Tuesday, January 31, 2012

Day 3 GMC Fitness to Practice hearing for Andrew Wakefield

GENERAL MEDICAL COUNCIL

FITNESS TO PRACTISE PANEL (MISCONDUCT)



Wednesday 18 July 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




CASE OF:

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


(DAY THREE)



(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




Page No


OPENING SUBMISSIONS by MS SMITH contd. 1






THE CHAIRMAN: Good morning everyone. First of all, can I thank you again for being here this morning?

There are a couple of housekeeping matters, if I may go through them very quickly. First of all, it has been brought to my notice that Ms Smith’s room is on the floor below, which means that, although Ms Smith is just about coping I think she is finding difficulty with a 15 minute break to go up and down and have a cup of tea and take a comfort break and maybe see one or two other people as well during that break, so can I suggest that from today onwards rather than a 15 minute break we actually have a 20 minute break for the mid-morning and mid-afternoon breaks. I hope that is acceptable to you all.

Secondly, one of the panellists has to attend a very important meeting tomorrow morning, which actually means that we will be starting somewhere between 11.00 and 11.15, but we will make up some of that time. Again, if it is acceptable to you all, I think we can shorten our lunch break to about 45 minutes and sit at least until 5.00, again, depending on where the natural break comes. Once again, I hope that is acceptable to you all.

Can I now ask Ms Smith to continue?

MS SMITH: Thank you for that, sir, and I will now resume my opening.

First of all, if I may, with a very quick recap so that you recall where I am up to in what is rather a long and complex story: I told you yesterday about the ethical background to this case and about the ethics committee application for project 17296, and the assurances that were given to the committee that the investigations were part of the normal clinical care of these children, and also about the stance that Dr Pegg, the chairman, took as a result of that assurance, that ethics committee approval was given for the invasive investigations that were carried out, and I am going to analyse now where that position and the information and documents that I referred you to yesterday takes us.

It is our case, as I said to you yesterday, that as the responsible consultants, all these three doctors had a duty to ensure not only that the information provided about the study was accurate but that the project confirmed with the stipulations that had been laid down by the ethics committee.

We are going to be studying during the course of this case, in considerable detail and in my opening later in some detail, 11 of the children who were part of project 17296, and who were ultimately written up, along with one other child, the 12th child, who is a child from the USA for whom we have no records, in a scientific paper for medical journal.

I want to preface the general remarks that I am going to make about the case histories of those 11 children with the warning that generalisations inevitably carry inaccuracies. All these children had different case histories, and later in this opening I am going to be telling you why it is that each child, we say, was investigated inappropriately and without ethics committee approval.

You are going to be hearing detailed criticisms from the two experts who we are calling, Professor Sir Michael Rutter, who I mentioned to you yesterday, who is a consultant child psychiatrist, and Professor Ian Booth, who is a consultant paediatric gastroenterologist. For present purposes though I want to make some generalisations with that caveat: we say, on the basis of the expert and the factual evidence that we are going to call, the first point, as I have said before, this was a research project. The investigations were not, save in a very few exceptions, clinically indicated for the children upon whom they were undertaken. They were highly invasive, unpleasant tests which certainly qualify as high risk under the guidelines relating to children and they were done for research purposes as part of a research project. Because of the misinformation that was given to the ethics committee, they were done without the only thing which would have made them acceptable, that is ethical committee approval after proper scrutiny by an ethics committee. Whether the committee would in fact have given permission for such invasive tests for research purposes, given the restrictions that I have taken you to on research on children, and given the disquiet that I referred to yesterday expressed by one member, must be in some doubt, but it is irrelevant to the matters that you have to consider. The fact is, we say, that this committee was deprived of the opportunity properly to consider the question of whether they would give ethical approval or not for this as a research study whatever their conclusion may or may not ultimately have been.

In support of our contention that this was a research project we rely on both the factual context as I have described it to you and as you will see set out in the medical records of these children, and on the views of our experts.

As is apparent from the details I have referred you to in the ethics committee application, these children were admitted for a planned and standardised set of investigations, the most invasive being, of course, the colonoscopies and the lumbar punctures over a timetabled stay. The views of the experts whom I shall be calling are that the tests they underwent were not, in the vast majority of the cases, dictated by their presenting clinical conditions, and the purpose for doing them must therefore have been research-driven. For example, the gastro-intestinal symptoms from which they suffered were of varying degrees, most were minimal, in some cases they were non-existent at the time they were seen at the Royal Free, or they were not of a type which suggested inflammatory bowel disease, or which justified resort to invasive investigations such as colonoscopy as a first step.

As I say, I am going to revert to those issues when we look at their individual cases. The second point we make is that the children who formed part of what we say was a research project did not meet the inclusion criteria that had been set out to the ethics committee when the application was made. They did not conform to the description of the research subjects contained in the application, and that was integral, we say, to the whole basis of project 17296. If they did not conform to that description they did not qualify for the study. None of them had in fact had the MR vaccination. Only one had had the measles vaccine. On the contrary, all of them had had the MMR vaccine. None of these children had at any time a diagnosis of what you will recall I told you was a very rare disorder of disintegrative disorder. Most were diagnosed with some form of autism of varying degrees of severity.

The third point is that the majority of the conditions which were set down by the ethics committee were not complied with in the majority, if not all, of the 11 children whom we are going to be looking at. That is, seven of the children included had been seen before the start date, which was expressly provided by the committee – and you will remember they gave a start date of their last meeting when approval was ultimately given – 18 December 1996. That is not a quibble or a mere contravention of a formality. You will be hearing from the chairman of the committee that it is highly relevant to the issue of consent because the committee does not allow or approve of backdated consent. In other words, they, the committee, have had to approve the consent forms and the consent then has to be taken on the basis of that approved form of consent prior to the procedures being carried out, so it is an important stipulation.

So far as the consent forms are concerned, we do not know if it was modified as the committee had required because the requirement that it was to be filed in the patient’s records, which you will recall was a requirement by the Royal College of Physicians in general terms in relation to research consent forms, and was also a specific requirement by Dr Pegg and his committee, was not complied with in 10 cases of the 11 we will be looking at. In the remaining case the complete records are unavailable. It is not in those records that we have.

The parents in this case, with the exception of the mother of child 12, to whom I am going to be referring later as “Mrs 12”, are not going to be giving evidence, and it is not part of our case that they were anything other than content with the investigations which were carried out on their children. Indeed, as you will be hearing, some of them positively encouraged those investigations to be carried out, but in the last analysis it must never be forgotten that the patient is the child. Had the consent forms been preserved as they should have been, the nature of the information that was given at the time, in particular, in relation to the key matter about which the ethics committee had expressed concerns, namely clarification as to whether or not the investigations were part of normal care for that child, would be ascertainable from the child’s records, as it is they are not. As I say, I have referred to consent forms as a composite term but it covers both the consent form and the patient information sheet that goes with it, both of which you will recall are appended in a proforma to the back of the ethics committee application but which are not in the individual child’s records.

The difference between the children that it was envisaged would be part of the project and the children who were in fact investigated is significant. Again, it is no mere formality. There is a very real distinction, particularly as to age, between the cohort of children who had the MR vaccination, who you will recall I told you were school age children aged five to 15 and those who had the MMR vaccination, and it is our case that it is inconceivable that these doctors were not aware of that distinction. In addition to that, there is a very real distinction between disintegrative disorder and other forms of autism, and, indeed, you will recall that that distinction was expressly acknowledged and drawn to the attention of the ethics committee in the ethics committee application.

So, those are the main points in relation to what I told you of yesterday. Some considerable time later, as you will be hearing later, the research relating to these children was written up in a scientific paper which was submitted and ultimately published by journal. I am going to be looking at that paper later in some detail. Its relevance at this juncture is that contained in that paper was a heading “Ethical Approval and Consent” and under that heading, “Investigations were approved by the Ethical Practices Committee of the Royal Free Hospital NHS Trust.” All these doctors are charged with making that statement, which we say was plainly wrong, given that they were all well aware of the representations that they had made that the investigations were part of normal care and thus did not need ethics committee approval. Despite that, article expressly says, “These investigations have been approved by the ethics committee.” That statement in , which was in 1998, led to the whole issue of ethical approval being raised in July 1998 by Professor Sir David Hull. He is going to be a witness in this case. Until his retirement he was the professor of child health at Nottingham, and between 1991 and 1994 he was president of the British Paediatric Association. During that time that organisation had produced the guidelines for the ethical conduct of research involving children, which I referred you to yesterday, and when we go back to look at those when Professor Hull comes to give his evidence you will see that he wrote the introduction commentary to those guidelines.

In July 1998 he wrote to the dean of the Royal Free Medical School, in a purely personal capacity, to express his concerns because it was his understanding that the research was continuing and he wanted to know what the ethics committee’s position on this particular series of investigations was, and he wrote, as I say, to the dean, who is Professor Zuckerman, from whom you will also ultimately be hearing, and the letter that he wrote is in bundle 3 at page 928. It is dated 6 July. The letter from Professor Hull to Professor Zuckerman reads as follows: “Dear Professor Zuckerman, Re Investigation of children with pervasive developmental disorder for bowel disorder”, which was the title that, as you will see the research was ultimately written up in :

“I would welcome your help on a matter of personal concern. In February 1998, Mr Wakefield and his colleagues reported the findings of their search for the cause of bowel disorder in children with autism. At the MRC [Medical Research Council] meeting on MMR they said that many more children had been similarly investigated and still more were on the waiting list. The studies include: admission to hospital, sedation, lumbar puncture, biopsies of the bowel, MRI imaging and radiography.

In the light of the initial findings and the evidence that as a group the children do not suffer long-term bowl disorder, it would seem difficult to justify such invasive studies on clinical grounds. It may be that there are arguments to perform further investigations to elucidate the nature of the brain disorder and the bowel findings. As I cannot see what those might be, the thought of autistic children being subject to such investigations continues to trouble me, and thus my request to you.

I see that the investigations were approved by the Ethical Practices Committee of the Royal Free Hospital NHS Trust.”

– that is a quote from the paper –

“If the studies are continuing I would be grateful if I could see the Ethics Committee position on the investigations, especially if they have reviewed their position in the light of the reported findings. If you thought it helpful the Ethics Committee of the Royal College of Paediatrics and Child Health could give an independent view.”

So, thus, the thrust of Professor Hull’s letter related to the ongoing investigations subsequent to the children, written up in article, whom he noted already to have ethical approval, but the point is that it triggered the dean, Professor Zuckerman, to inquire into the ethics position from the outset of the study, and he raised the matter with Dr Pegg, the chairman, and Dr Pegg wrote to Professor Zuckerman in a letter at page 951 in the same bundle. This is July 1998:

“Dear Professor Zuckerman”,

and he refers to the title as it was in the original ethics committee application at the top of the page, and this is of course Project 172-96,

“The above application was first considered at the ethics committee on [13 November 1996]. The committee was very conscious of the requirement to avoid non-therapeutic research of more than minimal risk in young children.”

That, of course, is a quote from the guides that I have read out to you.

“We therefore asked for reassurance that the investigations that were to be carried out in this study were clinically indicated and were not being carried out just for research. Professor Walker-Smith gave me that written reassurance”.

He then quotes from the November 1996 letter that I read to you late yesterday afternoon:


‘I can confirm that children would have these investigations even if there were no trial’

Thus at the ethics meeting in December there was no real ethical issue to address. The children were having the investigations as part of normal clinical practice and the ethics committee was involved purely because the cases were being collected for report by publication. The study was therefore approved.

On [22 July 1998] the ethics committee”,

so that is very recently, this being 24 July 1998,

“reviewed the study again, following a report by Professor Walker-Smith. The study was now titled” – and he then gives the title – “‘Autism and Non-Specific Colitis and Lymphoid Nodular Hyperplasia’. Again, Professor Walker-Smith gave us reassurance that only clinically indicated investigations would be carried out”.

So that is a reference subsequent to investigations. He then quotes that letter from Professor Walker-Smith:



‘I would like formally to request Ethical Committee approval for our clinical research analysis of these children who ….. are continuing to see’,”

and I am sure Professor Walker-Smith would accept that he meant “to be seen”,



‘by clinical need’.

Again the ethics committee approved the study on the undertaking that all that was being approved was data collection.

On 9th July you wrote to me for my comment on the letter of Professor David Hull. In his letter Professor Hull states:

‘I see that the investigations were approved by the Ethical Practices Committee of the Royal Free Hospital NHS Trust’

This is, of course, incorrect. We did not approve the investigations. We approved data collection from clinically indicated investigations. It is not, at present, the role of an ethics committee to question clinicians judgement as to what are and what are not clinically indicated investigations. However we do not just take the word of the investigator, rather we ask for independent expert review of all applications. In this case Dr Owen Epstein” – who was another gastroenterologist at the Royal Free – “provided a review of the project and I have a letter from him ‘strongly supporting’ the study.

I hope I have answered all your questions regarding the ethical review of this study.”

Now, that letter, we say, clearly summarises the Ethics Committee’s position on the basis of the clear assurance originally given that the investigations were clinically indicated.

Professor Hull remained concerned about the issue since, you may think not unnaturally, he struggled to understand why it was that Dr Pegg said that the Committee did not approve the investigations and paper had said that they did, but in effect he concluded that he must let the matter rest, and there it did rest until the events (which I am going to deal with later) which led to an investigation by journal and ultimately to this hearing today.

I am now going to turn to a totally different issue in order to paint in the background of this case so far as Dr Wakefield only is concerned, and that is the background of the litigation, which is a matter which does not concern the charges against either of the other two doctors.

During that same period in 1996 Dr Wakefield was engaged in advising a solicitor, Mr Richard Barr, who was a partner in a firm of solicitors called Dawbarns in King’s Lynn in Norfolk, with regard to proposed litigation in relation to the MMR vaccine on behalf of a large group of claimants who were claiming to have suffered damage from the administration of that vaccine. Dr Wakefield’s involvement in the litigation arose as a result of his assistance to the claimants’ solicitors and of his being granted a sum of money by the Legal Aid Board as part of their funding of the group of people who proposed to litigate in respect of the damage they believed that they had been caused by vaccination. Dr Wakefield was granted a sum of money to be used on research to see if a causal link could be established between the vaccine and the damage that the claimants alleged to have suffered from. It is our case that that money was granted to fund part of the project that I have been describing to you, Project 172-96.

Now, I am just going to remind you of the charges in respect of Dr Wakefield, as you heard them read out, arising out of the involvement in that litigation. Firstly, he has been charged with the dishonest misuse of the money, because he did not use it for the purposes set out in his costings for the Legal Aid Board but used it instead for general research purposes, and in those circumstances the charge is that he misused public funds. Secondly, he is charged with failing to tell the Ethics Committee either about his very close involvement in the litigation on behalf of the claimants or about his receipt of funding from the Legal Aid Board, as we say for part of Project 172-96, although those matters should, we say, have been disclosed because they were relevant to the Ethics Committee’s consideration of the project and they involved potential conflicts of interest. Thirdly, he is charged with failing to reveal subsequently to the editor of , when he submitted to journal reporting the results of Project 172-96, his involvement in the litigation and the Legal Aid Board funding, and again we say those are matters which should have been disclosed because they involved potential conflicts of interest. In addition, a declared source of funding in the paper, which I shall be referring you to later, should have been accurately stated.

So what I am going to try and do now is to tell you first of all a little bit about the chronological background to the litigation and then deal with the charges relating to what we say was a misuse of the Legal Aid Board public money.

First of all, the Legal Aid Board, as you may know, was the predecessor organisation to what is now called the Legal Services Commission, and if I interchange those two terms I apologise for it, but that is why, they are the self same organisation, and they are in charge of the public funding of litigants. Solicitors submit to them proposals for which they seek legal aid funds, and they are then considered by an in-house legal aid lawyer, and the lawyer has to make decisions within the statutory framework as to whether legal aid should be granted. There are two principal tests, you will be hearing the lawyer from the Legal Aid Board tell you, which they have to apply; whether the proposed case has got any merits, and whether there is a favourable costs benefit ratio, in other words whether the cost of the case is proportionate to the benefit, usually the damages, which might ensue if it is successful. If those tests are satisfied, and if in addition the litigant is eligible on the grounds of means testing, then he is granted legal aid, and from then on that is kept under scrutiny between the solicitor and the Legal Aid Board as the case progresses.

Legal aid in this case was originally granted way back in 1992 for proposed litigation in relation to claims that encephalitis, which is an inflammatory disease of the membrane surrounding the brain and spinal cord caused by an infection, was being caused by the MMR vaccine, and a group of parents sought to bring this litigation against a number of the drug companies who produced the vaccine. Later, at the time with which we are concerned, 1996, the legal aid was extended within that litigation to investigate claims following the MR vaccination programme, that was the Operation Safeguard vaccination programme in respect of school-aged children five to fifteen.

Then the issues broadened and the solicitors wanted to widen the litigation to cover other types of damage, and it is our case, as borne out by the documents that I am going to refer you to, that Dr Wakefield was very closely involved in advising in respect of the claimants in that litigation at least from February 1996, i.e. at the very least for two years prior to the publication of article. We know that from the newsletters which the solicitors acting for the claimants produced for their clients and for prospective clients, and the first in time that we have was dated 1 February 1996, and was sent to a parent to whom I have referred before, the parent of Child 12, Mrs 12. She is going to be giving evidence later, and also you are going to be hearing about the circumstances of her child, who was one of the children written up in article.

That newsletter is in bundle 1 of your chronological documents at page 90, and you will see at the top that it says “Dawbarns Solicitors” and it is in fact newsletter number 4, although, as I say, it is the first that we have in time. It deals, as you will see, with the progress of the litigation, and that is not a matter which particularly concerns us, and of course I should make it clear that it is hardly Dr Wakefield’s responsibility what the solicitors say about the litigation in the course of newsletters to their clients, but why we want to refer to it is because if you turn on to page 91 you will see, under the column “Other activities” on the left hand side:

“During the year we have had meetings and/or dealings with a large number of different people and organisation over the vaccine issues. Highlights are as follows”.

If you go down to the bottom of that column you see the heading “Dr Andrew Wakefield”:

“As you may have read in the Sunday Times of 17 December 1995 Dr Andrew Wakefield has published some very disturbing material which indicates a clear link between the measles element of the vaccine and Crohn’s disease (a persistent inflammatory illness of the digestive system). He has deeply depressing views about the effects of vaccines on the nation’s children. He is also anxious to arrange for tests to be carried out on any children vaccinated with the MR or MMR vaccine who are showing symptoms of possible Crohn’s disease. The following are signs to look for if your child has suffered some or all of these symptoms could you please contact us and it may be appropriate to put you in touch with Dr Wakefield.”

Then it sets out a series of symptoms:

“Failure to thrive
Loss of weight
Intermittent bouts of diarrhoea and/or stomach pain
Blood in faeces
Anal polyps and skin tags
Unexplained low level fever
Mouth ulcers
Aching joints”.

It then goes on, and you need not worry about the rest of the newsletter, referring to other experts from whom advice had been sought.

A couple of months after that newsletter, in May 1996, Mr Barr, the claimants’ solicitor, wrote to the lawyer at the Legal Aid Board who was then dealing with the case, Mrs Simpson, and that letter was dated 21 May, and it is in the same bundle that you have open before you at page 101. Again, that is a letter, remember, from the lawyer to the lawyer at the Legal Aid Board, discussing the whole progress of the litigation, and again it is not relevant to the matters that you have to consider, unless anyone suggests to you that he wants to read it, but I am going down to the third paragraph down:

“There does at last seem to be an increasing acknowledgement among the medical profession that these vaccines actually are causing damage. Dr Andrew Wakefield (who has been mentioned to you in Counsel’s Opinion and by me several times) is actually quite astonished at the evidence that he is uncovering and feels that objective tests may well establish conclusively that the measles vaccine is causing a wide range of these injuries.

I am waiting for his protocol proposals but a significant part of the costing will be in a proposal for testing a selected number of children to try to establish the link. I should emphasise that the hope is that the tests will be so positive that they will actually find the measles vaccine virus (as opposed to the wild type) in the areas of inflammation in the children. If that can be done it must be rather like catching a burglar red handed!

We do really want to keep going with our researches.”

Then Mr Barr refers to the fact that he has been dogged by delay, you may think like every lawyer complains all over the world, and he says, at the end of that paragraph:

“There are experts that we would like to continue to correspond with ….. in this country and in the USA ….. We have already had several constructive meetings with Dr Wakefield but there are other experts that we would like to involve covering a variety of different fields.”

The remainder of that letter you need not be concerned with.

The next document, which is an essential one, is dated 6 June 1996, and it is the next page on, page 103. That is a letter again from Mr Barr to Mrs Simpson, the Legal Services Commission lawyer, and you will see the second paragraph, which is the only one which we need be concerned with:

“To give you further information on the costing proposals I enclose a copy of a draft (not entirely finished yet) of Dr Wakefield’s proposed protocol for the study and his costing proposals.”

