to say my own view would have been more sceptical, but my main quibble now would be with what I have read as Dr Wakefield’s blandly implied claim that [Child 9]’s referral and investigations occurred in the ordinary course of clinical events.
I do not believe that that is reasonably true in this boy’s case. I was not impressed by Dr Bhatt’s data in 1995; and it would not have occurred to me, spontaneously, to refer him to a gastroenterologist – especially for a series of invasive investigations at that time. The fact that Nick Cavanagh recommended John Walker-Smith in November of that year, and that John confirmed he had heard about [Child 9]’s case from Dr Wakefield in September 1995, or before, and the coincidence of Dr Linell” who is the doctor who worked with Dr Bhatt “suggests to me the possibility of a working liaison between these hospital departments.
Whilst earnestly requesting the protection of continuing confidentiality between ourselves I hope this information is helpful to you.”
Enclosed with that letter, if we go to page 1146, is the scientific protocol from Dr Wakefield’s department that I asked you about earlier in relation to the distinction between MR and MMR; is that correct?
A Yes, this was the first time I had seen this protocol.
Q That was sent to you by Dr Spratt in 2002.
Q Attached to that also were extracts, I think it is right, from the medical records of Child 9 and they go on to page 1145; is that correct?
A I think they go way beyond that.
Q Yes, they do. Hang on, I will find you the correct number. Actually, if you would go to page 1145 for a moment, that is the referral letter which Dr Spratt refers to in his letter to you, the first letter in the correspondence dated 11 September 1996; is that correct?
A Yes, that is correct.
Q There is a response to that – and again these are all in the child’s medical records, but just so that we know where they are – at page 1167 which is Dr Spratt’s letter back to Professor Walker-Smith; is that correct?
A Yes, that is correct.
Q Then, they go on in total to page 1196 and we see in that last letter on page 119 a manuscript note which we know was included on 18 March 2002 saying,
“I have no records to suggest this consultation took place”,
that was the final consultation referred to in that letter.
“The trail of correspondence with the Royal Free ends at this point.”
Is that correct?
A Yes, that is correct.
MS SMITH: Sir, I do not know how vital it is for me to stop at 4.15. I have two more very short matters to refer to.
THE CHAIRMAN: I think that it is fairly important. I believe that one of the Panel members has to go a very important meeting and it is because of that that she has requested that we rise early.
MS SMITH: I do understand and, in that case, perhaps I can pick up with those last two letters in the morning and I know that Mr Miller has some correspondence in relation to this same issue that he wants to produce as well. So, we can perhaps do that tomorrow morning.
MR MILLER: Sir, I think I told you on Friday that there is a bundle of correspondence which complements this which is put in because Dr Spratt will not be being called as a witness and I will deal with that after Professor Salisbury has finished giving his evidence.
THE CHAIRMAN: Thank you very much, indeed. We will now adjourn and resume the hearing at 9.15 in the morning if that is acceptable to you all. (Agreed)
(To the witness) Professor Salisbury, I have to give my usual reminder once again that you are in the middle of giving your evidence and are still under oath and therefore, please, do not discuss this case with anyone overnight including any of the lawyers. We will see you tomorrow morning at 9.15.
(The Panel adjourned until Thursday 23 August 2007 at 9.15 a.m.)