Attached to that letter were two documents. The first is on the next page 104:

“Proposed clinical and scientific study

A new syndrome: disintegrative disorder and enteritis following measles and measles/rubella vaccination

Coordinating investigator

Dr Wakefield”

It sets out the work that Dr Wakefield envisaged carrying out and for which he was seeking funding. It may seem familiar to you, and that is because it is almost, although not exactly, identical to the document attached to the Ethics Committee application form. You will remember I took you to a scientific protocol document attached to the Ethics Committee application form, and you will recall that that was submitted to the Ethics Committee some three months later in the September. I am not going to go through it again, but if you flip through it you will see the similarities, and at some point we will be looking at the detail of it more carefully, but if you go to the next page 105 you see the “Investigators - Department of Paediatric Gastroenterology - Professor Walker-Smith [and] Dr Murch”; “Responsibilities – Referral and coordination of patient admission for investigation. Clinical evaluation, procurement of blood, urine and serum samples. Colonoscopy, and tissue procurement”, and then it refers to the Department of Histopathology. If you go on to the bottom of the next page, 106, “Department of Child Psychiatry Dr Mark Berelowitz”, and 107 “Department of Neurology Dr Harvey”. So the same people involved. “Introduction” in almost identical terms on page 108 to that submitted to the Ethics Committee. A definition of disintegrative disorder or Heller’s disease again in almost identical terms. The scientific investigations which are envisaged and described in great detail are almost identical. If you go on to page 115, “Practical issues”, this is identical to the paragraph that I read out to you yesterday in relation to the scientific protocol – first, and significantly, a demanding protocol for the children and for the clinicians carrying out the procedures; due consideration and the details set out. Then you will remember there were the scientific references in the middle.

The nature of the investigations is also the same. Accompanying that proposal for a scientific study was a detailed costing proposal and that is at page 121, so it follows immediately afterwards, and you will remember that Mr Barr refers to this as Dr Wakefield’s costing proposal. It is headed:

“PROPOSED PROTOCOL AND COSTING PROPOSALS FOR TESTING A SELECTED NUMBER OF MR AND MMR VACCINATED CHILDREN

A protocol giving the detailed technical specification is attached”,

and that I have just referred you to.

“Objective

The objective is to seek evidence which will be acceptable in a court of law of the causative connection between either the mumps, measles and rubella vaccine or the measles/rubella vaccine and certain conditions which have been reported with considerable frequency by families of children who are seeking compensation.

It is hoped that using the testing protocol attached it will be possible to establish the causal link between the administration of the vaccines and the conditions outlined in this proposed protocol and costing proposal. The standard of proof aimed for will be at least the balance of probabilities but it is hoped that in many respects the level of proof will reach certainty or near certainty.

Briefly these conditions consist of: Crohn’s disease (and inflammatory bowel disease); there are also persistent reports of children suffering from symptoms akin to autism (here described as disintegrative disorder) coupled with inflammatory bowel disease.”

So that objective set out in the language of litigation – not surprising, of course, because this is a proposal to the Legal Aid Board – we say is highly relevant to the issue which I am going to be looking at in more detail later, namely the conflict of interest which existed between Dr Wakefield’s role in the litigation and his research project in 17296.

If you go on you will see the costings, the setting up costs for two groups:

“… a common one-off setting up cost in the sum of £26,5000 to cover the cost of use of laboratory equipment, laboratory staff and testing materials. It is anticipated that this sum will need to be paid once only even if the trial lasts for more than a year.”

Then there are two categories envisaged. The first is the category of inflammatory bowel disease, which is at paragraph 2. That is not part of project 17296 because that relates to children simply with inflammatory bowel disease and not also with a behavioural condition. It is the second category at paragraph 3 which we say is part of project 17296 and you will see it says

“Enteritis/disintegrative disorder cases”,

so this is bowel and behavioural.

“In contrast with the IBD cases, which have a prima face gastrointestinal pathology, children with enteritis/disintegrative disorder form part of a new syndrome. Nonetheless the evidence is undeniably in favour of a specific vaccine induced pathology. Many more tests have to be carried out for investigating these conditions and accordingly the costs of investigation are considerably higher.

The children will come into the Paediatric Gastroenterology Ward under the care of Professor John Walker-Smith. Costs for four nights say for the children and their parent plus colonoscopy will be £1,750.

The magnetic resonance imaging [the MRIs] evoked potential studies”,

and those are the other neurological tests I referred to yesterday,

“will cost £1,000 and the combination of the molecular, immunohistochemical, vitamin B12 and complement studies will cost a further £1,000.

The medical reports, which will be the compilation of reports from the individual experts in each of the disciplines, including Dr. Harvey, Dr Berelowictz, Professor Walker-Smith and Dr. Dhillon, Dr. Linnell, Dr. Law and Dr. Andrew Wakefield will cost £1,400. The total cost per child will therefore be £5,150.

The costings are based on a proposal that in each category five children should be tested making up a total as follows.”

Then we have got the setting up costs again, the first category, with which we are not concerned, and the second category, with which we are concerned, £25,750, and an estimated total of £57,750. Just to complete it:

“Note – should more children be tested under the protocol within the first year the set-up charge will not increase but will remain fixed. For each additional child in the first category the sum of £1,100 is to be added and for each additional child in the second category the sum of £5,150 will be added.

Conclusion

It is not of course possible to anticipate the conclusions that will be reached but the indicators are that it should be possible to establish a clear causative link between the vaccines and the two sets of conditions mentioned above.”

You will notice that the second category, which we say is part of project 17296, refers to five children and of course the entire project 17296 was an application in respect of 25 and included the 12 who were written up in article. So that is why we say that the Legal Aid Board proposal is part of project 17296.

The Legal Aid Board, on the basis of that costing proposal, agreed to fund the study and on 22 August 1996 the original legal aid contract was specifically amended so that, among other matters, Dr Wakefield could proceed with his proposals. If you go on to page 183 you will see that this is a standard Legal Aid Board Authority to do Contract Work, and as I have said, it is to the solicitors of course, not to any individual. It sets out what it is for and the relevant paragraph for our purposes is paragraph 2:

“To facilitate the setting up of the clinical and scientific study proposed by Dr. A.J. Wakefield in respect of 10 assisted persons at a maximum cost of £55,000 and to cover the work necessary by the solicitors in so doing at a maximum cost of …”,

and that is blanked out. I should say that there are redactions on this document which were put on by the Legal Services Commission because the relate to the costings to the lawyers rather than those that are relevant to this case.

The next day after that, Mr Barr, the solicitor, sent Dr Wakefield a letter, which is dated 23 August 1996 and it is at page 185.

THE CHAIRMAN: I am sorry to interrupt, at least in my bundle after 184 there is 187, so a couple of pages are missing. I do not know whether it is the same with the other Panellists as well. I think it seems to be the same.

MS SMITH: Are all the Panel bundles in the same position?

THE CHAIRMAN: Yes, I think it seems like it.

MS SMITH: I think in that case, I am very sorry to interrupt the flow of things, but I wonder if I could ask you to rise just for five minutes?

THE CHAIRMAN: I think, rather than wasting time, would it be possible that we could actually use this as our mid-morning break for 20 minutes, and we will resume at 11 o’clock?

MS SMITH: Of course.

THE CHAIRMAN: It will help in sorting this out and will avoid us interrupting you in your full flow again.

MS SMITH: Thank you very much, sir.

THE CHAIRMAN: We shall now adjourn and resume at 11 o’clock.

(The Panel adjourned for a short time)

THE CHAIRMAN: Ms Smith?

MS SMITH: Thank you very much, sir. We have sorted that out. There is an omission from your bundles and Miss Emerson is going to give you copies of the letter that I was about to refer to. Could I ask you to pop it back in at pages 185 and 186? (Same handed)

If I can just read through it, this is a letter to Dr Wakefield from Mr Barr, the solicitor for the claimants:

“Dear Andy

I refer to the telephone message left … and I am writing to confirm that at long last the Legal Aid Board has now given authorisation for the pilot study. The limit is £55,00 which does include the setting up costs.

I think we need to have a meeting about the mechanics of running the study because obviously we both have different roles to play and we also need to make sure that the investigation is as effective as possible both from your point of view and ours.

As I mentioned on the telephone the only slight cloud is that the Legal Aid Board rather hoped that within the £55,000 you would be able to include preparing us a written over-view in relation to vaccine damage. We have discussed this and I don’t know whether it is impertinent to suggest that you should do it within that funding bracket.

We also need to make sure that cases are properly selected for the pilot study. Obviously only legally aided children can be included (we have details of cases where legal aid has either not been granted or has not been applied for). Again a meeting might help to sort those out. For all the cases that we have obtained legal aid we have already put in hand obtaining records. In many cases we already have the complete set.

I assume that for the purposes of the pilot study you would like us to supply a full set of medical records and as much information about the cases as you can get hold of.”

Then there is reference to two of the vaccine support groups who were concerned about a forthcoming MMR campaign, and:

“When we meet I would like to discuss with you and perhaps engage in further correspondence with Dr Salisbury/The Committee on Safety of Medicines”,

and it then goes into some details and requests information about the vaccine trials.

That letter is followed on in terms of tracing the story through. That is in August 1996 and in September 1996 Dr Wakefield is referred to in another of the newsletters that I have already gone to, again produced by the solicitors in the MMR litigation and again sent to Mrs 12. That is at page 189.

THE CHAIRMAN: I am sorry, Ms Smith, I am actually just going to mention something. It is this letter of 23 August 1996 from Dawbarns Solicitors to Dr Wakefield. I think there is a reference to the Committee on Safety of Medicines in that letter in the last paragraph, and indeed page 186.

MS SMITH: Yes.

THE CHAIRMAN: Actually at that particular time I was a member of the Committee on Safety of Medicines from 1996 to 1999, but I have never seen this letter, I have had no dealing with it, but since I have read this Committee’s name I am just making it clear.

MS SMITH: Thank you very much for giving us that indication, sir. I do not know whether anybody wants to consider it or whether you would simply like me to proceed.

THE CHAIRMAN: Mr Coonan, I think you are probably the most relevant person to ask for your views.

MR COONAN: Sir, I did not know about that and I do not think I want to say anything about it at the moment. I would like just to consider what you have mentioned. Thank you very much for that.

THE CHAIRMAN: As I said, it is the first time I have seen this letter, the first time I have heard that the Committee on Safety of Medicines was ever involved. It may be that the Secretariat was involved, or the Chairman of the Committee on Safety of Medicines might have been involved, who was Professor Sir Michael Rawlings at that time; but I have got no other idea at all.

MS SMITH: Thank you very much, sir. Thank you for that information.

Then perhaps I can turn on to the September newsletter, which is at page 189. As I have told you, this was also sent to Mrs Twelve:

“MMR and MR vaccination cases”,

and it is dated September 1996, and if you go straight down to “Progress report”:

“Things have been a little quiet with the vaccine cases because we have been waiting for the go ahead from the Legal aid Board to progress the cases. We put in our request for extended funding back in May. This has just been authorised, and a further £135,000 of funding”,

and that is a reference of course to the funding which was for the lawyers, but we say included, as you will see, the money that I have been telling you about:

“…a further £135,000 of funding has been recently approved for the generic cases. This will enable us to set up and carry out a pilot study (see below), and will also enable us to carry out much more detailed work researching the vaccine cases.”

Then they refer to counsel’s opinion in the case and then they go on to a heading:

“Autism and inflammatory bowel disease

A substantial number of children referred to us are suffering from chronic stomach problems and/or have developed autism-like symptoms. Our own researches indicate that these two conditions may well have been caused by the MMR/MR vaccines and that they may well be linked.

We are trying to put together as much information as possible about the apparent link between these two conditions and the vaccines. If you have any information, or know of other families with children who have one or other of these conditions (or both) following vaccination we would be very interested to hear from you. If your child has the condition(s) and you have not yet received the fact sheet produced by Dr Andrew Wakefield, do contact us.”

Then there is a heading, “Pilot study”:

“If we can prove a clear link between the vaccines and autism/inflammatory bowel disease this will be exceedingly useful not only for cases involving those conditions, but also for other types of damage such as epilepsy.

To obtain the evidence to do this, we will be running a pilot study. Around 10 children with symptoms which are closely linked to the vaccine will be extensively tested by a team of doctors headed by Dr Wakefield at the Royal Free Hospital in London.

We will be selecting children to take part in the study from details and medical notes we already have. The investigations will involve a whole battery of tests, to be carried out by a number of leading experts in their fields. We will of course be liaising closely with the families concerned; and the doctors will be giving very full details of what will be involved.”

We do not need to read any more in that letter, except to remember that that description is in September 1996 and you will remember that it was indeed in September 1996 that the ethics committee application was submitted in respect of project 17296, in which it was stated that all investigations which were being undertaken on the children involved were clinically indicated and the method of funding was through ECRs (extra contractual referrals) i.e. NHS funding, and made no mention of Dr Wakefield’s involvement in the litigation or of any application for funding from the Legal Aid Board.

It is our case, as I have said, that the Legal Aid Board study was plainly the study which was submitted to the ethics committee and which ultimately became project 17296, and there was subsequent internal documentation at the Royal Free Hospital which amply confirms that. I am going to refer you to a few letters. I apologise for the fact that the evidence in this respect is a little bit bitty, in that the letter may have been written about something else, but its relevance to the point I am making is that we say everything slots together into a clear picture, that the Legal Aid Board study was part of project 17296. I am going to take you, as I say, to extracts from those letters and the first one is from Mr Else, the Chief Executive of the Trust. As I say, I hope you will bear with me because these will slot into place later when you hear the evidence.

This is a letter from Mr Else, the Chief Executive of the Trust, to Dr Wakefield on
4 September 1996 and it is at page 192, a couple of pages on. Those parts of the letter I want to refer are, first of all, the heading, “A New Syndrome”, so the same heading,

“Enteritis and disintegrative disorder following measles and measles/rubella vaccination.

I am writing to confirm that the Special Trustees will fund the salary of Ms Rosslyn Sim [a research worker at the time] to support the above project for a period of two years”.

Then this is the relevant part,

“I understand that children who would fall within the scope of the project are currently being seen at the Royal Free as part of the normal process for the delivery of health care and that tests, investigations and procedures that are clinically indicated are being undertaken. No tests, investigations or procedures will be undertaken that are not clinically indicated but which do form part of the research study protocol, until approval for the study has been received from the Ethical Practices Sub-Committee. The Special Trustees will wish to see evidence of this approval within the very near future”.

You will remember when I was opening to you yesterday, that I made the point that ethical approval underpins every aspect of a research study, including the funding, and here is the Chief Executive making that very point; that the whole process was reliant on that approval.

That letter plainly concerns the research project which became Project 172-96. That is clear from the title that is set out, which is identical; secondly, it is clear that Ms Sim, who was the research worker who was to be working on that study, that the Special Trustees agreed to fund her salary in relation to it.

The next letter is Dr Wakefield to the Dean, Professor Zuckerman, on 24 March 1997, which you will find in your next bundle, Bundle 2, at page 401. I am coming back to this letter later, which is why I am not reading the whole of it. Part of it deals with the conflict of interest point and, as I say, I am going to revert to that later on but for present purposes I am looking at it because it is relevant to the link between the Legal Aid Board study and Project 172-96, and that in the first sentences. “Dear Arie”, that is Professor Zuckerman,

“Further to our exchanges regarding the investigation of children with enterocolitis and autism, and especially the involvement of Dawbarns Solicitors and the Legal Aid Board, please find enclosed all documentation relating to this matter. This includes a letter to Dawbarns from the Legal Aid Board specifying the conditions for making the award. These conditions were based upon the enclosed protocol which has been approved by the Ethics Committee of the Royal Free Hospital”.

As I say, the rest of that letter may be highly relevant to other issues – I certainly do not want to be unfair to Dr Wakefield, but I will come back to it. Unfortunately the protocol enclosed with that letter is no longer attached, but what we say is that Dr Wakefield makes it clear in that letter that the protocol provided to the Legal Aid Board, on the basis of which the Legal Aid Board granted the funding, had been approved by the Ethics Committee, and we say that can only be a reference to Project 172-96. The reason we say that is that there is no other protocol which had been approved by the Ethics Committee regarding children with enterocolitis and autism, apart from Project 172-96. So that is the relevance of that letter.

It is also apparent, this same point, from another letter from Dr Wakefield, this time to Mr Phipps who is the director of finance at the trust, dated 23 May 1997. That you will find at page 471,

“Dear Mr Phipps, My group, the Inflammatory Bowed Disease Study Group, is currently involved in the investigation of a cohort of children with regressive autism and inflammatory bowel disease. The study is being undertaken in collaboration with Professor John Walker-Smith in the Department of Paediatric Gastroenterology. The study has provided some ground-breaking insights into the mechanisms of autistic spectrum disorders, and in particular the role of intestinal inflammation in this condition.

Children for this investigation have been recruited as ECRs from all over the country, and indeed, as private patients from the United States of America. In order to initiate the study, Martine Else [the Chief Executive] and the Special Trustees of the Royal Free Hampstead NHS Trust were kind enough to set up an account to fund Ms Rosalind Sim as the technician to process the samples taken from children”.

There is a reference back to Ms Sim, the researcher.

“This has proved to be most successful and will continue to be a major source of revenue for the Trust itself”.

Then these significant words,

“In addition, we have been awarded a grant of some £50,000 by the Legal Aid Board to investigate the possible association of this syndrome with the MMR vaccine. This money has been provided through Dawbarns Solicitors (see enclosed documentation) for the express purpose of performing the study outlined in the enclosed protocol. This protocol, as you will see, has been approved and passed by the Ethics Committee of the Trust. The cheque for the first instalment of this grant was initially paid into the Medical School, but queries have been raised by the Dean” –

I will revert to that in a minute –

“since this source of funding has never been obtained before. I have discussed with both Professor Pounder and Cenghisz Tarhan and we are agreed that the money would be more appropriately located in the account currently held to pay for Ms Sim”.

As I say, I will revert to other parts of that letter later. I should however finish reading the letter,

“I should add that the conduct of this study and the discoveries we have made have elevated the Royal Free Hospital to great heights in the world of autism research. The clinical profile that it has provided has greatly benefited the trust. We are receiving referrals on a daily basis and the funding provided by the Trustees will continue to help us investigate these patients appropriately. The study itself, although commissioned by the Legal Aid Board, seeks only to establish the validity of the parents’ claims of an association with MMR or not, and not to provide a specific answer, that is that vaccine was the cause. This is the condition upon which we undertook to do the study and the Legal Aid Board have agreed to it. I would be very grateful if you could indicate your willingness to receive these funds”.

That is the whole letter, but the purpose of it, for our purposes, is again that Dr Wakefield is stating that the Legal Aid Board money had been provided for the express purpose of performing the study outlined in a protocol approved by the Ethics Committee. Again, we say that that can be no other project than Project 172-96.

The last letter I am going to refer you to is page 493. Again, the first paragraph relates to concerns which have been raised about conflicts of interest, and I will return to that issue later on. You will see that that letter says,

“I am writing to confirm that there is no conflict of interest in relation to the Legal Aid funding for our clinical study of children with autism and intestinal inflammation.

This study, which has been sponsored by the Legal Aid Board, is similar to a study they have sponsored”,

and then it goes into another study, an investigation into the Gulf War Syndrome.

“Please find enclosed a copy of our first paper submitted to the Lancet concerning the children under investigation. This has been an extremely successful study and has clearly demonstrated a new pathology in these children and put the Royal Free Hospital as the world leader in this field. We are aware of 300 children who merit investigation under this protocol, most of these as ECRs (or commissioned referrals for the future)”.

So again, for present purposes, the significance of this letter lies in Dr Wakefield’s acknowledgement to Mr Else that the Legal Aid Board funding was for the clinical study of children with autism and intestinal inflammation. He goes on and provides the further link that a copy of the paper relating to that project had been submitted to the Lancet concerning the children under investigation and the ultimate publication of the study in The Lancet is another important aspect of the case which I will be going on to.

What we say, as I say, about what I apologise for being rather bitty documentation, is that it underlines a point which may be very important when you hear the defence; that is, that the Legal Aid Board and Project 172-96 are inextricably linked with each other. I am now going to resume the chronology in relation to the litigation going back to September 1996 when Dr Wakefield wrote to Mr Barr, the claimant’s solicitor. I am sorry to take you backwards, but that is in Bundle 1 at page 237. This is a letter from Dr Wakefield to Mr Barr at Dawbarns:

“Dear Mr Barr, we are now in a position to start work on this study on behalf of affected children identified by yourselves and approved by the Legal Aid Board. I would be grateful if the initial sum of £25,000 could be transferred to the Royal Free Hospital School of Medicine for the purposes of initiating and carrying out the initial phase of this analysis. I will write to you once again when the remainder of the funding is required. Naturally we will keep you appraised of progress and let you have the results and the reports as soon as they are complete”.

We say that letter is highly significant because the reason Dr Wakefield says he is now in a position to start work and requested his Legal Aid Board funding, was because he anticipated that Project 172-96 would shortly receive Ethics Committee approval. The request was for the first £25,000 in relation to the project which I referred you to in the costing proposal, with the remainder to follow when required. Mr Barr accordingly wrote to a Mrs Cowie, who was by then the Legal Aid Board lawyer dealing with the matter on 23 October 1996. If you go on to page 268, various matters relating to the conduct of the litigation are to be found in the first paragraph. Then third paragraph from the bottom,

“Dr Wakefield is about ready to get up and running with his testing of the clients and I enclose a copy of his preliminary account to cover the setting up charges.

I also enclose a CLA28” –

I hope no one is going to ask me what that is because I do not know; it is obviously some document that has to pass between the solicitor and the Legal Aid Board –

“and I should be grateful if you would arrange for £25,000 to be issued to us so that we can pass it on to him. In view of the substantial size of this sum is there any additional documentation that the Legal Aid Board would like before the money is released to the Royal Free? We have of course already emphasised to him” –

I referred you to that letter –

“that the work must be done in accordance with the pilot study already submitted to you”.

On 4 November 1996, payment of the money by the Legal Aid Board was duly authorised. A couple of weeks later, on 22 November 1996, Mr Barr wrote again to Mrs Cowie, the Legal Aid Board lawyer, and that is at page 317:

“Dear Mrs Cowie, thank you for your letter of the 4 November 1996 and for so promptly authorising the payment to the Royal Free. You might be interested to know that they have already started testing some of the children and so far every single child tested has come out positive with positive staining for measles virus in the inflamed areas. They will now need to do very much more detailed testing to confirm that it is the measles vaccine virus that is causing the damage. This, of course, is being put in hand”.

Then he refers to a couple of matters he wants to raise,

“1. When we talked on the telephone we discussed obtaining the preliminary report from Dr Andrew Wakefield but I did not specifically put any figure in for Dr Wakefield’s fee personally. I had understood, wrongly it turns out, that his fee would be included in the figure of £55,000. It now turns out that that is not actually correct and that he does require a separate fee for preparing his preliminary report”.

Then he asks for an extra provision to be made in relation to that. Secondly,

“We have seen an absolute explosion in the number of autism cases. Autism claims are far and away the greatest number of cases now and it is very important to try to establish a level of proof that the autism is connected with the vaccine. Dr Wakefield has suggested that one way of producing quite convincing evidence is to do a survey of the autism cases. At the time of dictating this letter 170 cases have been referred to us (either directly or through JABS) –

a pressure group in relation to a vaccination –

“This represents nearly 50 per cent of all MMR cases. Those that we have already investigated show a very similar pattern of children developing normally right up until the time that they are vaccinated”.

He then sets out a number of matters at some length which are not of any great relevance until we get down to the bottom of the page, the penultimate paragraph,

“I would like to try and establish that there is a fairly consistent time link between the administration of the vaccine (MMR) and the onset of autistic features. To achieve this we have prepared a survey questionnaire (enclosed). This has been approved by Dr Wakefield. The aim is to send it out to all 170 families who are now on our database and invite them to fill it in as accurately as they can.

We would then collate the data and in particular would be looking very closely at the date of onset of the beginning of the autistic condition”.

Then he sets out the costings in relation to that, which we need not trouble with. Mr Thomas is drawing my attention, if I can turn back a page to one paragraph I did not read and should have done, simply because it draws the distinction which we say was a very real one between MR and MMR. It is in the middle of the page. You will see,

“We have a small number of measles cases, about 12 in all, none of which involve autism. One would have expected at least two or three”.

Then the paragraph,

“It very much appears that autism is associated with the triple MMR vaccine. It is not showing up at all in any of our MR cases, although the reason may be that children vaccinated with that vaccine are older”.

Then going down to the bottom of page 318, which was the last paragraph I read to you,

“We would then collate the data and in particular we would be looking very closely at the date of onset of the beginning of the autistic condition. Mostly this appears as children becoming withdrawn, losing speech, losing co-ordination etc. The onset seems to be approximately between two and six months after the vaccination but that is not hard and fast. We have one or two cases where it took quite a lot longer than that. Dr Wakefield feels that if we can show a clear time link between the vaccination and the onset of symptoms, we should be able to dispose of the suggestion that it is simply a chance encounter. The reason for this is that there is quite a wide range of ages between which the vaccine is administered. If we can show that the onset of the autism is related in time to the vaccine, we should be able to establish the point that it is no coincidence that children become autistic after the vaccination. To set up and send out this survey will involve some additional costs”.

He sets out those costs and he says, after having set them out,

“After that analysis and collation of the report by [his assistant and himself] plus discussions with Dr Wakefield (along with his fee for examining the date” – i.e. the data arising from the questionnaire – “and possibly writing up the report himself) …”

Then he gives further figures.

We rely on that letter in relation to our contention that there was an extremely close nature of Dr Wakefield’s involvement in the litigation at that time, and that is highly relevant to the issue of the potential conflict of interest which we say existed.

Going on with the payment of the money: on 6 December 1996, Mr Barr wrote to Dr Wakefield enclosing the cheque for £25,000, and the cheque is at the top of page 338A.

At page 337 you will see the letter which was sent from Mr Barr with that cheque:

“Dear Andrew,

Further to our discussion on Thursday, I enclose a cheque for £25,000 made out to the [Royal Free Hospital School of Medicine] in respect of the setting up costs and first year’s costs of the MMR investigation. I shall be grateful if you could arrange to let me have an official receipt and also for the enclosed receipt to be signed.

This funding has been provided directly by the Legal Aid Board and the payment should go exclusively for the furtherance of investigation in to the side effects of the MMR/MR vaccine.

It is also subject to the conditions set out in my letter to you of 14 October 1996.

The findings you and your colleagues are making sound extremely impressive and I certainly have to say from our point of view that we are delighted with the help that you and the rest of your team at the Royal free are giving us in investigating these tragic cases. I believe it is a unique exercise that we are carrying out and I for one am certain that the MMR vaccine has a lot to answer for”.

Then they propose a meeting with the entire team, which, I should say, as far as we are aware, did take place.

When that money arrived with Dr Wakefield, as you may have picked up in one of the letters that I referred you to earlier, initially an attempt was made to pay it into the medical school’s accounts but the dean, Professor Zuckerman, had already raised concerns when he had heard about this source of funding, and particularly concerns as to whether it gave rise to a conflict of interest. That had resulted in his taking the initiative to take advice from the legal and ethics divisions of the British Medical Association and raising the matter with the chief executive of the NHS Trust of the Royal Free Hospital and with Dr Wakefield himself. That is how the correspondence which I referred to earlier comes into play, and I am going to look back at some of it. Bundle 2, page 393, first of all. This is a letter from Dr Wakefield and you will see from the contents that it obviously follows on from a telephone conversation that he had with his dean:

“Dear Arie,

Following our telephone conversation the other day, I agreed that I would look into the question of whether there was a Parliamentary Select Committee being convened on the subject of measles vaccine and Crohn’s disease, and specifically my link with the solicitors, Dawbarns, in this matter. Dawbarns are not aware of any such developments and claim not to have misquoted me at any stage …”

This is obviously a reference to some other matter concerned with this issue:

“I can confirm that I have been unable to establish that any Parliamentary Select Committee or other committee has been set up to examine this …”

But he then goes on to the matter which is directly relevant:

“You mentioned a conflict of interest when we spoke. This is something which has exercised my mind greatly in the interim. I feel I must go on record as stating that I do not see how any conflict of interest exists. It is, as I am sure you will agree, our joint and several responsibility as members of the medical profession to use our training and expertise appropriately. In the context of the current measles vaccine safety/consequences debate, I am providing independent expert guidance based on facts available to me. I do this in common with colleagues worldwide. The fair legal assessment of potential claims relies on high-calibre expert advice. The GMC and the Royal Colleges have long accepted this premise.

In the particular circumstances with which I am dealing, there is, I believe, an even higher moral obligation to act as an expert adviser. We are faced with a situation where the most vulnerable category of patients, i.e. children, may be put at risk. It is right and proper therefore to review the facts, assess them, and offer guidance.

I hope these comments are helpful. Please do feel free to contact me if you wish to discuss my role further.”

Professor Zuckerman was unimpressed by this explanation, and you can see that from the letter that he sent in response, which is at page 397:

“Dear Andy,

Thank you for your letter of 10th March 1997. There appear to be two misunderstandings.”

The first one relates to the Parliamentary Select Committee and is, as I say, irrelevant to the matters we are considering. The second says:

“I do not think that there is any conflict between duty of care to patients or the provision of independent expert advice to lawyers. However, it is a different matter when lawyers fund a particular piece of research where a specific action is contemplated. This surely suggests that some preliminary legal discussions have take place, and that a specific action is contemplated. If so, then the interpretation must surely be that a conflict of interest may well exist. The School must, therefore, seek expert advice, but in the meantime you should know of my concern.”

The letter that follows on from that is the one that I referred you to before and told you that I would revert to, which is at page 401. I am going to read it again. I did not read the second half of it, I only read the first half but I will read it in its totality so that it makes sense now:

“Dear Arie,

Further to our exchanges regarding the investigation of children with enterocolitis and autism, and especially the involvement of Dawbarns Solicitors and the Legal Aid Board, please find enclosed all documentation relating to this matter. This includes a letter to Dawbarns from the Legal Aid Board specifying the conditions for making the award. These conditions were based upon the enclosed protocol which has been approved by the Ethics Committee of the Royal Free Hospital. I got the impression from Roy”

- I think that is a reference to Professor Roy Pounder who was the head of Dr Wakefield’s department –

“that you were concerned that we were being contracted to provide a specific answer” -

that is that measles vaccine or the MMR vaccine was the cause of this disease –

“- that is absolutely not the case. We are being funded to conduct a piece of scientific research to establish or refute the link between MMR vaccine and the disease. There are absolutely no preconditions concerning the outcome. If this were the case, you may rest assured I would never have been involved in the first instance. The science must lead and everything else follows. As with medical experts’ opinion elsewhere, I am being asked to provide my opinion, whether that opinion is positive or negative. It is on this basis, and only on this basis, that I have agreed to assist in this matter. I hope that this issue can be resolved as quickly as possible and my group are working to achieve this end.”

That letter you will note has a handwritten note on the top of it and of course it does not address the issue that Professor Zuckerman had raised, namely that the research involved Legal Aid Board funding. The note at the top says:

“Please copy to Mr Blatch. This document confirms my worst fears”.

You will be hearing from Professor Zuckerman that he wrote that note on it and that the concerns that he was referring to were concerns about the conflict of interest which he was concerned might arise.

As a result of the advice that Professor Zuckerman got from the British Medical Associated he contacted Dr Pegg as chairman of the ethics committee to explore with him whether the committee had investigated or considered this very issue, namely whether it was an appropriate involvement of Legal Aid Board money with a piece of medical research. Dr Pegg simply responded by saying that he was completely unable to assist because he had no knowledge of any project involving funding from the Legal Aid Board. That is where the situation remained as far as the medical school was concerned. Professor Zuckerman refused to accept the money, and it was agreed that it would be transferred instead to an account held by the special trustees of the Royal Free Hospital. That is an account held to benefit research at the hospital which is quite separate from the medical school, and the special trustees account was for the purposes of Dr Wakefield’s research generally. Therefore, we say, and the significance of all this is, that Dr Wakefield was well aware from the outset as to the unusual nature of this funding and of the significant concerns in relation to conflicts of interest which had been raised at a high level within his own institution by the dean of the medical school.

To complete the story, the remainder of the money, in the form of a cheque for a further £25,000 – so there was £25,000 for the setting up costs and then a further £25,000 was received much later, in March 1999, when Dr Wakefield ultimately send his interim report to the Legal Aid Board.

As far as the story of the litigation is concerned, we do not need to go any further for the purposes of these proceedings, except that I should tell you for completeness that ultimately public funding was withdrawn from the litigation by the Legal Services Commission. I want to make it absolutely clear that that withdrawal by the Legal Services Commission had nothing to do with the charges which you are considering in respect of Dr Wakefield.

Turning on now to the money: what happened to the Legal Aid Board funds? As we have said, the answer to that is that the funds went into Dr Wakefield’s general research funds, and in particular into an account held in his name by the special trustees.

It is not possible to say what they were actually used for because there is now, owing to the lapse of time, a lack of financial records, but one thing we say is very clear, the amounts claimed for the investigation of the children, namely £1,750 per child for a four night stay for a child and parent at the Royal Free, plus colonoscopy under Professor Walker-Smith’s care, an MRI (magnetic resonance imaging) scan, and evoked potential studies, at £1,000 per child, and a combination of molecular immunohistochemical vitamin B12 and complement studies at a further £1,000 per child, which totals £13,750, was not needed, nor used, for those investigations.

As you have heard, it was the constant refrain of Dr Wakefield that the investigations being carried out on these children were part of their clinical care. They were clinically indicated tests, and that they were to be funded by the National Health Service through the extra-contractual referral scheme, ECRs.

You will recall that project 17296 was in respect of 25 children and the clear indication given that the tests were clinically indicated and would be funded by ECRs, certainly in respect of 10 of the children you will be considering their medical records or their GPs, and in some cases both, confirm that the funding for the referral was covered by the NHS, and it is our case that there is absolutely no reason to suppose that all the children in project 17296 were not also covered by NHS funding if the insurances were accepted that the tests were part of routine clinical care. So, thus, we say, the money granted by the Legal Aid Board for the investigations set out in very specific terms, four nights stay and the tests set out, in the costing proposal by Dr Wakefield for the Legal Aid Board, that money was not needed nor used for the purpose which Dr Wakefield claimed, and it is our case that that is dishonest and a misuse of public funds.

I am going to turn on to another inter-related subject. Before I do so I should say – I said this at the beginning of the section about the Legal Services Commission and the finances – you should bear in mind that those charges relate to Dr Wakefield alone, and I repeat that. There are no charges relating to those matters in respect of either of the other two doctors.

I am now going to turn on to the role that was played in relation to this whole matter in The Lancet. That arises because, ultimately, in February 1998 a paper appeared in The Lancet journal with the title “Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children”, and it dealt with 12 children, 11 of them, as I have said, you will be hearing about in detail. The twelfth was apparently a private patient from the United States of America, and the paper is in bundle 2 at page 783. I think this is probably one of the documents, like the ethics committee application, with which the Panel are going to become very familiar over the next few weeks, and I am not going to go through the whole of it but I am going to make a first attempt at familiarising you with those aspects of it which we say are relevant. First of all you will see the authors’ names are set out at the top, 13 co-authors, and they include Dr Wakefield, Professor Murch and at the end Professor Walker-Smith. I have read the title to you, that is the first time that you will have heard the phrase “ileal-lympoid-nodular hyperplasia”. Lymphoid-nodular hyperplasia is the term for large lymphoid follicles which cause protrusions of the mucosa, i.e. the surface, of the intestine. In these cases in particular it was found in the ileum of many of the children who were investigated. It is not a very clearly defined term and there is some issue between gastro-enterologists as the degree to which it is a normal variant. The resolution of that issue, which is bound to be alluded to, particularly by the experts, is not for this Panel. Suffice to say for these purposes, its presence and appearance in these cases was thought to be of significance by those involved in project 17296 and that is the reason why it was written up as it was in The Lancet article.

If we go briefly through the article, the summary, first of all, page 783:

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

Then you will see:

“Methods: 12 children (mean age 6 years …) were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain. Children underwent gastroenterological, neurological and development assessment and review of developmental records. Ileocolonoscopy and biopsy sampling … MRI … EEG and lumbar puncture were done under sedation. Barium follow-through radiography was done where possible. Biochemical, haematological, and immunological profiles were examined”.

Then:

“Findings Onset of behaviour symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 [cases], with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behaviour disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEF tests were normal.”

It then goes on to abnormal laboratory results, and concludes:

“Interpretation We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.”

If you go then on to:

“Introduction

We saw several children who, after a period of apparent normality, lost acquired skills, including communication. They all had gastrointestinal symptoms, including abdominal pain, diarrhoea, and bloating and, in some cases, food intolerance. We describe the clinical findings, and gastrointestinal features of these children.

12 children, consecutively referred to the department of paediatric gastroenterology with a history of a pervasive developmental disorder with loss of acquired skills and intestinal symptoms (diarrhoea, abdominal pain, bloating and food intolerance) were investigated. All children were admitted to the ward for 1 week, accompanied by their parents.”

Then we see:

“Clinical Investigations

We took histories, including details of immunisations and exposure to infectious diseases, and assessed the children. In 11 cases the history was obtained by the senior clinician” – that is Professor Walker-Smith – “Neurological and psychiatric assessments were done by consultant staff”,

and there is a reference to Dr Harvey and Dr Berelowitz (the neurologist and the psychiatrist) using the particular psychiatric criteria.

“Developmental histories included a review of prospective developmental records from parents, health visitors, and general practitioners. Four children did not undergo psychiatric assessment in hospital; all had been assessed professionally elsewhere, so these assessments were used as the basis for their behavioural diagnosis.”

Then it sets out how ileocolonoscopy was performed and how the procedure was recorded by video and still images, that it was done under sedation, and that also under sedation cerebral MRIs and EEGs were performed, and where compliance made these possible evoked potentials, that is other neurological tests, and lumbar punctures were done. Then the laboratory investigations are set out and I do not propose to go through those now.

On the next page, 784, you will see the express reference which identifies this paper as Project 172-96. On page 784:

“Ethical approval and consent

Investigations were approved by the Ethical Practices Committee of the Royal Free Hospital NHS Trust, and parents gave informed consent.”

Then on to the “Discussion”, which is page 785:

“We describe a pattern of colitis and ileal-lymphoid-nodular hyperplasia in children with developmental disorders. Intestinal and behavioural pathologies may have occurred together by chance, reflecting a selection bias in a self-referred group; however, the uniformity of the intestinal pathological changes and the fact that previous studies have found intestinal dysfunction in children with autistic-spectrum disorders, suggests that the connection is real and reflects a unique disease process.”

They then set out the history behind the hypothesis, and if you go on to page 786, the right hand column:

“Despite consistent gastrointestinal findings, behavioural changes in these children were more heterogeneous. In some cases the onset and course of behavioural regression was precipitous, with children losing all communication skills over a few weeks to months. This regression is consistent with a disintegrative psychosis (Heller’s disease), which typically occurs when normally developing children show striking behaviour changes and developmental regression, commonly in association with some loss of coordination and bowel or bladder function. Disintegrative psychosis is typically described as occurring in children after at least 2-3 years of apparently normal development.

Disintegrative psychosis is recognised as a sequel to measles encephalitis, although in most cases no cause is ever identified. Viral encephalitis can give rise to autistic disorders, particularly when it occurs early in life. Rubella virus is associated with autism and the combined measles, mumps, and rubella vaccine (rather than monovalent measles vaccine) has also been implicated.”

Then there is a reference to two papers, one by Fudenberg, noted that 15 of 20 autistic children, the first symptoms developed within a week of vaccination, and Gupta, who commented on a striking association between MMR vaccination and the onset of behavioural symptoms in children he had investigated for regressive autism. It goes on:

“Measles virus and measles vaccination have both been implicated as risk factors for Crohn’s disease and persistent measles vaccine-strain virus infection has been found in children with autoimmune hepatitis.”

I am trying to set those parts which I want to refer to fairly in context, it goes on:

“We did not prove an association between measles, mumps, and rubella vaccine and the syndrome described. Virological studies are underway that may help to resolve this issue.

If there is a causal link between measles, mumps, and rubella vaccine and this syndrome, a rising incident might be anticipated after the introduction of this vaccine in the UK in 1988. Published evidence is inadequate to show whether there is a change in incidence or a link with measles, mumps, and rubella vaccine. A genetic predisposition to autistic-spectrum disorders is suggested by over-representation in boys and a greater concordance ….. in ….. twins.”

It then goes on, and if I can take you to what it ultimately says at the bottom:

“We have identified a chronic enterocolitis in children that may be related to neuropsychiatric dysfunction. In most cases, onset of symptoms was after measles, mumps, and rubella immunisation. Further investigations are needed to examine this syndrome and its possible relation to this vaccine.”

Then there is:

“Addendum:

Up to Jan 28, a further 40 patients have been assessed; 39 with the syndrome.”

At the bottom I ask you to notice, under the acknowledgements, an acknowledgement in relation to funding, and again this is relevant to the charges that Dr Wakefield faces:

“This study was supported by the Special Trustees of Royal ….. Hampstead ….. Trust and the Children’s Medical Charity.”

Now, it is not part of the duties of any scientific journal editor, to which a paper is submitted, to investigate the facts behind it. Obviously, the authors are trusted to present their research honestly and accurately, and obviously they have a responsibility to do so. The central theme of this paper relates to the finding of lymphoid nodular hyperplasia in conjunction with developmental problems, but nevertheless it is clearly postulated that the possible environmental factor trigger for the children’s condition might be the MMR vaccine, and I underline again the last paragraph of the paper on page 787:

“We have identified a chronic enterocolitis ….. that may be related to neuropsychiatric dysfunction. In most cases, onset ….. was after measles, mumps, and rubella immunisation. Further investigations are needed to examine this syndrome and its possible relation to this vaccine.”

This paper was published with a commentary which was commissioned by Dr Horton, who was and is the editor of The Lancet, especially to be published with it in order to ensure that the paper was published responsibly, i.e. to underline the limits of the findings in the paper and to set out the global benefits of measles vaccination, and that commentary was printed in the same edition of The Lancet as the paper that I have just referred you to, and it is on the next page, page 788. I am not going to read you the whole of it, but I am going to take you briefly through it. It is under the heading “Vaccine adverse events: causal or coincidental?”, and, as I say, it was specifically commissioned as a commentary on The Lancet paper that I have just referred you to.

“Although immunisations rank among the most important public-health measures, no vaccine is perfectly safe ….. vaccines are given to millions of healthy people, usually infants, extremely high standards for vaccine safety are demanded. It is therefore important to examine, critically and with an open mind, the report by Andrew Wakefield and colleagues of several children whose chronic bowel and behavioural abnormalities were linked by their parents and physicians to measles, mumps, and rubella (MMR) vaccination.

An adverse event can be said to be caused by a vaccine (ie, a true reaction) if it is associated with a specific laboratory finding and a specific clinical syndrome or both. Alternatively, a clinical or epidemiological study is needed to find out whether the rate of a given syndrome in vaccinated individuals exceeds that expected among unvaccinated controls. Such studies require acquisition of data in an unbiased way. Because of the inherent methodological limitations of epidemiological studies” – that is population studies – “biological plausibility, consistency, strength, and specificity of association must also be considered in inferring causation. How well then do the features of the association reported by Wakefield and colleagues fit with causality?

….. hundreds of millions of people worldwide (including ….. Scandinavia and North America, where there are excellent clinical facilities) have received measles-containing vaccine without developing either chronic bowel or behavioural [disorders] since the mid-1960s. This finding provides important negative evidence as well as an appropriate framework for the assessment of the cases described by Wakefield and colleagues – namely, that if MMR ….. does cause this syndromes, it does so extremely rarely.

Is the syndrome reported today clinically unique? Ileal lymphoid hyperplasia is non-specific. Autism was known well before MMR vaccines became available. Are there unique laboratory features, including detection of vaccine viruses in clinical specimens where they would not be expected? Although Wakefield has reported the detection of these viruses in patients with ….. (IBD), other investigators, using more sensitive and specific assays, have not been able to [produce] these [results].”

Then it refers to the fact that there is indeed a negative report on that very issue, also published in The Lancet in that edition.

“There is no report of detection of vaccine viruses in the bowel, brain, or any other tissue of the patients in Wakefield’s series.

This leaves epidemiology as the other means of evaluating causation. Is there selection bias? The Wakefield report is based on cases referred to a group known to be [specifically] interested in studying the [relationship] of MMR vaccine with IBD, rather than a population-based study. A first dose of MMR vaccine is given to about 600,000 children every year in the UK, most during the second year of life, the time when autism first becomes manifest. Not surprisingly, therefore, some cases will follow MMR vaccination. Biased case-ascertainment, as in this study, will exaggerate the association.

Was there recall bias? It is usually difficult to date precisely the onset of a syndrome such as autism. Parents and others may attempt to relate its onset to an unusual event such as coincidental postvaccinal reaction. The clearest example of such an association was the link between infantile spasms and pertussis vaccines”.

That is a reference to the whooping cough vaccine.

“the vaccine tends to unmask rather than cause the syndrome.”

Then there follows on further analysis of the various issues which have to be thought about at least when The Lancet paper is being considered. At the bottom of the page:

“Effective and credible systems are needed for the detection of vaccine-associated adverse events through pharmacovigilance, for distinguishing causal reactions from coincidental reactions by pharmacoepidemiological or other studies, and for risk communication. Without such a system, vaccine-safety concerns such as that reported by Wakefield and colleagues may snowball into societal tragedies when the media and the public confuse association with causality and shun immunisation. This painful history was shared by the UK (among others) over pertussis in the 1970s after another similar case series was widely publicised, and it is likely to be repeated all too easily over MMR. This would be tragic because passion would then conquer reason and the facts again in the UK.”

So that was the commentary that was published with it, but those steps which were taken by The Lancet were done on the basis, as must exist in all scientific papers, that the study had been responsibly reported by its senior authors, and we say, and this charge relates only to Dr Wakefield and Professor Walker-Smith, that they had not reported it responsibly in a number of different respects which I am going to set out to you in a moment.

Before I do so, I have to diverge, as it am afraid is the way with this case, into a by-way, and examine with you a little further this issue of vaccination. The context in which this research was written up is a very important element in the charges in relation to Dr Wakefield and Professor Walker-Smith. These charges do not relate to Professor Murch because there is no evidence at all to suggest that he had any involvement in the circumstances of referral of the children involved. The paper, as you have heard, reported a temporal link made by the parents in respect of eight of the children between the onset of their child’s developmental regression and the MMR vaccination. It is our case that the reporting of that link was well known to both doctors to carry with it major implications for the health of the children in this country.

You are going to be hearing about that from the horse’s mouth in the figure of Professor Salisbury, who is the Director of Immunisation at the Department of Health, but I am just going to tell you in brief terms why this issue of vaccination is an important one. Back in 1986 children were, as I have already told you, receiving the single measles vaccine. The take-up rate for the vaccine historically was very low, only about 60 or 65 per cent of children were having it. There were measles epidemics in alternate years, and there were up to 20 deaths from measles in each epidemic.

Rubella, or German measles, as you know, is a mild illness for most children, and its real danger lies in another area, and that is its effects if it is caught by women in the first trimester of pregnancy, when, as you know, it can cause severe foetal deformity. For that reason, in the 1980s the vaccination strategy in relation to rubella was different from measles. There was selective immunisation of some prepubertal girls, and then there was later screening of women, so that those susceptible could be vaccinated after the birth of their child to protect them during their next pregnancy.

That strategy was not designed to protect children from catching rubella, and indeed most of them did catch it. Inevitably, some women were unprotected and cases of congenital rubella syndrome – in other words, children born with deformity – continued to occur.

In the US the strategy was to immunise with MMR, all three at once, and that was preventative, not only in relation to measles but also in relation to rubella. It is an effective strategy provided that the take-up rate is sufficiently high in young children to interrupt transmission between children. If it is not high enough to do that, then the average age of infection goes on advancing and the risk to pregnant women increases.

In the UK, by 1986 the measles coverage was rising and so a series of consultations was held and put before the JCVI, that is, the Joint Committee on Vaccination and Immunisation, which is the Statutory Committee which provides independent expert advice on immunisation to the Secretaries of State for Health of England, Wales, Scotland and Northern Ireland. Eventually, as a result of their considerations, in 1988 the JCVI recommended that the national programme should change from single measles, selective rubella and no mumps vaccination (which is what, as I have explained to you, it had been) to a single dose of MMR, measles, mumps and rubella, at 12 to15 months of age.

That programme had dramatic effects. Coverage increased, the incident of measles fell, hospital admissions for mumps/meningitis, which had been around 400 per annum, fell as well, hugely; rubella infections in pregnancy, and the knock on of that, which must not be forgotten, which was terminations as a result of that, nearly disappeared. Eventually, by 1998 the incidence of measles was at historic low levels so far as to be considered eliminated in the UK.

You will be hearing from Professor Salisbury as to the ---

MR COONAN: Dr Salisbury.

MS SMITH: My friend is making noises, which I cannot help hearing. Professor Salisbury in fact was awarded a chair very recently and he is Professor Salisbury. You will be hearing from Professor Salisbury as to all the complexities of the immunisation programme, but one thing is clear: in order to be successful, a very high percentage of coverage is absolutely essential. Thus, we say, anything which might shake public confidence in the vaccine risks a reduction in coverage, and therefore has major health implications.

It is our case that these two doctors cannot possibly have been unaware of those implications. Dr Wakefield had had frequent communications with the Department of Health in relation to his research from 1992 onwards. In 1997 both he and Professor Walker-Smith attended a meeting with the then Minister for Health and Professor Salisbury to discuss the implications of their research. Indeed, in the application to the ethics committee, if you will think back to what I was telling you yesterday, they acknowledge the very point that I am making, the seriousness of the matter, because when they are setting out their research hypothesis they say:

“Our ability to confirm or exclude a role of measles or measles/rubella also has major implications for public health.”

What is the relevance of all this to The Lancet publication? We say it is this: whether or not this temporal link between autism and MMR perceived by some parents should have been reported in this paper is not the issue in this hearing. The principle of scientific freedom of speech, as I said to you when I opened the case yesterday, is an important one, and it is one which the GMC should respect. But, we say, when the impact of a paper is as potentially far reaching as this one, then the authors have a very grave responsibility to ensure that the manner in which they write that paper is honest and accurate; that the patient population involved in it is honestly and accurately described; that all the information given in it and about it is likewise accurate and honest; that any circumstances relevant to the findings described are made absolutely clear; and that any interest which could give rise to a perception of a conflict of interest is disclosed to the journal to whom the paper is submitted.

You could, of course, say, and you would be right to say it, that those principles are applicable to any scientific paper, and there are thousands of papers published in thousands of journals all over the world, no doubt with varying degrees of accuracy in relation to their contents. But this paper and these two doctors’ responses to questions about it, we say, predictably had major public health implications and contained, we say, not minor inaccuracies, but glaringly misleading information, the misleading nature of which could not be known to anybody reading it except for the authors, Dr Wakefield and Professor Walker-Smith. Whilst, as I say, the GMC is not here to police scientific freedom of speech, one of its roles must be to ensure that doctors do not break the trust in their integrity which underpins the research that they report. We say in this instance these two doctors did abuse that trust and they did so in a context, as I have said, of particular seriousness.

The first of those which is set out in the charges under the heading “The Lancet Paper” is the failure to state the nature of a research project and the circumstances of referral. Firstly, nowhere in the paper is the true nature of the circumstances of how these children came to be investigated made clear. Nowhere, we say, is there a reference to the fact that 11 of these children were investigated as part of a study, the whole point of which had been to test the association of the vaccine with intestinal problems and behavioural disorders. On the contrary, they are described as consecutively referred with a history of pervasive developmental disorder and intestinal symptoms. We say that the clear message of that description to anyone reading The Lancet paper, be they a scientist or a journalist or an ordinary member of the public, is that these children followed a standard route of referral, ie one by the recognised route of a general practitioner or another consultant, who referred to the gastroenterology department because the child had gastrointestinal symptoms which needed looking at in a specialist referral unit in the ordinary course of that unit’s work.

You will ultimately hear in detail about the circumstances of referral of six of these children, that is, half of the group seen, and I am only going to summarise it for present purposes while I am talking about the way in which it was described.

Child 1,9, 5 and 10, were indeed referred to the gastroenterology department, but not because they had gastrointestinal symptoms. In Child 1 the referral letter has no mention of gastrointestinal symptoms but refers to parental concern that MMR might be responsible for his autism.

In Child 9 the referral letter has no mention of gastrointestinal symptoms and it proposes referral to what is described as “Dr Wakefield’s service.”

Child 5, the referral letter has no mention of gastrointestinal symptoms but refers to parental concern arising from reading in the Daily Mail about the MMR vaccine.

Child 10, the last of the four, the referral letter has no mention of gastrointestinal symptoms and refers to the father having heard of Professor Walker-Smith’s work and being keen for assessment. Not only that, but we say that the use of the phrase “consecutively refers” implies again to the reader, whether he be scientist, journalist, member of the public, a routine process of referral. That is, one in which another doctor asks for his patient to be seen, not one in which an active role is played by the research investigators in what I can only describe as, using as neutral a word as I can, obtaining the patient for the purposes of their study.

The circumstances of referral of these children were in a number of cases unusual and some of the GPs involved you will hear were surprised to receive calls directly from Dr Wakefield requesting them to consider referral. I should make it clear that the charges of misconduct relate not to each individual circumstanced because our experts entirely accept that unusual routes of referral, even if they are unusual, sometimes occur. Although they may be unusual, there is nothing inherently improper about a consultant contacting a GP directly in relation to a piece of research. What we criticise and what the charge relates to is, as I have said, the way it is subsequently described by these doctors in the published paper.

With regard to both Dr Wakefield and to Professor Walker-Smith, two children: Child 2, who was entered into the project after Professor Walker-Smith wrote to the child’s mother direct, ten months after he had last seen that child, saying that he had discussed the child with Dr Wakefield and the two of them had a plan for his investigation. Child 9 entered into the project after Professor Walker-Smith wrote, uninvited, to the child’s consultant paediatrician, asking for his referral, Dr Wakefield having provided Professor Walker-Smith with that child’s name. So, as I say, for those two the charges relate to Dr Wakefield and Professor Walker-Smith.

With regard to Dr Wakefield only, Child 2 was entered into the project after Dr Wakefield telephoned the child’s GP requesting a referral to Professor Walker-Smith, and Child 12 was entered into the project after Dr Wakefield telephoned the child’s GP saying he needed a colonoscopy, and again requesting a referral to Professor Walker-Smith. We say that in all those circumstances, the omission of a reference to the purpose of the investigations was dishonest and the description of the method of referral in The Lancet paper was wholly misleading and it was therefore irresponsible, because it was a distortion of the true position by Dr Wakefield and Professor Walker-Smith and thereby gave a false impression that the way these parents arrived at the Royal Free complaining of disability relating to MMR was, in effect, coincidental, when in fact far from being coincidental, the association with vaccination was necessarily bound up with the hypothesis under investigation in the research project and was therefore bound to be reflected in any report of the study.

The misleading nature of the statements made in The Lancet we say was a breach of their undoubted duty as senior authors of The Lancet paper, because the association between the gastrointestinal and behavioural symptoms on the one hand, and vaccination on the other, was not a discovery made in the course of clinical treatment of children routinely referred, but was the inevitable consequence of the fact that these children were selected for a study of that very association. We then say that that misleading description of the method of referral in The Lancet was compounded by both Dr Wakefield and Professor Walker-Smith on different occasions, and given the circumstances, when it was compounded in that way it became, frankly, dishonest.

I am going to deal with them separately. Subsequent descriptions of the referral by Dr Wakefield: It came about that there were subsequent descriptions after The Lancet paper, because inquiries were made and the importance to the scientific integrity of the paper of the issue of how the patients came to be investigated is highlighted by correspondence to The Lancet after publication of the paper, in which there was a suggestion that there may have been some sort of bias selection of patients. When those letters were written inquiring into that issue, Dr Wakefield responded to that suggestion in a letter dated 2 May 1998. It is in bundle 3 at page 924.

(After a pause) It is a letter that we will be looking at in relation to the charges relating to the litigation, but for these purposes its significance lies in two representations which are made in it. They are all in the middle column on that page, which starts off “A. Rouse” who is the gentleman who raised this issue, if you are with me about six or seven lines down in the middle column. Do not worry for the moment about that aspect of this letter; the relevant parts go on after the words “Legal Aid Board”. It says:

“These children have all been seen expressly on the basis that they were referred through the normal channels (eg, from general practitioner, child psychiatrist, or community paediatrician) on the merits of their symptoms.”

Then if you go down to the bottom of that paragraph you will see the words:

“Finally all those children referred to us (including …”,

and then it goes on to the numbers,

“have come through the formal channels described above.”

We say Dr Wakefield knew very well that that description was wrong. In the cases I have dealt with the channels were not normal and they were not referred on the merits of their symptoms and, again, he is charged with dishonesty in relation to that, giving misleading information and failing to comply with his duties as a senior author of The Lancet paper.

Then we go on much later to another incidence where the very same information was sought from Dr Wakefield and that was at a scientific meeting at the Medical Research Council later on in March 1998, which arose because the importance of the whole issue was such that a scientific meeting was convened by the MRC to examine the evidence relating to measles and measles vaccine to chronic gastrointestinal disease. You will be seeing the transcript later, but the issue of bias was raised again by the scientists present at that meeting and Dr Wakefield was asked about the way the patients had come to be investigated. He said this:

“All the patients that we have reviewed so far have come to us through their general practitioners or paediatricians by the standard route”,

and it is our case that to describe the route by which these patients came under investigation as standard was again dishonest and irresponsible and was said in the context of a very important scientific meeting where inquiries were particularly being made in order to enable a responsible evaluation of his survey.

I have said there was original dishonest and misleading information in The Lancet compounded by both doctors, and I am now turning to the way that that applies to Professor Walker-Smith. So the two charges with regard to Dr Wakefield are the letter that he subsequently wrote to The Lancet and the information that he gave to the Medical Research Council. As far as Professor Walker-Smith is concerned, his reiteration that the referral process had been a normal one was made much later when The Lancet itself came to investigate the whole circumstances of the paper in 2004. He made a statement, which is in Bundle 3 at page 1213 which was published in The Lancet. He dealt with the issue in considerable detail. It is under the words,

“A statement by Professor John Walker-Smith”.

I am sure we will be coming back to this at some point later, and indeed the circumstances of the investigation by The Lancet I shall be dealing with shortly – “shortly” in both senses of the word. I will tell you a little about it and also I will be doing it in a little while. It culminated in statements by the doctors involved in the drafting of the paper. This is Professor Walker-Smith’s statement. If you look down to the bottom of the last paragraph,

“These children were referred to the Royal Free by their general practitioner (ten cases) or consultant paediatrician (two cases). Some parents had heard of Dr Wakefield’s previous work on inflammatory bowel disease and specifically requested referral, but the channel of referral was always as described above. However, the pattern of referral was often that the parents of the children approached Dr Wakefield directly knowing of his work, frequently by telephone. In the case of one patient, in whom it has been alleged that I contacted a consultant in order for a referral to be made, he had been asked by the parents of this child to contact me to explain what investigations were available at the Royal Free for children with autism and bowel problems. To the best of my recollection, I did not invite any children to participate in our study”.

Remembering the circumstances of Child 2 and Child 9, which I enumerated to you a little earlier, both of which we say involved an express approach by Professor Walker-Smith, we say that that denial was dishonest and, again, misleading in circumstances where allegations of impropriety were by that time being made. The context of Professor Walker-Smith’s denial arose because, in 2004, an investigative journalist – Mr Brian Deer – embarked on an investigation more wide-ranging than the matters that the General Medical Council is now considering, into the whole issue of the MMR vaccine. He made a number of allegations to Dr Horton, the editor of The Lancet about the conduct of the three doctors. As a result of that Dr Horton instigated his own inquiries by meeting with the three doctors. At that meeting with Dr Horton, from whom you will also be hearing, Dr Wakefield told Dr Horton that some of the children – he mentioned the numbers as 3 to 5 – whose results had been published in the 1998 paper were children who had also been investigated for a study commissioned by the Legal Aid Board.

The notes relating to the disclosure of conflicts of interest to The Lancet at the time the paper had been published in February 1998, which were regularly I should say published in the journal so that anybody submitting a paper to the journal should have been aware of them, were as follows:

“The conflict of interest test is a simple one. Is there anything – e.g. a shareholding in or receipt of a grant or consultancy fees from a pharmaceutical company, or a contract from a medical devices manufacturer, that would embarrass you if it were to emerge after publication and you had not declared it? The editor needs to be informed and will discuss with you (the author) whether or not disclosure in the journal is necessary. All sources of funding must be disclosed as an acknowledgement in the text”.

Dr Wakefield had not, on submission of The Lancet paper, told Dr Horton about his involvement with the litigation, nor the Legal Aid Board money he had received for his research. Thus, we say, Dr Horton had never had the opportunity to consider the impact of those matters on the paper prior to its publication. This is a matter on which you will be hearing from both our experts, both of whom are highly critical of the issue and who, of course, are looking at it not from the point of view of the editor of a scientific journal, but from the point of view of being someone who was in the position that Dr Wakefield was; namely, people with huge experience of submitting research papers to medical journals. They are both highly critical of this issue. Professor Booth’s view is that this was a clear conflict whereby, he says, the apparent research hypothesis was driven by a need to support successful litigation against the vaccine manufacturers. Professor Rutter’s view is that there was certainly a substantial conflict of interest with respect to lever funding running together with the research.

Having said that, it is our case that in fact, although our experts expressed the view that there was indeed a conflict of interest, the real issue is not confined to whether or not there was actually such a conflict – although of course that is highly relevant – but rather that the circumstances plainly raised issues which should have been disclosed in order that Dr Horton could consider The Lancet’s position. You may wonder why ever they were not, given that Dr Wakefield had been put on notice by his own Dean, Professor Zuckerman, that the conflict of interest issue was a very real issue.

Subsequently nine of the 12 co-authors of The Lancet paper, including Professor Walker-Smith and Professor Murch, signed a retraction of that paper which was published in The Lancet. The remaining three were one who could not be contacted; Dr Harvey, the neurologist involved in the original Project 172-96 and Dr Wakefield. The retraction was entitled, “Retraction of an interpretation”. It stated that in the original The Lancet paper, no causal link was established between MMR vaccine and autism as the data was insufficient. The possibility of a link was raised and consequent events had had major implications for public health. In the light of that, the signatories, including as I say Professor Walker-Smith and Professor Murch, formally retracted the interpretation placed on the findings in the paper.

In addition to the non-declarations in The Lancet, you will also recall a charge relating again to Dr Wakefield of failing to disclose the same involvement in the litigation and the Legal Aid Board funding to the Ethics Committee. Our experts are similarly critical of that, they say, material non-disclosure.

During the General Medical Council investigations, another matter came to light which, in the view of our experts, also constitutes a conflict of interest on Dr Wakefield’s part, which should have been declared to The Lancet at the time of the publication of the paper. That relates to a patent application in respect of a substance called “transfer factor”. In June 1997 Dr Wakefield – I should say again and underline, as I keep having to do, that this again is a matter that involves Dr Wakefield only – instructed patent agents to file with the UK Patent Office a new invention which he sought to patent. That, as I said, was a substance known as “transfer factor”.

You are going to be hearing briefly from an expert, Professor Sir Peter Lachmann, about what transfer factor is, and I am only going to attempt to embark on it in the briefest of terms for present purposes. In the briefest of terms transfer factor is a naturally occurring component of the immune system which can be produced specifically to target a particular virus and thus used as a therapeutic agent to treat complications arising from the failure of the patient’s own immune system to clear that virus. The patent application is at Bundle 2, page 479. In fact 479 is a patent agent’s details in relation to the registration of that patent, and if you turn over to 480 you will see, “The pharmaceutical composition for treatment of IBD and RBD”. I am only going to refer to a very small number of parts in it. More of it may be relevant later but for present purposes those are the only parts we want to draw to your attention.

If you look down to line 20, just below that,

“At present vaccination is used for the prophylactic prevention of measles virus and as a public health measure has proved to be generally effective”.

Underneath that,

“Unfortunately as I have shown previously in the above mentioned patent application the use of this vaccine has been shown to be instrumental in development of Crohn’s Disease and other forms of IBD over the ensuing 30 to 40 years and particularly has been instrumental in a substantial increase in Crohn’s Disease in children since vaccination was started in 1968”.

So this is a reference by Dr Wakefield back to his original work that I mentioned to you yesterday.

“The Physician is therefore confronted with a difficulty at the individual level in that whereas as a public health measure measles vaccination is called for, it can have unwanted effects in those subjects who are unable to immunologically eliminate the virus so introduced”.

He goes on just above line 10,

“What is needed therefore is a safer vaccine which does not give rise to these problems and a treatment for those with existing IBD. I have now discovered a combined vaccine/therapeutic agent which is not only most probably safer to administer to neonates and others by way of vaccination, but which also can be used to treat IBD whether as a complete cure or to alleviate symptoms”.

That is as far as I need to go at the moment to make the point that that patent clearly envisages the production of this substance, “transfer factor” as both a treatment, a therapeutic agent, and a vaccine. Our experts’ view is that in such circumstances it too should clearly have been disclosed to the editor of The Lancet. The Lancet paper, albeit anecdotally, is suggesting that children were at risk if the MMR vaccine were administered. At the same time as that, Dr Wakefield was embarking on an enterprise to invent a new kind of vaccine and was, by registering a patent, protecting the intellectual ownership of that new vaccine. Potentially, at least, that vaccine would be a rival to the MMR vaccine, at least and if only in those cases where it was appropriate for it to be given.

So it is our case that Dr Wakefield had a role, a dual role as an investigator and with a potential financial interest, and in those circumstances, the potential for conflict is clear and the disclosure should have been made in order for others to judge the position.

I turn on to a completely separate matter, which relates only to Dr Wakefield. It is in your heads of charge headed, “The birthday party”. It arises out of the lecture that Dr Wakefield gave a considerable time later than the matters which you have so far been considering, but out of a related subject since the lecture was to an audience at the MIND Institute, which is an acronym for the Medical Investigation of Neuro-developmental Disorders” in California in the United States on the subject of the gut/brain axis in childhood development disorders. That lecture was video-taped and he gave an account of an incident in it relating to the taking of blood at the birthday party of his son. You will be seeing the video later but for now I am simply going to quote for you what Dr Wakefield said. I should say that there are a few short pauses in it where it is inaudible for some reason.

“Again, for those who have heard the story, you can put your hands over and you can take time out here, but this is again my son’s birthday party. Thirty-two healthy controls and you line them up, with informed parental consent of course. They all get £5, which doesn’t translate into many dollars I am afraid, but, and they put their arms out and had (inaudible) and they had the blood taken, entirely voluntary. And when we did this at that party, two children fainted. One threw up over his mother, one child, who is my son’s best friend [name given] he put his arm out, very bold, had the tourniquet and then went pale and sort of, wait till next year. He was nine at the time, and his four year old sister came up, stuck her arm out, had the blood taken, took her £5 and went off. And then [child’s name] burst into tears. Ruined his birthday party. But people said to me, ‘Andrew, look, you know, you can’t do this. People, children, won’t come back to your birthday’. I said, ‘You are wrong’. I said, ‘Listen, we live in a market economy. Next year they will want £10’. And we have a birthday party coming up as well when I get back, so we will be going. They charge me a fortune. Urine, I mean, come on, but they were all less than 10 years of age and none had been revaccinated against measles and none were within 18 months of vaccination. So these were two comparable groups”.

So that is a clear explanation of why this blood was important, in the last words that I read out to you, because these children were normal children and could be used as “controls” – a phrase I explained yesterday – when doing research into this issue. That account has to be considered against the background of the circumstances in which it is possible to take research samples from children. I am going to quickly refer you to some specific parts of the guidelines. Obviously in this case, this research is completely non-therapeutic since it is being done on normal children simply to get blood for control purposes. That means that it carries risk, albeit a small one, and no benefits.

I am going to remind you again of a passage in the Paediatric Association Guidelines because although I say the risk is small, you have to bear in mind we are not just talking as we would in an adult about the physical risk, but also about the risks to the child’s wellbeing in much more general terms. So please go back to Bundle 4, page 188. That is the document that I referred you to yesterday, and you will recall what it says. It sets out the minimal procedures first of all and then says:

“Low risk describes procedures that cause brief pain or tenderness, and small bruises or scars. Many children fear needles and for them low rather than minimal risks are often incurred by injections and venepuncture.



It would be unethical to submit child subjects to more than minimal risk when the procedure offers no benefit to them, or only a slight or very uncertain one. Higher risks in research and novel treatments are accepted when children are enduring very harmful disease … etc.”

So the clear position is that if the risk is more than minimal it should not be carried out for non-therapeutic reasons, as this one was.

Secondly, of course, you should remember that all research requires ethics committee approval.

Lastly, you are going to be hearing evidence from Professor Booth both as to the fact that it was very hard to get blood from normal children for research purposes for these very reasons, and clinical researchers devote a great deal of time and energy to obtaining blood samples from normal children in an ethical way. Children who are patients and who need a blood test usually need it because of some clinical condition and therefore the blood that you collect cannot confidently be called “normal”. One of the ways, as Professor Booth will tell you, as a paediatrician and a researcher who has to confront this problem, of achieving blood ethically is through a cannular which has to be inserted in a way for a surgical procedure, and, provided an ethical committee has approved it, provided they have, it would then be acceptable for a researcher to take a small amount extra for research purposes. So that is the context and background against which you must look at this account of the way in which Dr Wakefield apparently feels it is appropriate to cope with the difficulties in getting normal blood for control purposes in research.

We have no evidence other than Dr Wakefield’s own account of this incident, but it is our case that there can really be little better evidence than that. You are going to be hearing from both our experts, Professor Booth and Professor Rutter on this incident, if it occurred as Dr Wakefield tells us, that it was not remotely acceptable as a method of getting normal blood. It broke every principle of ethical medical conduct. A social setting with the implication of peer or apparently parental pressure, to please or to conform, the offer of a financial inducement, the fact that on Dr Wakefield’s account some of these children were plainly upset, and, indeed, more than upset, are all of relevance. The charge as it is set out, and you can read again later, reflects our case that not only was this unacceptable conduct but that recounting it in what we are going to invite you to find when you hear the video, in the most flippant and frivolous of terms was so inappropriate as to bring the medical profession into disrepute.

That is the birthday party charge.

I am now turning on to the issue of the individual children involved in the study, and I see, fortuitously, it is bang on 1 o'clock and this really is a new subject and it is one where you are going to have to refer to lots of new medical records, so would this be the appropriate moment to break?

THE CHAIRMAN: I have got no idea how you organise your natural pause to be so absolutely and precisely on the minute, but thank you very much. It has been a long and intense session, and I think we will now break for lunch. We will resume at 2 o'clock.

(Luncheon adjournment)

THE CHAIRMAN: Good afternoon. Just a reminder, can everybody please ensure their mobile phones are switched off while in this chamber? Ms Smith?

MS SMITH: Sir, before I go on with my opening, Mr Miller raised two matters with me during the luncheon adjournment in respect of his client and he asks me to clarify what I said, and I am very happy, of course, to do so. The first was that when I was describing the description that Professor Walker-Smith had given of the referral process in 2004 when the matter was investigated by The Lancet, I used the phrase “his reiteration that the referral process had been a normal one” and Mr Miller has asked me to make it clear that if by the word “reiteration” I was referring to the original description in The Lancet paper, which indeed I was, the words “the referral process had been a normal one” had not been used, and that is perfectly correct. I hope you understand that the GMC’s case is that in respect of The Lancet paper that the descriptions that were given were misleading and then, as I say, when Professor Walker-Smith was asked to give more details in relation to it we then say that his description was a dishonest one, but it is absolutely true that it was not a reiteration of what was said in The Lancet paper. That is the first clarification.

The second clarification is that Mr Miller tells me that when I referred when I was talking about the retraction of the interpretation of The Lancet paper that I said “a retraction of the paper” at some point, and that also was an inaccuracy by me. I think you will appreciate that. The retraction was entitled, “The retraction of an interpretation” and was in the terms I set out to you this morning, but it was not intended by the authors to be a retraction of the entire scientific paper, and that also I entirely acknowledge.

I hope that puts both of those matters right.

I am going to turn on to a rather more consideration of the children that we have so far had, and, first of all, I want to make clear the nature of the tests which you will be hearing about in great detail from now on during the hearing. I have touched on definitions of them both but I would like to look at them in a little more detail. The two tests carried out on the children which the charges focus on, both of which we say are highly invasive, and we say were done in the vast majority of cases when they were not clinically indicated were colonoscopies, which was usually accompanied by a barium meal and follow-through, and lumbar puncture, and it is those two that I wanted us to be clear about.

As far as colonoscopy is concerned, a colonoscope is a narrow, flexible, fibre-optic telescope about a metre long, which is used to examine the colon. The patient undergoes a bowel preparation the day before the procedure is being carried out by being a laxative to ensure that the bowel is empty and by having nothing to eat or drink for several hours before the procedure, and then the colonoscope is inserted via the rectum and the doctor examines the colon either directly down the colonoscope or on a screen. That is why we say it is a highly invasive procedure, and it is one which our expert, Professor Booth, describes as being not without risk. There is a small risk – that is less than 1 per cent – of perforation of the colon itself, an occurrence which has potentially, obviously, serious consequences, and, in addition, there is a risk, albeit we entirely accept a very small one, of haemorrhage.

Professor Booth quotes from a 1992 textbook on the subject:

“Total colonoscopy in children involves real stress. The colon must be thoroughly prepared since only a clean colon can be examined. Neuroleptanalgesia (deep sedation) or general anaesthetic is necessary since stretching of the sigmoid loop, which cannot always be avoided, often gives rise to intense pain.”

Of course, neither heavy sedation nor general anaesthetic of themselves either are free from risk.

The children you are going to hear about all suffered from behavioural disorders of varying degrees of severity, and their ages ranged from just under three to nine and a half years old. All in all, when I read that description out to you, you will not be surprised to learn that in clinical medicine colonoscopy is carried out on children when there are very real indications to do so, and Professor Booth will again be referring you to the relevant literature in 1992, which gave as indications for colonoscopy recurrent rectal bleeding or suspected chronic inflammatory bowel disease. Chronic inflammatory bowel disease, may I remind you, as I mentioned yesterday, covers two main conditions as well as some very much rarer ones. The two main ones being Crohn’s disease and ulcerative colitis.

You should bear in mind when you are hearing about these children that constipation is not a symptom which indicates the need for colonoscopy. Even if a child exhibits symptoms which may be said to fall into one of the categories that I have mentioned, there are other steps, falling short of invasive investigations, which can be taken in order to see whether there are signs of inflammation which warrant proceeding to invasive investigations, and those steps involve blood tests to look for inflammatory indices in the blood.

Given the non specific nature of some of the presenting symptoms and the invasive nature, particularly for children, of the procedure envisaged, the decision to refer for colonoscopy must, we say, be very carefully considered and blood tests can, and in our expert Professor Booth’s view should, be used as screening tests to indicate whether further steps should be taken. So that is the colonoscopy procedure. As far as barium meal and follow-through is concerned, that involves a procedure where a patient is given a drink containing barium sulphate and a series of X-rays are taken over a period of some time to see the passage through the gut. The patient has to have nil by mouth for some hours before the test. It may or may not be accompanied by a drink to cause the stomach to expand with gas and/or an injection to relax the stomach muscles, and we shall have to ascertain the precise nature of it on these various occasions. Its possible side-effects may be a feeling of nausea afterwards, and it may cause constipation, but most importantly of all, of course, it exposes the patient over, as I have said, quite a long period of time to irradiation.

As far as lumbar puncture is concerned, lumbar puncture is a procedure where a sample of cerebrospinal fluid is taken for testing. The sample is taken by the insertion of a needle between the two vertebraes at the base of the spine into the spinal column. It is therefore, again, an invasive procedure and there are risks associated with it, although they are rare. It is a procedure generally undertaken under local anaesthetic, but in the case of these children was sometimes done under a general and sometimes at the same time as the colonoscopy and sometimes not.

It is acknowledged by our expert, Professor Sir Michael Rutter, that a lumbar puncture might be clinically indicated in circumstances where a neurologist or a psychiatrist with the requisite expertise took the view that the symptoms were such that a diagnosis of disintegrative disorder should be explored, but it is his expert view that the need for lumbar puncture in those circumstances, in other words where there is suspected disintegrative disorder, is one for a neurologist or a psychiatrist with the requisite expertise and not, as frequently occurred in these cases, gastroenterologists, and also that it is never clinically appropriate as a diagnostic tool for the condition of autism.

As far as the children are concerned, I will hand to the Panel in a moment a spreadsheet which I hope will be useful for everyone, including the defence, which sets out exactly which child is charged is respect of which particular head of charge. In fact we can do it now as they are to hand. There are three spreadsheets one for each doctor, and you should bear in mind that they deal only with the children who are written up in The Lancet paper. I am giving them to you because I hope and believe they will be very useful to everybody. You will not need them for the rest of the afternoon because I am going to go through the charges with you but they will be an aide-memoir for the future and will enable you to see at a glance the charges in relation to the particular patient. (Same handed and marked as Dr Wakefield C1: Professor Walker-Smith C2 and Professor Murch C3).

First of all, I will deal with these children in the chronological order in which they were seen by these doctors. Can I say to begin with, all their names have been anonymised and we have been referring to them by the numbers that were ultimately used when they were written up in The Lancet article. It is absolutely inevitable that somebody at some point is going to make a mistake and refer to a name inadvertently, and I have to say it would be a miracle if I get through the opening without doing so because I am going to be referring to medical records where they are, of course, named. I wonder, sir, if you would think it appropriate at this stage to request that the media really do respect the privacy of these children and that if I make such an error that they do not report it.

THE CHAIRMAN: Yes, indeed. Can I make this request to everyone who is present here: if the names are inadvertently divulged for one reason or another, can you please make sure that you do not report the names in any correspondence or in any reporting whatsoever. Thank you. Refer to the children only as numbers.

MS SMITH: The way in which I propose to approach this is that the first witnesses from whom you are going to be hearing will in fact be, we hope, the GPs as to the background of the arrival of the children at the Royal Free in order to put them into the context of their medical histories.

I am going to try and briefly summarise that part of the history to you in opening and go into a little more detail in relation to the Royal Free records from the time of their referral onwards, and then, as I say, you can hear the background context of that referral when the GPs deal with their own general practice records. You should bear in mind, before we dive into the individual circumstances of each child, that it is not just the clinical circumstances that you should be looking at, although they are, of course, important, it is also about the ultimate description of the project in the ways that I have already outlined to you in The Lancet paper when it was ultimately submitted.

The first child to be seen – I will tell you when you need to extract the medical records in relation to each child, but in respect of this one it will not be for a page or two.

The first child, somewhat confusingly, child two, was the first child to be seen by Professor Walker-Smith. He was a little boy born in July 1988. When he first came to the attention of Professor Walker-Smith it was when Professor Walker-Smith was working at St Bartholomew’s hospital, prior to his employment at the Royal Free Hospital. The professor saw him again at the Royal Free Hospital in June 1996 when he was nearly eight.

That little boy’s background was that he had had his MMR vaccination in November 1989 when he was 16 months old. He had never had either a measles or an MR vaccination. The first mention, in the records at least, of possible behavioural problems was in January 1991 and a year after that he developed chronic diarrhoea. His GP, from whom you will be hearing evidence, is a Dr Cartmel, and Dr Cartmel describes Child 2 as a unique child from the point of view of the clinical picture that he presented. Dr Cartmel first became Child 2’s GP when Child 2 was three years old. His parents at that stage gave a history of normal development at first and then of regression, and Dr Cartmel made a note in the records that Child 2 had already had a brain scan which had shown nothing abnormal, that he had a high level language problem and was believed, at any rate by his family, not to be autistic.

By April 1992 it was thought that he might have an allergy-induced autism, and it is Dr Cartmel’s recollection that from early on the family thought that MMR was implicated in his problems. He was seen in September 1992 by a Professor of Child Health at Southampton Hospital, who thought that the best label that might be attached to him was one of Asperger’s syndrome, which you will probably have heard of as a relatively mild form of autism. In November 1992 he was seen by another consultant paediatrician at Southampton who had a particular interest in coeliac disease, which is, as you probably know, a reaction to the gluten protein found in wheat, and this particular paediatrician had an interest in the connections between that disease and autism, and he entered Child 2 into the autumn assessment service at Southampton for further in-depth investigation.

In August 1993 he was referred to a paediatric neurologist at the Chelsea and Westminster Hospital, who could not find any neurological abnormalities, who felt his history pointed to dietary sensitivities and indicated that the parents wanted to explore the possibility of a B12 deficiency through the B12 unit, which was a very specialist unit which existed at that time at the Chelsea and Westminster Hospital.

At the same time his GP also referred him to a local consultant paediatrician and ultimately asked him to take over what he described as the clinical driving seat in relation to the consultations which had been arranged in respect of this little boy, and he was then referred on to a consultant child psychiatrist, who is a gentleman called Dr Wozencroft. In June 1995, at the request of Child 2’s mother, Dr Wozencroft referred Child 2 to Professor Walker-Smith. As I have said, at that time, in June 95, Professor Walker-Smith was working at St Bartholomew’s Hospital, not at the Royal Free. That letter we should read, and it is in Child 2’s Royal Free Hospital records, and if you turn to page 197 of those records, letter of 20 June 1995 to Professor Walker-Smith at St Bartholomew’s from Dr Wozencroft, Child Psychiatrist:

“Dear Professor Walker-Smith

I write to ask you to see [2] and to express an opinion upon him. I know that his parents have contacted you and your colleague, Andrew Wakefield. The family doctor, Dr Cartmel, also wants the benefit of your opinion.

[2] is a boy who has been seen by a great many doctors over the years. I have become involved only recently. My tasks are to take an overview of the situation; to follow [2]’s development and to discuss it with the parents and to help the family find their way to any source of medical help which might be available.

At present [2]’s condition in Child Psychiatric terms falls within the diagnostic category of Autistic Spectrum Disorder. Plainly, such a disorder can arise through more than one mechanism. Mr & Mrs [2] feel that there is a strong physical component to [2]’s difficulties. I must say that I agree with them. At the moment, [2]’s physical, medical and emotional states are all deteriorating. In the past, just such a deterioration has been nipped in the bud by B12 injections. I think it entirely legitimate for Mr & Mrs [2] to be seeking your expertise.

For my part, I am not familiar with the research evidence which connects immunisation with difficulties like [2]’s. Naturally I am trying to educate myself in that area. [2]’s condition, however, is going downhill again and his parents, his GP and I would all be grateful for an urgent opinion from you.”

Now, you should bear in mind that that letter was written more than a year before Project 172-96, about which you are hearing, and we say that Professor Walker-Smith’s approach at that time was a very proper one, consistent with a clinical as opposed to a research referral, and that that was in contrast to the later occasion when he saw Child 2, to which I shall be referring shortly, and to the way in which subsequent children were treated.

So I am going to deal in some little detail with what happened at that earlier stage. In August 1995 he saw Child 2 in response to Dr Wozencroft’s letter, and he wrote back having done so, and the letter he wrote is on page 196, the previous page, and he said:

“Many thanks for referring this child. Clearly this is a very difficult problem. I am left somewhat confused as to what the evidence is of B12 deficiency …..

On examination there is no evidence of Crohn’s disease which concerned the mother, in view of the possible association between measles and Crohn’s disease. Apparently there has been a gastrointestinal problem in the past and I am writing to the various professionals to try and find [out] what has been done in the past and I plan to see [2] again in 2 months time.

One of my former research fellows ….. as you know has come to Peterborough as a consultant paediatrician. Mother is saying that she has not had a consultant paediatrician concerned with the overall management ….. and I think it [would be] helpful in due course for [him] to see [2].

However I plan to see him myself again in 2 months time when I have more information available. I have done some routine blood tests.”

After that Professor Walker-Smith embarked on a series of inquiries as to what others involved in Child 2’s care had done. He wrote to the B12 unit, and you can see that letter on page 194, and he said in that letter:

“I understand from Mrs [2] that you have been investigating [2] quite extensively for evidence of B12 deficiency. I would be very grateful if you could let me know ….. your opinion ….. of B12 metabolism in this child”.

He said again that he would be seeing him in two months’ time. He wrote to the paediatric neurologist who had been involved, and that is page 193, and he said he was puzzled by the child:

“and am interest in your letter where you consider the diagnosis of Vitamin B12 malabsorption, I am a little unclear as to what investigations have been done ….. I would ….. be very interested if you could outline for me your assessment of the child.

The child was referred to me via Andy Wakefield of the Royal Free because of mum’s perception of the childs illness really began with MMR and in view of the possible link of measles with Crohn’s disease.

On examination there is absolutely nothing to suggest the diagnosis of Crohn’s disease. His weight and height are both close to the 50th centile. The gastrointestinal story sounds very much like multiple food allergy/irritable bowel syndrome rather than inflammatory bowel disease or indeed coeliac disease. However I have done routine blood markers, CRP, endomysial antibodies etc, and I plan to review him again at the Royal Free in 2 months time.

In the meantime I would be very grateful if you could send my ….. your opinion.”

He furthermore wrote to the Professor of Child Health at Southampton, and that is at page 195.

“I would be very grateful if you could give me your opinion on this child whom is diagnosed as having autistic syndrome and has had evidence in the past of multiple food allergy ….. some history of possible B12 deficiency.

…..complicated problem and I would be grateful for any assessment that you may have made concerning him.”

Professor Walker-Smith concluded that the best way forward was as advised by the B12 unit for Child 2 to undergo the investigations that they had already planned, namely a Schilling test, and ultimately in September 1995 Professor Walker-Smith reverted to the GP Dr Cartmel, and that letter is at page 178:

“Dear Dr Cartmel

I have now reviewed [2] and I think inflammatory bowel disease is extremely unlikely and I have had a copy of the letter which Dr Bhatt” – he was the consultant at that time at the B12 unit – “wrote to you and I do believe that the best way forward is for a Schillings Test. This is a test which is best done by experts and I would recommend that this is done in the Chelsea & Westminster.”

He felt it would be helpful if a paediatrician could be locally involved and suggested a recently appointed consultant at Peterborough, and he said:

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

He wrote to Dr Wozencroft, the Child Psychiatrist who had referred originally, and that is at 179, and he made the very same point:

“After reviewing [2], I don’t really believe there is any evidence of chronic inflammatory bowel disease and I think that the next way forward is ….. to do a Schillings Test ….. apparently already planned …..

I have not made an appointment to see [2] again, but I should be happy to do so ….. in the future and I have left the line of communication open with Mrs [2]”,

and again a reference to the paediatric consultant at Peterborough. Now, the significance of those letters is that it is plain that Professor Walker-Smith did not see any evidence of chronic inflammatory bowel disease or apparently any reason to investigate this child further, and at that stage you will note that there was no question of Professor Walker-Smith suggesting that Child 2 might need or did need a colonoscopy.

Thereafter, Dr Cartmel and one of his GP colleagues referred Child 2 to two more consultants at different hospitals, a consultant gastroenterologist at Addenbrooke’s, who suggested trying Child 2 on an exclusion diet and probiotics, that is bacteria, but did not suggest any more invasive investigations, and a consultant biochemist at Peterborough Hospital who concluded that there was no evidence of a vitamin B12 problem.

The next step in the story as far as the ultimate investigations of this child are concerned was on 16 May 1996, so ten months after he had first seen Child 2. Professor Walker-Smith wrote, apparently at least as far as one can tell from the medical records, unprompted to Child 2’s mother. The letter that he wrote is at page 165 of the Royal Free records.

“Dear Mrs [2]

I think it would be very helpful if I saw [2] again. I have had discussions about [2] with Dr Wakefield. We have a plan for investigation but I think if it were convenient for you, it would be helpful for me to see [2] first in the outpatients and discuss and plan what we have in mind. I have arranged an outpatient appointment for 9.30am on Friday 14 June which I hope may be convenient for you.”

That letter is at page 165, sir. In fact, Child 2 next saw Professor Walker-Smith when he attended outpatients a few days later than that on June 21, and by that time Professor Walker-Smith was at the Royal Free Hospital. During that consultation Professor Walker-Smith arranged for Child 2 to undergo blood tests, and you will recall what I have said briefly in relation to those: in the presence of inflammatory bowel disease, blood tests can be used to see if there are any signs of inflammation detectable in the blood. When they are normal, inflammatory bowel disease is an unlikely diagnosis. Blood testing is therefore helpful in deciding whether an invasive procedure of colonoscopy is really necessary. In the event of this child the step was taken first, and Child 2’s results subsequently demonstrated that the indices of inflammation were normal.

Professor Walker-Smith then wrote to Dr Hunter, who was the gastroenterologist who had seen him at Addenbrookes, who I mentioned briefly earlier, and his letter is on page 163:

“I would be very interested to hear your view concerning [2]. I understand that you are seeing him and that he has had a good response to food elimination ….. I would be most grateful if you could let me know what regime he had and your thoughts about him. Via Andy Wakefield I have been asked to see him to consider doing a colonoscopy and a general assessment as to consider whether bowel inflammation of some kind might be playing a role in his illness, and also performing Schilling Test which has not been performed as there had been some concern about B12 metabolism in the past”,

and indicating that he would be interested to hear his comments in general; i.e. that seems to be suggesting that he was going to investigate the bowel inflammation which he had apparently already ruled out. On the same day he wrote to Dr Wakefield, on page 162:

“Dear Andy

I at last saw [2]. I think he is now the most appropriate child to begin our programme. Can we discuss together the most appropriate date? I think September might suit Mrs [2] best. She has some apprehension about colonoscopy and she was concerned that last time [2] had a general anaesthetic he reacted with a transient fall of blood pressure. In fact we will not be using a general anaesthetic but it is difficult to judge whether he might in any way react to pethidine. I think she would like a copy of the protocol that we are using. I don’t know whether you think it is appropriate for you to send her that or whether I should.”

So that was how we say Child 2 came to be investigated according to Dr Wakefield’s protocol, and, as you know, we say that that was clearly a research protocol, and indeed that is reflected in the correspondence that I have just read to you, the protocol which became Project 172-96, although you will recall that this arrangement in June 1996, as evidenced by that letter written on the 21st, was well before any application had been made to the Ethics Committee.

On 28 June Professor Walker-Smith wrote to Dr Cartmel, the GP, and that letter is at page 130:

“Dear Dr Cartmel

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

It is our case that that letter is a very significant letter. Child 2 has come to the attention of Professor Walker-Smith through Dr Wakefield, and the reason for that was Dr Wakefield’s interest in measles immunisation. The plan was that he was to be investigated under a programme designed for the purposes of looking at the association of autism and immunisation, i.e. it is our case clearly a research programme, and the investigations were to be carried out on the basis of a theory, a scientific theory, of Dr Wakefield’s as to some kind of inflammation, presumably we say outwith the conventional clinical picture, since Professor Walker-Smith had already concluded that Child 2 did not have that conventional clinical picture.

Prior to his admission to the Royal Free for that colonoscopy, as a result of another referral Child 2 was seen by a paediatric neurologist at Great Ormond Street, who diagnosed him as autistic but noted that there was a feature of an unusual regression. In addition, Professor Walker-Smith received a letter from the gastroenterologists at Addenbrook’s, to whom I have previously referred, indicating that Child 2 was greatly improved gastointestinally when he stuck to his diet and the bacteria that he had been having.

After that, and despite that, Dr Casson, Professor Walker-Smith’s registrar – and you will remember there is an issue about this, that he is a lecturer in the university and had an honorary contract as a senior registrar – wrote to Child 2’s parents arranging for his admission for colonoscopy and indicating that any other further investigations would be decided on another occasion following consultation with Dr Wakefield.

Child 2 was ultimately admitted on 1 September 1996. A consent form was signed for colonoscopy and all the other investigations and that was a standard clinical consent form, not a research consent form, and I can show that to you. It is at page 340. That lists colonoscopy, biopsy, Shilling test, lumbar puncture, MRI scan, and it is a consent form, as I say, in the standard form for a clinical procedure. You will recall the different nature of the consent form and the patient information sheet which are attached to a research project, and of course because it is research, going to very considerably more detail and information. That was not apparently the consent form used for this procedure.

Our gastroenterology expert, Professor Booth, is critical of the decision to undertake colonoscopy. Child 2’s symptoms, in his view, were unclear, but plainly they had not suggested inflammatory bowel disease at the time of his initial consultation, the changed view apparently being brought about as a result of Dr Wakefield’s views as to a link with immunisation. In those circumstances, it is our case, as reflected in the charge, that it was not clinically indicated but it was a research investigation.

MR MILLER: Sir, if this is intended to be a reference to all of the relevant consultations that led up to the admission, I wonder whether Ms Smith would be prepared to turn up what she has not done, the outpatient clinic notes which we have in the bundle?

MS SMITH: Can I assist in this? I do not think anyone really wants to know all the mechanics of the way in which I design my opening, but I think it would be helpful to say this. I have not referred to the actual outpatient notes because I find the doctor’s handwriting almost impossible to read, if I have to read it out to a Committee in large amounts. So, what I have done in respect of each child is only to refer to it if the symptoms are not subsequently reflected in the general practitioner’s letter. If they are subsequently reflected, ie when Professor Walker-Smith writes back to the general practitioner and says what the symptoms were that he saw in out patients, then I have not referred to it. I am very happy to refer to outpatient notes, but as I say, they are very long, some of them, and without knowing precisely which bit Mr Miller wants me to refer to it is going to be a rather tortuous process if I have to read out the entire notes.

MR MILLER: My concern is you get a slightly skewed view about the process of referral and if you do not see that there has been a return visit to see Professor Walker-Smith at his clinic, in which symptoms of diarrhoea are described there, you get the impression that the reason for the admission is purely because of a conversation with a fellow colleague. If one is going to go through this to see the sequence and if the Council is going to attach significance to that sequence, it is very difficult to do so if you leave chunks of it out. We have also, for what it is worth, left out the part played by the Great Ormond Street Hospital and the paediatric neurologist there, who examined this child and made certain recommendations.

MS SMITH: I think I should say this. First of all, it might have been helpful if this had been raised – because it is going to arise, I suspect, in respect of a lot of children – before, rather than at this point in my opening. You have seen the size of the medical records. I said to you originally that generalisations inevitably carry inaccuracies. I have to be selective when I am opening the case to you in respect of the information that I give you. I try not to make that selection unfair, but obviously I draw attention to the matters which I contend are relevant to the case that I am putting before you. The general practitioners are being called, the experts, of course, are being called. There are going to be many, many opportunities to go through these records and for Mr Miller to highlight those matters which he particularly wants to refer to. But, as I say, I take the point in relation to the one point about the symptoms that are being indicated by the child, and myself and my juniors did a very careful exercise in ensuring that if symptoms are in the outpatient appointment clinical notes they were reflected in the letter to the GP – as of course they should be – so that when you read the letter from the GP you can see the central symptoms.

If I have to take some other course, well then, I will have to re-look at every single one of these cases, because you can see, as I say, the volume of the medical records behind you. It seems to me that I must do the best I can to present the picture which, as I say, I do not wish to be unfair about, but I have to make the points that we say are relevant to the case that we are putting before you. Mr Miller will have lots of opportunities to show why he says that is not fair in some way at numerous points during the trial, including when the GPs are called first of all.

MR MILLER: Sir, with respect, that is not really good enough, because what the Council are supposedly doing now is identifying the medical records which they say support the case. The implication for this particular charge is that Professor Walker-Smith saw this child, found no evidence of IBD and did not see him again, and suddenly, for a reason which is unconnected with symptoms being displayed by that child, chose to have him back into clinic a year later. If you are going to follow that line you cannot jump over the intermediate steps, where there is clear evidence from an outpatient clinic visit that there were symptoms there which were different from the symptoms that were being displayed before. That is my only point.

THE CHAIRMAN: Legal Assessor?

THE LEGAL ASSESSOR: Obviously, when opening a case it must be a fair presentation of the evidence, but obviously it is a selection of the evidence which is going to be referred to which supports the case of the person who is currently opening the case, namely prosecuting counsel for the General Medical Council. Mr Miller will have the opportunity both to cross-examine the witnesses called to these medical records and put to them the points he seeks now, and equally before he calls any evidence, if he is going to call any evidence at all, whether or not he calls any evidence, he is allowed to make an opening statement on behalf of his client when he could redress the balance, as it were. If it is going to be inconvenient for Ms Smith to take on board particular references at this stage in her opening, she cannot by any of us be obliged to restructure her opening. How she opens the case must be a matter for her.

THE CHAIRMAN: Are you content with that advice, Mr Miller?

MR MILLER: Frankly, I am not content with it, and it may be that we will have to pursue this in individual cases. I am not seeking to put in everything in the record. What I am seeking to do is to show you, when you are being asked now to draw a conclusion from something, that it is only fair you do so knowing what has gone in between. I am not going to waste time on this, but I say the idea that in front of the General Medical Council prosecution counsel is entitled to leave whatever or to tell you about whatever she wishes, is a strange one. If it is going to be fair – and Ms Smith believes that it is fair, she has said so – then if relevant entries, about which I may not be able to cross-examine because they do not involve the general practitioners, are being left out, then I have to stand up and ask her to draw your attention to them.

THE CHAIRMAN: I think the Legal Assessor also actually said that maybe in your opening you can actually redress that balance and if there are issues which are concerning you which Ms Smith has alluded to and you find those unfair, then you would be able to have the opportunity to redress that balance. That is my understanding from the Legal Assessor.

THE LEGAL ASSESSOR: There is certainly slightly more that needs to be corrected. Mr Miller said you were being asked to draw conclusions now. Insofar as Ms Smith may be doing that – I do not understand her to be doing that – that is not the purpose of an opening, and I advise the Panel here and now, publicly, they must not draw any conclusions until they have heard all the evidence and the submission of all counsel on the evidence. What they are being asked to do at this stage is to hear what the General Medical Council says will help them to draw conclusions to find the case proved at the end. They are not drawing conclusions now, they are having certain things identified to them. So Mr Miller is wrong to say that you are being asked to draw conclusions. I advise you, you are not to. You are having certain aspects of the case which support the contentions of the General Medical Council drawn to your attention at this stage.

THE CHAIRMAN: Are there any further points that you wish to make?

MR MILLER: There is nothing I can do. As I say, it happens particularly in this case that it may be necessary to ask Ms Smith to look at a particular document or ask you to look at a particular document which we say is relevant to the conclusion that she is going to seek for you to draw.

THE CHAIRMAN: Ms Smith, have you got any difficulties with the suggestion that has been made by Mr Miller?

MS SMITH: I do not undertake, in respect of any of these cases, to refer to every document that Mr Miller wants me to, but I am certainly, of course, happy to listen to anything that he says and I think perhaps it might be helpful if we have a conversation about it later on. For the moment I propose to go on with the course that I am.

I think that, in fairness to myself, in view of what he said about presentation to the GMC, I should make one point to this Committee. The defence are perfectly entitled not to give me any inkling of what their defence to the charges is, perfectly entitled, and they have availed themselves of that entitlement. I have not seen any expert report from any of them. They are perfectly entitled to that, I am not complaining, I am just telling you that I have not. They have seen detailed expert reports from the GMC in respect of every one of these children. I, therefore, have no idea at all what their defence is and in those circumstances it may be that the selection of some of the medical records which I would otherwise have made I have been absolutely unable to do. I do take issue with the suggestion that I am in some way being selective for any other reason than economy of time and in order, as we have already said, to tell you what the nature of the case against Professor Walker-Smith is. As I say, I am quite happy, of course, to talk to Mr Miller about various aspects of this later, and I think that is probably the best way. I cannot do anything on my feet. I shall proceed in the way that I am in relation to the way in which I open these patients, but at the end of the afternoon I will have some conversation with him.

THE CHAIRMAN: The only other way that I can actually think of is that maybe we can have a short adjournment now so that you can discuss these issues with Mr Miller and maybe the other counsel and we can resume the hearing in a short while.

MS SMITH: I am in Mr Miller’s hands, sir, because I think the problem is we may be able to deal with this one patient, but I am then going on to the next one and I do not know if the problem is going to arise again. If he would like to talk to me now of course I am perfectly happy for him to do so, or I can get on with the case and we can deal with it at the end of the afternoon. I am in his hands.

THE CHAIRMAN: Legal Assessor?

THE LEGAL ASSESSOR: I wonder if a way forward might be this. You are obviously not going to complete your opening this afternoon are you, Ms Smith?

MS SMITH: I am afraid I am not, no.

THE LEGAL ASSESSOR: There is some extra time tomorrow morning. Perhaps you will have finished dealing with the patients, or perhaps not, but insofar as there are outpatient record references that Mr Miller thinks in all fairness should have been referred to by you, could that perhaps be dealt with overnight and before the 11 o’clock start tomorrow, or 11.15 start tomorrow, so that you might extend your opening and you might go back over particular references so that the Panel can then make notes against the references to which you have referred now as part of your case, where they might find something that Mr Miller says is helpful in out patient records? Is that a possible way of doing it?

MR MILLER: I would certainly be content with that, sir.

THE CHAIRMAN: Is that acceptable to you, Ms Smith?

MS SMITH: I am certainly prepared to discuss it with Mr Miller as one method of going ahead. I do not guarantee that it will be the most effective.

THE CHAIRMAN: I fully appreciate that. Thank you, and for the time being you can now continue.

MS SMITH: Yes. I was going on to say to you that this is one of the cases where the colonoscopy was in fact carried out by Professor Murch. It indicated minor abnormalities of the vascular pattern in the rectum, multiple colonic lymphoid follicles in the caecum and lymphoid nodular hyperplasia in the terminal ileum. The histology report on the samples which was taken at colonoscopy indicated a mild patchy increase in inflammatory cells which was described as “could be in keeping with low grade quiescent inflammatory bowel disease.” An EEG and an associated investigation were then ordered by Dr Wakefield, although you will recall that one of the charges is that he had ordered an investigation although he had no paediatric qualification or clinical responsibility for this child.

Subsequently, a barium meal and follow through was carried out. The blood test results reported after the colonoscopy was carried out once again demonstrated normal inflammatory markers save that Child 2’s haemoglobin was noted to be slightly low. Thereafter, a lumbar puncture was performed, apparently on instructions from the gastroenterologist, without any neurological or psychiatric assessment. Professor Rutter, our psychiatric expert, is critical of that sequence of events, although he does accept, unlike some of the cases that you will be hearing about, that given Child 2’s very unusual history of regression, the actual decision to undertake a lumbar puncture was probably a reasonable one.

On the day after that, Child 2 was seen by the registrar in neurology and plans were made for him to see Dr Harvey. He was then seen by Dr Berelowitz for a psychiatrist assessment and Dr Berelowitz subsequent assessment sent to Dr Murch is at page 143 of the records. It is addressed in fact to Professor Murch, as I say, and he says:

“Thank you for asking me to see [Child 2] who I saw on the Ward on the 5th September 1996. I saw him at the request of yourself and Andy Wakefield, for the purposes of learning more about possible links between his presentation and measles vaccination and bowel disease, but it was not intended that I should have clinical child psychiatrist responsibility for him. I saw him together with his mother.”

He then sets out the history that was given by the mother in relation to his birth, the child’s birth.

“At the age of 13 months she said he had 25 words, but he gradually lost these words over the next 7 or 8 months. She thought he began to be a bit clumsy …”,

and the details in relation to that are set out. There is a description of the deterioration that she had perceived at the top of page 144.

“She has become confident that changes in diet affect his behaviour. She said that he had had diarrhoea from 20 months, largely unabated. He used to be very hyperactive, but when he went on a fine gold type diet, they discovered that wheat was causing him difficulties and the removal of certain foodstuffs from his diet led to improvement.

At the age of 5 he appeared very ill with considerable abdominal pain and mother became concerned about Vitamin B12 deficiency”.

Then there are the details of the treatment he was given in relation to that.

“In terms of diagnosis, she said he had been diagnosed as having a specific language disorder when he was under 4. This was clearly wrong. She said that at Harper House they said he was not autistic. He was reviewed by Harper House more recently and again she said the diagnosis was not of autism. He is about to see a metabolic specialist”.

There are details as to his family background.

“Mrs 2 reiterated that 2 started head-banging about 2 weeks after the MMR and hasn’t looked right since.

I observed 2 while talking to Mrs 2 and noticed that he had no eye contact and no language. He did not relate to people or objects in the expected way. He did not behave as though the other people in the room had minds of their own which were of interest to him.

I thought that the history and presentation were very typical of autism or a related disorder. Mrs 2 explained to me that she had previously had someone tell her that the problem was that she was unable to accept the diagnosis of autism. I explained to her that I was not going to attempt to do the same myself and was merely noting that his presentation looked like autism, whatever it actually turned out to be. I must say I thought the presentation was indeed very typical and await the next patient with considerable interest”.

That was a letter from Dr Berelowitz, the psychiatrist who was involved in this work. We say that letter is significant because it is further evidence of a research project, and it is also significant in relation to Dr Berelowitz’s ultimate diagnosis that Child 2’s condition was very typical of autism.

He was subsequently seen by Dr Harvey, who was the paediatric neurologist involved. On 16 September a discharge summary was sent to Child 2’s GP. It has just been pointed out to me that Dr Harvey is a neurologist, not a paediatric neurologist. On 16 September 1996 a discharge summary was sent to Child 2’s GP. In fact it is in the other volume. Could I ask you to go to the GP records of Child 2, page 140? Mr Miller is kindly pointing out that it is in the Royal Free records at page 145, if that is more helpful for you. That letter says,

“Child 2 was admitted to our ward on 2 September 1996 for further investigations of several problems. The main problems are of developmental regression from 20 months of age, diarrhoea from 20 months of age and abdominal pain from the same period.

Until 20 months of age mum noted that he had a normal developmental progress. He walked at 1 year and had started using recognisable words at 13 months of age. He was growing well and feeding himself. Mum does recount that at 13 months of age he had had his MMR immunisation and 2 weeks following this had started with head banging behaviour and screaming throughout the night. He subsequently seemed generally sickly. Nevertheless, the most major changes appear to have stemmed from the age of 20 months. At this time he started losing words. He apparently had a vocabulary of approximately 35 words at that time which he subsequently lost. He also became hyperactive. He stopped recognising people and did not appear to respond normally to them.

The diarrhoea started at this time, occurring 10 times a day and contained mucous. There was only episode where it contained blood. There was also at this time undigested food in the stool.

At 3 years he had sudden onset of weight loss associated with increased frequency of diarrhoea, general lethargy and pallor. There did not appear to be any precipitating events causing this and the episode as a whole lasted for 3 months. As it appeared to resolve it became apparent that he had lost several of his skills. Most specifically mum notes his interaction with other children. It is important to note that 3 such episodes of acute exacerbation with subsequent loss of developmental skills have characterised 2’s illness.

At 4 years of age he had the 2nd of these episodes again characterised by increased diarrhoea, lethargy, weight loss and loss of skills. Mum also notes at this time that he developed the odd puzzled facial appearance which he now manifests. At that time mum was concerned that food intolerance had a role to play and several food exclusions were tried. 2 appeared to make some response to exclusion of oranges, anything with preservatives and wheat. Specifically his diarrhoea appeared to reduce and he seemed to be calmer in himself.

By this time several reported diagnoses had been made, specifically that of a specific language disorder and also other suggestions of Aspergers syndrome”.

It then sets out the results from Dr Rolles, a paediatrician at Southampton, who assessed for a possible diagnosis of autism.

“An EEG at this time apparently showed the possibility of slow waves in the right temporal lobe. He had had this under anaesthesia and became unwell following this. Once again there was increased diarrhoea, decreased appetite, lethargy and he became increasingly withdrawn. At this time his mother became concerned that his symptoms may be related to aberrant B12 metabolism and he was tested for pernicious anaemia”.

I am trying to summarise this fairly so that I do not read every word to you.

“In summary, his present condition is characterised by odd episodes which occur roughly every 18 months…Mum also noted they can be associated with a jaundiced appearance and extremely pale stool. This obviously suggests some association with an obstructive jaundice”.

Then it goes into his birth details.

“Colonoscopy was performed under sedation. The rectum showed very minor abnormalities of vascular pattern without any frank ulceration or friability of the mucosa. Overall appearances were normal until the ascending colon. Here one definite apthoid ulcer was seen and towards the caecum there were multiple prominent colonic lymphoid follicles. The terminal ileum also appeared abnormal showing marked lymphonodular hyperplasia though there was no ulceration. Histology possibly demonstrates mild chronic inflammation within the lamina propria of the terminal ileum. It should be noted that it is difficult to estimate whether or not this is within normal limits. No granulomas were seen. Throughout the large bowel there was a patchy increase in chronic inflammatory cells with an occasional prominent lymphoid follicle with a germinal centre. There was also an occasional focus of acute cryptitis within the ascending colon. There was also mild crypt distortion…The patchy distribution of this inflammation and the involvement of the terminal ileum are in keeping with a diagnosis of Crohn’s disease”.

There is the result of a Schilling test, an MRI which did not show any structural abnormalities. The result of the Electrophysiology, an EEG, and a record of that was within normal limits though the frequency was a little low. Then you will see the blood tests and they are set out. After that there are the CFS tests, i.e. from the lumbar puncture, set out. There were urine tests, barium meal and follow through.

“Child 2 had a barium meal and follow through which was reported as being limited due to 2 having difficulty swallowing the barium but was normal”.

Then the plan,

“In view of the colonic inflammation it was decided to treat him with an enteral feeding regime using CT3211. This is a casein based formula with which we have had extremely good results in children with Crohn’s disease. It requires that he has CT3211 alone for 8 weeks. At this time we will consider re-introduction of food. We will review him regularly throughout this period and subsequently to assess his progress.

With regard to 2’s neurological problems an opinion of a neurologist and a child psychiatrist have also been sought. I am sure that they will forward further information to you. We will review 2 in clinic in 2 weeks time”.

Because he was on an enteral feeding regime, he would require a repeat colonoscopy having been on the diet for eight weeks. That was the standard necessary colonoscopy as a result of the enteral feeding regime.

THE CHAIRMAN: Just for the press, a couple of times the first name of the child came out. Can you please make sure that the child’s name is not put into the description.

MS SMITH: Perhaps I can just say at that point, because it did not occur to me when Mr Miller made the point he has, but if it reassures him, at least for the rest of the afternoon, I am reminded that I said to you that I was proposing to refer to the GP letter. I am also going to refer to the discharge summaries in relation to these children which set out the history of the symptoms they have, and indeed set out the gastrointestinal symptoms in relation to this child. That was the course that I proposed to take throughout, so I am certainly not, not dealing with the clinical details. It is simply that I am dealing with them in printed letters where I can do so, rather than in handwritten notes.

That was the discharge summary, and that letter, we say, indicates that this child had indeed all the investigations which were included, ultimately, in Project 172-96. As you have heard, a tentative diagnosis of Crohn’s disease was made. Enteral feeding was started with a further colonoscopy planned. In order to carry out that follow-up colonoscopy, Child 2 was admitted again to the Royal Free under Professor Walker-Smith’s care in November 1996, when he was still on enteral feeding, having a liquid diet, and he was noted to be currently well and active. On this occasion the colonoscopy reported normal findings. Professor Walker-Smith’s letter to the paediatric neurologist who had previously been involved, is in the Royal Free records at page 140:

“Further to my earlier letter in which I just mentioned 2. In more detail, we investigated 2 for evidence of Crohn’s disease. I had been, as you may remember, somewhat reluctant to do this in 1995 but more recently in view of Mrs 2’s concern that his gastrointestinal symptoms and his general symptoms may be related to MMR, we went ahead and did a colonoscopy. This in fact did show evidence of bowel inflammation with involvement of both the ileum and the colon and we commenced him on enteral nutrition. In fact, rather surprisingly, there has been quite a considerable improvement in his general behaviour and the repeat colonoscopy which was undertaken this week showed return to endoscopic normality although at the time of writing I have not had the histology report. I will ask my Registrar to send you a full discharge summary after this current admission”.

That is the full discharge summary by Dr Casson I have just referred you to. Child 2 continued to have a very complex picture, both behaviourally and gastrointestinally with suggestions of improvements on some occasions with both. In February 1997 he was prescribed sulphasalazine, an anti-inflammatory. Constipation then became a major problem and attempts to obtain some sort of objective assessment of his behavioural problems was undertaken without any very clear results.

In so far as the charges are concerned, there are firstly the general charges relating to Dr Wakefield, Professor Walker-Smith and Professor Murch, that this child had investigations for research purposes without Ethics Committee approval for such research. That research was clearly, the charges say, pursuant to Project 172-96 and yet the child had been enrolled before 18 December 1996, which you will recall was the express start date given ultimately by the Research Ethics Committee. Child 2 had not been vaccinated with either the measles or the MR vaccine, but with MMR. The proper research consent forms and patient information sheets were never filed with his records, as the Ethics Committee specifies.

There are additional charges to those charges in respect of all three doctors. In respect of Dr Wakefield, first with regard to his responsibility for causing Child 2 to undergo a lumbar puncture without having him properly neurologically or psychiatrically assessed; secondly, for ordering investigations -- you will recall this was the EEG – without having paediatric qualifications and in contravention of the limitations of his honorary consultant appointment.

In addition, there are charges against Professor Walker-Smith for causing Child 2 to have a colonoscopy and a barium meal and follow through which were not clinically indicated, and for doing this contrary to his later representation to the Ethics Committee that all the investigations were clinically indicated. He is also charged with causing Child 2 to have a lumbar puncture without any prior neurological or psychiatric assessment.

Lastly, there are additional charges in respect of Professor Murch with regard to his role in carrying out the colonoscopy on Child 2. The main decision, it is our case, that the child should undergo that procedure was undoubtedly that of Professor Walker-Smith, but it is our case, on the basis of our expert evidence, that as the consultant who actually performed it, Professor Murch had a responsibility to act himself in the best interests of the child, himself to be aware of the child’s clinical history and symptoms, and he should not himself have carried out the procedure if he did not believe that it was clinically indicated, regardless of the request coming from his colleague Professor Walker-Smith.

Sir, that is all I have to say in regard to Child 2, who is the first child, and I am now going on to Child 1, who is the second child. It is probably helpful, although you are not going to be needing them for a little while, if you extract the GP records and the Royal Free records for Child 1 and put away those for Child 2.

Child 1, again a little boy, who was born in January 1993, and was referred ultimately to the Royal Free Hospital in May 1996, when he was nearly three and a half years old. As far as his background, in summary, is concerned: prior to his arrival at the Royal Free the GP records note him to be developing normally when he was a baby, although before he was a year old his mother was expressing some concerns to the general practitioner about his hearing. He had the MMR vaccination in January 1994. By the time of his 21 month check in 1994 he was recorded as not understanding or expressing speech very much, and a couple of months later, when he was two, as having only seven or eight words and not being able to understand simple commands.

In February 1995 his parents said that he had lost the words that he had developed; he had only three meaningful words; his comprehension was delayed, and it was noted in this context that his older brother had some developmental problems. The GP records describe him as autistic for the first time in November 1995, so that is just before he was three. He was seen by a consultant psychiatrist in March 1995, that was Dr Hauck, and in an undated letter Child 1’s mother wrote to Child 1’s GP requesting a referral to Professor Walker-Smith and her GP, Dr Barrow, who will be giving evidence, will tell you that he was aware by then that the mother had strong views that MMR vaccination had played some part in her son’s difficulties.

If you look at the GP records for Child 1 at page 125 you will see the letter that was sent. Dr Haughton is another GP in the practice, you are going to be hearing from the GP who was ultimately responsible, who is Dr Barrow:

“Dear Dr Haughton,

I would like you to refer my son [Child 1] to the below address immediately …”

I cannot read the end of this, you can see it is missing, but it says:

“… a severe metabolic disorder needs tests done …”

Then it gives the address at the Royal Free.

Dr Barrow will say that the term “severe metabolic disorder” would not have come from him, but in any event that is what the mother was requesting the referral in relation to, and he referred Child 1 to Professor Walker-Smith, and if you go to the Royal Free records, at page 57. You will see the letter:

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

[Child 1] initially developed normally, reaching the normal milestones until he was about 15 months old. He then regressed and has now been diagnosed as autistic; his elder brother … is also autistic.

Mr and Mrs [1’s] most recent concern is that the MMR vaccination given to their son may be responsible for the autism.

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

I would value your opinion regarding this challenging family.”

That is from Dr Barrow, who, as I say, you will be hearing from. It is our case that that letter is significant for a number of reasons. It appears that the parents had already been in contact with Professor Walker-Smith. The diagnosis at that stage was one of autism, albeit with a suggestion of regression. There was apparently a family history of autism, and significantly there is in that letter no mention of gastrointestinal symptoms and the referral was prompted by the parental concern that his MMR vaccination might be responsible for his autism, i.e. it is our case that it was plainly in pursuit of research into that issue which resulted in his being seen by Professor Walker-Smith.

At outpatient appointment was arranged by Professor Walker-Smith in June 1996, and there was a clinical history taken by Professor Walker-Smith which did indeed include gastrointestinal symptoms of undigested food, no control, occasional blood in the stools, and Professor Walker-Smith concluded that the child had the features of a syndrome known as “toddler’s diarrhoea” and that is a well-recognised medical syndrome which affects small children, which does not normally require treatment and normally goes away by the time the child is five or six.

If you turn to page 54 of the Royal Free records you will see Professor Walker-Smith’s conclusions and plan:

“Dear Dr Barrow,

Many thanks for referring [Child 1] with autism. It is difficult to associate a clear historical link with the MMR and the answer to autism although [Mrs 1] does believe that [Child 1] had an illness 7-10 days after MMR when he was pale, ? fever, ? delirious, but wasn’t actually seen by a doctor. Between the age of 1 year and 18 months his development slowed and then deteriorated. It is very interesting that he has a 5 year old brother who also has been diagnosed as part of the autistic continuum. As part of Dr Wakefield’s and mine interest in the relationship between immunisation and chronic inflammatory bowel disease, I have arranged for routine blood tests to be done for screening for C-reactive protein, etc. The diarrhoea which [Child 1] currently has does have the features of toddler’s diarrhoea. His mother is concerned by the diarrhoea. Loperamide in a dose of 2mgs twice a day could be tried therapeutically. She was concerned that this could have had an adverse effect on his neurological development, I am not aware of Loperamide ever having such effects, its only side effects that I am aware of is some abdominal pain and skin rashes occasionally and in children with intestinal obstruction with overdosage you can get paralytic ileus. However, I think it is an option to be kept available is the diarrhoea causes concern.

May plan would be to see him again in 3 months time and then if [Mrs 1] feels that it is appropriate we could consider performing endoscopy and further assessments neurologically and psychologically of his autism to explore the possible link between measles immunisation, bowel inflammation and autism.”

Again we say that letter is significant for a number of reasons. We are going to be calling expert evidence that the results of the blood tests were normal, i.e. that there were no inflammatory indices which could have been suggestive of inflammatory bowel disease.

You will note that there was a clear plan to review in three months. There is, we say, an emphasis placed on parental decision as to whether the child should then undergo endoscopy, and the apparent reasons to go ahead, we say, i.e. on the terms of that letter to explore the possible role of immunisation, would be in clear pursuit of a research programme, particularly, it is our case, given the diagnosis of toddler’s diarrhoea which Professor Walker-Smith had made.

After that letter was written Professor Walker-Smith then has a communication with Dr Wakefield, and that is at page 53:

“I saw this interesting child with autism which began some weeks following MMR although there was 7-10 days after the MMR at the age of 1 a brief illness during which he was pale, possibly had fever and his mother said he may have been delirious. [Mrs 1] was keen that you would have a look at a document that she has got concerning homeopathic remedies and I am passing this on to you.”

So that was the next step in the correspondence.

Subsequent to that, not three months later as was planned but one month later, on 21 July 1996, Child 1 was admitted to hospital. The clerking note on admission says: “Referred for the work up of ? relationship between autism, measles and IBD”.

It is our case again, on the basis of our expert evidence, that there were no clinical indications for colonoscopy; this child, as I have pointed out to you, was not referred by his GP for gastrointestinal symptoms. Professor Walker-Smith did elicit gastrointestinal symptoms, as I have read to you, in outpatients, and he himself attributed those symptoms to toddler’s diarrhoea. He took blood tests. The inflammatory indices were normal. There was thus, we say, no gastrointestinal reason to investigate.

Professor Booth further criticises the apparent reliance on the views of the mother in taking the decision to colonoscope. Again, as I have already pointed out, the patient is the child. Of course the parents’ views are extremely important, but the responsible paediatrician, we say, has to bear in mind that with a sick child parents are utterly understandably desperate for answers and sometimes they lose objectivity. So it is our case that the doctor has a responsibility to think through that situation, and in this case, as I say, the correspondence indicates a reliance on the mother’s view as to whether endoscopy was appropriate.

It is also the case that no psychiatric assessment as to the nature of the behavioural disorder that this child was suffering from was made before invasive procedures were embarked upon. After he was admitted consents were obtained, one was for colonoscopy on a standard form for a clinical procedure and that is the same form as the one I referred you to in relation to the previous child. There was another consent form, which you should see because again it comes up in the records a great many times, which was a consent form for general research biopsies, and that is at page 42. That is a consent form which is given to parents whose children have been referred for clinically-indicated diagnostic colonoscopy, and during that procedure permission is sought to take some extra biopsies for laboratory research. That is not a research consent to project 17296. It is a general form asking for permission to retain extra samples from a standard procedure, and you will hear from Dr Pegg that it was common practice at that time to retain tissue samples from all patients who came in for an investigation and those tissue samples were retained for general research. So, as I say, that is not the research consent form, and, indeed, it is not in the same terms as the consent form which would have been appropriate had consent been requested for a research colonoscopy.

On the day after Child 1’s admission an attempt was made at colonoscopy. This is one of the cases where the procedure was carried out by Professor Murch, and the procedure had to be abandoned because of gross faecal overloading, which meant that the colonoscope could not be inserted properly, or, indeed, obtain a clear view. A plan was therefore made to give Child 1 a bowel clear-out and repeat the procedure. Our expert, Professor Booth, again criticises the decision to repeat the colonoscopy when all the signs at that stage were of very significant constipation.

The next day, which was 23 July, an EEG was carried out and blood tests were reported as again showing normal inflammatory indices. The day after that, 24 July, an MRI scan was carried out. The next day consent was taken again for colonoscopy, again in a standard form for a clinical procedure. Consent was also taken for general research biopsies, and Professor Murch again undertook the colonoscopy having not done it the first time. The record of his findings is, “Some evidence of scope trauma in the descending colon”, in other words a very minor injury caused to the tissue by the passage of the colonoscope itself, and the rest of the record was, “No obvious pathology”, but he indicated that because of the presence of good debris he had not been able to enter the terminal ilea.

The colonic histology report on the biopsies taken by Professor Murch when he did the colonoscopy refer to focal active chronic inflammation in the caecum, and prior to Child 1 being discharged there was a letter from Dr Casson to Dr Wakefield (page 52 if you need to refer to it) simply saying:

“When would you like us to review this patient again and are there any other procedures we should be performing?”

We say, again, this letter is significant in that it makes clear that follow-up, review and investigations were research-driven.

I am now going to turn to the discharge summary which again will be quite a long detailed document, so if you wanted to break for a short time this would be the moment, unless I go on to the end of this child, but that will be a little while.

THE CHAIRMAN: I think it will probably be appropriate to have a break now. We will have a break for 20 minutes and resume at 4 o'clock.

(Short adjournment)

THE CHAIRMAN: Ms Smith.

MS SMITH: Thank you, sir. I was just about to take you to the discharge summary in respect of Child 1, which is at page 49 of the Royal Free Hospital records. It is a letter to the GP.

“[Child 1] was admitted for further investigation of his autism and specifically to look into a possible association between his neurological condition and any gastro-intestinal disorders. The main problems are a ‘classical’ autism diagnosed 1 year ago, and of diarrhoea. He was born following a normal pregnancy”,

and it goes into the details in relation to that.

“[1]’s developmental problems were first noted when he was 18 months. At this time his brother was being investigated for autism. Mum noted that until 1 year of age, [1] appeared very bright and apparently had 5 full words. He also walked at 14 months ….. Subsequently he had apparently lost his vocabulary. According to mum he has not progressed normally since then, especially with speech and comprehension. There was no recall of his various social milestones.

As regards present development he has just started, once again, to say recognisable words.”

Then it goes into the physical abilities and emotional status.

“His diarrhoea started approximately 18 months ago. He passes 5 watery stools a day which contain no blood or mucous. They do contain some undigested food. He appears to have no control over his bowel motions and frequency is increasing. His appetite has always been poor and there has been no obvious change in this. He has only very occasional episodes of vomiting …..

He is up to date with his immunisations including his MMR at 12 months of age. There is obvious parental concern that this has some bearing on his subsequent condition. He is at present on no medication.”

It sets out his family history, and notes that there is a brother with a speech problem also described as being part of the autistic continuum. It then says:

“He also has Toddler’s diarrhoea.

On examination he is obviously extremely active though there was no obvious abnormality to find …..

An initial colonoscopy was attempted on the 22nd July, however this had to be abandoned due to gross faecal loading. He was subsequently cleared out and the procedure was repeated 3 days later. On this occasion, the caecum was reached although it was impossible to pass further due once again to accumulated faecal matter. Macroscopically there was no abnormality noted ….. upper endoscopy was also performed. There was no obvious lesion to the 2nd part of the duodenum. A small amount of altered blood was noted.

Histological examination of the biopsies taken demonstrated a small degree of focal active and chronic inflammation within the caecum. Biopsies of the ascending colon, sigmoid and rectum were all normal. The small bowel series demonstrated occasional foci of chronic inflammatory cells within the lamina propria of the gastric body. No active inflammation was seen. No helicobacter were seen. Further biopsies from the oesophagus were reported as normal. Samples [taken] ….. awaiting these results.

A brain MRI was performed.”

A slightly increased signal in one area, no other abnormality, and that one was thought not likely to be significant.

“We would like to review [1] in clinic to discuss the implication of the mild degree of inflammation seen in his biopsies. It is also not entirely clear whether his neurological condition in fact represents a neurological deterioration in view of lost milestones, or whether it is a classical autistic picture.

We will consider these features when we see him again.”

That was signed from Dr Casson. Three weeks after that letter Professor Walker-Smith wrote to the GP saying he had spoken to Child 1’s mother and suggested a therapeutic trial of sulphasalazine, which is an anti-inflammatory in the form of a salazopryin syrup, although he noted that the blood tests which might have indicated significant inflammation were in fact normal. He concluded that he did not plan to see Child 1 again, although Dr Wakefield would be assessing the research aspects of the problem.

On 3 October 1996, so that is some two months after his first admission, Dr Casson wrote directly to Child 1’s mother confirming a further admission on 23 October for barium meal and follow-through, EEG and lumbar puncture, all to be performed under sedation. Child 1 was duly admitted and underwent a barium meal and follow-through, which were recorded as being very difficult to perform because of his behavioural difficulties, but which indicated marked faecal loading and a conclusion that the small bowel was normal. In this case, unlike some you will be examining, Dr Harvey, the consultant neurologist who was named, you will recall, as responsible for the neurological assessment, appears to have seen Child 1 and made an assessment, albeit not a full one. A standard clinical consent form for lumbar puncture was then signed and a lumbar puncture was carried out. Since a neurological opinion had been sought prior to that procedure being carried out, we do not in this case criticise that investigation. The next day another clinical consent form for another colonoscopy was obtained, and this was needed because the terminal ileum had not been reached due to the marked constipation. In fact, although there was a consent form, it appears that Child 1 never had that repeat colonoscopy, and in the discharge summary on that occasion he was prescribed liquid paraffin for his constipation.

Subsequently, he had an outpatient consultation with Professor Walker-Smith, and the outcome of that was recorded in Professor Walker-Smith’s letter to the GP, which is in the Royal Free records at page 39:

“I reviewed [1] again in the outpatients. There has been some improvement with Salazopyrin however, [his] mother has not really given it very long she was concerned at one stage that Salazopyrin might have produced a rash. I think it is most unlikely that the rash she demonstrated is anything to do with Salazopyrin. At present he is taking ….. Paraffin” – so that is for the constipation – “10ml a day and Salazopyrin” – which is an anti-inflammatory – “I recommend continuing this for the moment.

I have made no definite appointment to see him again. I would recommend continuing on this medication as we have found other children who have had this kind of colitis have responded well to this therapeutic approach. Mrs [1] also raised the question of whether we should investigate the brother ….. I think it might be appropriate to do this in due course, although his gastro-intestinal symptoms don’t appear to be very severe.

Please do not hesitate to contact me if you have any queries regarding this child.”

Subsequently there were outpatient appointments with Professor Walker-Smith which recorded some improvement, although he continued to have gastrointestinal symptoms. On 15 July 1998 Professor Walker-Smith wrote to the GP, and you will see that at page 38:

“I saw [1] again at mother’s request.”

Then it sets out that the mother was keen to see how well his constipation had responded to a treatment that had been prescribed by another doctor. Professor Walker-Smith says:

“Mrs [1] was very keen that I should see the child in order that I [could] pursue some of the research activities suggested by Dr Flint. In particular the role of aluminium, trace metals ….. This is certainly not in our area of expertise and I have told Mrs [1] that really we are not able to help her further with the care of [1] and accordingly I have not arranged another outpatient appointment to see him.”

We say that letter again rather supports a lack of clinical involvement, in the sense that by that stage it refers to continuing symptoms, but an indication that as far as the Royal Free Hospital is concerned they were not able to help any further.

The GP then turned back to the consultant paediatrician Dr Rolles at Southampton Hospital, who in turn wrote to Dr Wakefield, and that is in the GP records at page 64. I am not going to read that letter out in its entirety, but you will see that it is a letter from Dr Rolles, Consultant Paediatrician, to Dr Wakefield, saying “You know [1] and her sons very well”, and saying he is trying hard to maintain contact with them, and you will see what it has to say in the second paragraph, that Mrs 1 was concerned as to the reason why investigations in respect of the two were not proceeding at the Royal Free. Dr Rolles makes the point that he is simply repeating what Mrs 1 thinks. He concludes:

“I am sorry to trouble you over this matter but I do feel that if at least I could have a response from you it will help me as I try to support this lady who is very much absorbed in trying to unravel, in her own way, the complexity of her children’s problems.”

There is not a response to that letter apparent in the records. I am referring to it for the sake of completeness to give you an overall picture. It takes us up to 1999. I will ask the GP to complete the story insofar as it assists anyone. Like many of these children, Child 1’s problems appear thereafter to continue. They appear in this case to be mainly constipation and behavioural problems within the autistic spectrum. That concludes the role that was played by these doctors in the child’s care.

Professor Rutter’s and Professor Booth’s criticisms are reflected in the charges. Again, firstly, there are general charges relating to all three doctors that this child had investigations for research purposes with ethics committee approval for that research. Again, we say that research was clearly the research pursuant to Project 172-96, but the child was enrolled before 18 December. This child was never vaccinated with measles or measles/rubella vaccination. There is no evidence we say anywhere that he suffered from disintegrative disorder as opposed to a possibly, and only possibly, regressive form of autism, and indeed we criticise the fact that no attempt was made to ascertain the nature of behavioural disorder prior to embarking on an invasive colonoscopy. The proper research consent forms and patient information sheets were never filed with the records, as the Ethics Committee had specified.

In addition, there are charges in respect of Professor Walker-Smith for causing an attempted colonoscopy which was not clinically indicated, and a repeat colonoscopy and barium meal and follow-through which were contraindicated, because the failure of the first colonoscopy was clearly owing to constipation, suggesting, we say on the basis of our expert evidence, that any symptoms he did have were caused by that constipation, and anyway in the presence of reasons which did not clinically indicate a colonoscopy to be carried out.

In addition, Professor Walker-Smith is charged with what we say, again on the basis of our expert evidence, was an inappropriate reliance on the parental views, and, in the light of that, acting contrary to what should have been paramount for him, namely the best clinical interests of his patient Child 1.

Professor Murch is charged, in addition to the general charges they all face, which I have just referred you to, with charges again arising out of his role as the person who carried out the colonoscopy. Again, we say the initial decision that the child should undergo that procedure was Professor Walker-Smith’s, but, as in the case of Child 2, who I have already dealt with, it is our case that, as the consultant who actually carries out the procedure, Professor Murch has his own responsibility to make himself aware of the child’s clinical history and presenting symptoms, and he too should not have done that procedure in circumstances where it was not clinically indicated or in the best interests of Child 1.

So those are the charges relating to that child.

I am now going to go on to Child 3, and it is probably helpful if you put away the records for this child and extract the ones for Child 3 – just the GP and the Royal Free Hospital records.

This was a boy again, born in January 1990, and referred to the Royal Free Hospital in 1996, when he was six years old. His brief background was that he had his MMR vaccination when he was fifteen months old.

The first concerns recorded in the GP records arose in June 1992, when he was 2½. His parents sought advice as to his hearing because his speech appeared very delayed. By October 1992 it was felt that he had a behavioural disorder of some kind and he was seen at the Alder Hey Children’s hospital in Liverpool, his local children’s hospital, by a consultant psychiatrist originally and then by a consultant paediatric neurologist called Dr Rosenbloome. The view expressed at that time was that he was probably autistic and that he was to be kept under review by the Alder Hey Hospital.

In February 1993 the consultant paediatric neurologist, Dr Rosenbloome, arranged for Child 3’s admissions for investigations at the Alder Hey Hospital and he had a CT brain scan, an EEG and blood tests, all of which were thought by that hospital to be normal. He came under the care of the child development centre there and underwent a formal autism assessment, which resulted in a diagnosis of autism and severe mental delay.

In August 1994 the parents raised with Dr Rosenbloome the possibility of a link between his condition and his MMR vaccination and Dr Rosenbloome at the Alder Hey arranged for an MRI of Child 3’s brain to be carried out. That was performed under general anaesthetic and there were at that stage, in the view of that hospital, no definite abnormalities identified. But, his behavioural problems continued and as well as continuing under Dr Rosenbloome’s care he was referred to an educational psychologist. Gastrointestinally, as far as the GP records are concerned the only difficulties appear to be occasional references to severe constipation.

On 19 February 1996 Child 3’s GP, Dr Shantha, wrote to Professor Walker-Smith referring Child 3, and the letter is in the Royal Free Hospital records at page 38.

“Dear Professor Walker-Smith



Thank you for asking to see this young boy who developed behavioural problems of autistic nature, severe constipation and learning difficulties after MMR vaccination. The batch incriminated was D1433, incidentally, which was the discontinued batch following adverse reactions.

He has seen Dr Oppenheim [that is the child psychiatrist] at Alder Hey Hospital and Dr Rosenbloome at the same hospital.

He is attending special school. His severe constipation is requiring frequent enemas and oral medication.

The parents are very convinced that the difficulties in his behaviour etc. started only after the vaccination.

I am extremely grateful for you to have taken on [Child 3] for case study.

Your sincerely

Dr A.L. Shantha.”

Dr Shantha, who will be giving evidence, cannot now recall the circumstances regarding that letter or how she became aware that Professor Walker-Smith wanted to see the child.

As a result of her letter, Professor Walker-Smith did indeed see the child in outpatients on 3 April 1996, and subsequently wrote to Dr Shantha in a letter dated
4 April 1996, which is in the Royal Free records at page 39.

“Many thanks for referring this child. As you say there is a clear history of the child being completely well until the age of 14 months when he had MMR. On the second day after the injection he developed a fever and a rash and since then his mother noticed dramatic change in his behaviour. He has also been investigated in Alder Hey Hospital. Recently his mother has been told by Social Services that it is likely that the MMR might have caused the problem, had been in touch with the organisation JABS who had mentioned the research that Dr Andy Wakefield has done at this hospital into the role of MMR vaccination and Crohn’s disease, hence my interest. We have now seen a number of children who have had features of both Crohn’s disease and autistic behaviour following MMR. Whether this is causally related I simply don’t know at present. [Mrs 3] is keen that we pursue this avenue. In the first instance I have screened [Child 3] with routine blood tests etc. and we will consider in due course whether it is appropriate to go ahead and perform a colonoscopy. A colonoscopy offers the opportunity to demonstrate if there is any ongoing infection in the gastrointestinal tract which could be in some way cause related to his present problems.

Many thanks for referring this interesting child.”

With regard to that letter, Dr Shantha in fact takes issue with Professor Walker-Smith in his interpretation of her letter because he says:

“As you say there is a clear history of the child being completely well until the age of 14 months when he had MMR”,

and Dr Shantha’s evidence will be that she was reporting the parents’ account, not her own.

The letter clarifies the reasons why the referral was being requested. Professor Walker-Smith highlights his interest in Crohn’s disease, that is inflammatory bowel disease, but it is our case on the basis of our expert evidence that the gastrointestinal symptoms, which were constipation, sometimes with blood, that this child had were not symptoms normally associated with Crohn’s disease.

At that stage Professor Walker-Smith was seemingly contemplating what we indeed say would have been the proper course, namely blood tests prior to performing colonoscopy to test for inflammation. But, he then, if you look further into the letter, appears to be suggesting that the reason he was in fact contemplating colonoscopy was so that samples could be obtained for the testing for infection. We say that that was a clear research purpose.

Professor Walker-Smith then wrote to Dr Wakefield and the letter is on page 40. Indeed, it echoes what has been said to the GP:

“There is a clear history of this child having been perfectly well until the age of 14 months, and then the second day after the MMR injection there was a change in behaviour which has persisted thereafter and he has been diagnosed of having behavioural problems of autistic nature.

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

So we say despite, apparently, no new information, Professor Walker-Smith appears to have reached the decision that the colonoscopy which originally he was considering now was awaiting the full working out of the research protocol.

Professor Walker-Smith wrote to Dr Rosenbloome on that day and that letter is at page 53. Dr Rosenbloome, you will remember, is the paediatric neurologist at the Alder Hey Hospital:

“This child was referred to me by his GP because of the work of my colleague Dr Andy Wakefield at this hospital concerning the role of MMR in the genesis of Crohn’s disease and more recently possibly in relationship to the association with autistic behaviour. We have seen several children who have had both features of Crohn’s disease and autistic behaviour related to MMR vaccination. I have therefore seen the child in the clinic. I would be most grateful if I could have a report of your diagnosis and previous investigations and particularly his views concerning his autistic behaviour.”

Then on 17 July Child 3 attended another outpatients’ appointment with Professor Walker-Smith. That does record gastrointestinal symptoms, and they were constipation. Professor Walker-Smith wrote to the GP the next day, 18 July 1996, and that is the letter at page 52. That refers to the blood tests that he had taken:

“Initial screening tests for [Child 3] for inflammatory bowel disease were negative. However we are arranging for [Child 3] to be admitted on Sunday the 8th September for colonoscopy followed by a period of investigation in the ward. We will let you know the results of these investigations in due course.”

On the same day he wrote to Dr Wakefield at page 49:

“This child with autism has had no evidence of bowel inflammation on routine blood tests, however we are arranging his admission for colonoscopy on Sunday the 8th September, followed by your intensive investigations. I would be very grateful if you could arrange then other aspects of his admission.”

He also wrote again to Dr Rosenbloome, and that is on page 50:

“Thank you so much for sending the notes of [Child 3]. We are arranging his admission for Sunday the 8th September for colonoscopy, however the initial blood screens for bowel inflammation were negative, however Dr Wakefield is of the opinion that subtle changes in relation to inflammation may be present in such children, and we have arranged [Child 3’s] admission for a week to 10 days for a period of intensive investigation. We will let you know the results in due course and return his hospital notes to you then.”

So we say a clear, clear plan to give this child a colonoscopy in the absence of any of the usual clinical indications for colonoscopy, and apparently to further the theory that was held by Dr Wakefield that if an investigation was carried out, something might be found. We say that that is clear evidence of a research motive.

Consents were obtained for the colonoscopy, again on the standard clinical consent form and a further research biopsy standard consent form. Colonoscopy on this occasion was carried out by a Dr Thompson, who was Professor Murch’s junior colleague, and the report was normal to terminal ileum but with increase to the number of lymphoid follicles in the terminal ileum. The histology report on the samples removed at colonoscopy noted mild inflammatory and reactive changes of uncertain significance.

Over the next few days Child 3 had an EEG, an MRI, a lumbar puncture and a barium meal and follow through. All those investigations were carried out without any apparent attempt at a neurological or psychiatric assessment at any time with this child, let alone prior to the carrying out of those tests. A discharge letter was sent on 31 October 1996 and if you refer to page 26 you can see the details of that:

“[Child 3] was admitted for investigation of possible inflammatory bowel disease and a possible association of this with autism.”

It then sets out his birth history:

“He had his MMR injection at 13 months of age and on the 2nd day after injection he had a fever and a rash. Overall mum considers that his developmental regression has progressed since this time.

As regards bowel symptoms, he intermittently suffers from quite marked constipation. He has had occasional rectal bleeding although this does seem to accompany passage of a hard stool.”

Then there is family history, and:

“Colonoscopy was performed under sedation. This was reported as normal to the terminal ileum but with increase in the number of lymphoid follicles within the terminal ileum. An upper endoscopy was also performed on this occasion and was reported as normal.

HISTOLOGY

Small bowel mucosa showed an increase in intra-epithelial lymphocytes but there were no architectural abnormalities. Histology of the terminal ileum showed prominent lymphoid follicles. Colonic histology was all reported as within histological limits. Overall there appeared to be therefore mild inflammatory reactive changes in the small bowel samples …”.

Then the results of the blood tests are set out and on the next page the cerebrospinal fluid from the lumbar puncture results are set out. Then:

“Barium meal and follow through small bowel was normal with no evidence of inflammatory bowel disease. The terminal ileum was well visualised and appeared normal.

MRI SCAN OF BRAIN

… normal. There was a small patch of altered signal in the left frontal area. There was no evidence of further abnormality …

EEG

This was within normal limits. Unfortunately it was impossible to perform evoked responses.

Therefore he does not appear to have significant bowel disease. There are several mildly aberrant blood results specifically an elevated blood lead and an elevated lactate. No other metabolic abnormalities were detected. The significance of the MRI findings are uncertain.

We will have to re-consider these findings when we review him again in clinic. As regards the protocol that patients who are being investigated as [Child 3] is concerned, we have been unable to perform the Schilling test and the evoked potentials.”

So that is the discharge letter.

Subsequently, in December 1996 Professor Walker-Smith wrote again to the GP and that letter, again in the Royal Free records, is at page 25. He said:

“You remember you kindly referred [Child 3] to me and we sent a discharge summary to you on the 4th October. Further critical analysis of histology results has led to an amendment to the discharge summary which I am now enclosing. Our final diagnosis is of indeterminate ileo-colitis with lymphoidnodular hyperplasia and we had no adequate explanation for his elevated blood lead or elevated lactate level. We sent him home on liquid paraffin”,

which is the treatment for constipation.

“Since then I have not heard anything further concerning him …”,

and then there is reference to another outpatients’ appointment.

“I have not seen him since discharge, I would be interested to hear concerning his progress. In the light of these histological findings and if gastrointestinal symptoms persist, treatment with a drug such as Asacol (Mesalazine) might be of some therapeutic value. I look forward to hearing any comments that you may have.”

An amended discharge letter was enclosed in the notes which makes that change on the basis of the further critical analysis that had been carried out to indetermined ileo-colitis with lymphoidnodular hyperplasia. In fact, Child 3 was indeed given anti-inflammatories. He remained on those and with treatment of constipation, but the overwhelming complaint was symptoms attributable to the latter, to constipation, and sadly his severe behavioural problems continued, attributed to his mental retardation with autistic features.

Insofar as the charges are concerned, Dr Wakefield, Professor Walker-Smith and Professor Murch are all charged generally arising out of their duties as responsible consultants, that these children had investigations for research purposes without ethics committee approval. Again, the child was enrolled before 18 December, the start date given by the Research Ethics Committee. Child 3 was never vaccinated for measles or measles/rubella vaccination. There is no evidence, we say, that he suffered from disintegrative disorder, the condition said to be, you will recall, the subject of project 17296. His history prior to admission was of mental retardation with autistic features and no attempt was made for him to undergo a psychiatric or neurological assessment prior to submitting him to having invasive tests, both colonoscopy and lumbar puncture. The proper consent form and patient information sheets were not filed with his records.

In addition to those general charges, there are additional charges in respect of Dr Wakefield of causing Child 3 to undergo a lumbar puncture which was not clinically indicated, and was contrary to the child’s interests, and doing so in circumstances where he had expressly told the ethics committee that the tests were clinically indicated.

There are additional charges in respect of Professor Walker-Smith in the same terms as to causing Child 3 to have a lumbar puncture. In addition he is also charged with causing the child to have a colonoscopy, barium meal and follow through, which were not, we say, in the presence of constipation and in the absence of any indication of inflammation, investigations which were clinically indicated. He is further charged again that he does this in circumstances where he expressly tells the Ethics Committee that the tests that he is performing are clinically indicated.

Sir, that is Child 3. I note the time and I am in your hands whether or not you wish to embark on the next child.

THE CHAIRMAN: No. I think it is time that we should rise. There has been a lot of information provided to the Panel which it does take time to absorb, and also to keep the concentration going as well. So I think that this would be the time to rise and we will resume tomorrow morning. Tomorrow we are starting late, between 11 and quarter past 11. Of course, I do appreciate that Mr Miller has certain points he wishes to discuss with you, and maybe you can come to some kind of arrangement or agreement by tomorrow morning.

MS SMITH: I am sure we can all use the time very usefully, sir.

THE CHAIRMAN: We will have a shorter lunch break, if that is acceptable to you, of about 45 minutes, and we will sit until five o’clock. We will now rise and resume the hearing at between 11 and quarter past 11 tomorrow.

MS SMITH: Sir, can I raise one matter quickly in general terms in relation to the witnesses? You will appreciate that there have been unavoidable delays and, as a result of that, we are having to do a great deal of re-arrangement of witnesses. You will also appreciate that this is a very difficult time of year because many people are on holiday. Most of these witnesses are medical witnesses and locums have to be arranged and the problems, I am afraid, compound themselves. Miss Emmerson is doing the absolute best she can to sort these witnesses out and I very much hope that we will not be subjecting anybody to any gaps, but I have to say that at the moment it is a little bit unpredictable when we are going to have which witness. We will do our best to keep everybody informed.

THE CHAIRMAN: Indeed. You are quite right, there has been some slippage of the time already. The other thing I am not quite sure of is that I do wish to give the Panel some time, on a regular basis, to keep up to date with their reading material, the transcripts and also their own notes that they are making, to make sure that in a case of such complexity that that they are on top of the evidence that they are hearing.

MS SMITH: Sir, you mentioned that before. It may be, if I may respectfully suggest it, that you would care to think about that with the Panel and we can have it built into the timetable in some way. You will appreciate that our difficulty is that we line up witnesses because we are very anxious not to have gaps and subject the Panel to gaps when they do not want them. Then of course we get involved in them having to stay overnight because we do not reach them that day. So if there are going to be times when you would actively like to have a little gap so that you can keep up, which I have to say I think is a very good idea, we would need to know when those gaps are.

THE CHAIRMAN: Indeed. I obviously did not anticipate any gaps coming this week, because it is the start of the case. But from next week onwards we will need to dedicate some time to reading. The Panel Members will still be here with their evidence, their notes and the transcripts. So we will do some work on this over the weekend, and on Monday I can have a meeting with the Panel Secretaries, both Caroline and Chris, and we can work something out on that basis, if that is acceptable to everybody.

Can I then thank you all. We will now rise and resume the hearing at between 11 and quarter past 11 tomorrow morning.

(The Panel adjourned until 11.00 am on Thursday, 19 July 2007)

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