Managing Editor's Note: The Wakefield family crest bears the latin "Arudua vinco" which translates to "I conquer difficulties." We can't thank Dr. Wakefield enough for his dedication to our children.
By John Stone
‘If we knew then what we know now we certainly would not have published the part of the paper which related to MMR, although I do believe there was and remains validity to the connection between bowel disease and autism.’
From the moment Richard Horton, editor of the Lancet, spoke these words on the BBC evening news of Friday 20 February 2004 Andrew Wakefield’s career lay in tatters. For six years Horton and the Lancet had been under pressure over his decision to publish in February 1998 an ‘early report’ Ileal-lymphoid-nodular-hyperplasia, non-specific colitis and autism in children of which Wakefield - a senior researcher at the Royal Free Hospital in London - was lead author. At publication time Wakefield was already an author of more than a hundred peer review publications, but none before or since attracted the attention of this one. The paper, a series study of 12 consecutively referred cases, related to a sub-group children who had suffered adverse reactions to MMR vaccine, and hypothesised but did not confirm a connection between their symptoms and the vaccination.
Nevertheless, by implication the study struck at the heart of public health policy: the Royal Free Medical School called a press conference, and there was instant controversy. The British government and medical establishment never forgave Wakefield. They weren’t that happy with Horton either, and he knew it.
Horton’s decision to go to the BBC in February 2004 had been precipitated by an extraordinary meeting at the Lancet offices two days previously. Wakefield’s 1998 paper had been investigated by a freelance journalist Brian Deer on behalf of the Sunday Times. According to Horton – giving evidence the UK General Medical Council in August 2007 – Deer had been dispatched with Liberal-Democrat member of parliament, Dr Evan Harris, in a last ditch attempt to rescue a failing story, held over from the previous week, and considered to weak to publish. Also present there with Wakefield, were Profs John Walker-Smith and Simon Murch, the two doctors presently on trial with him at the GMC, and another Royal Free doctor, the neurologist Peter Harvey.
Deer presented a raft of allegations about the conduct of the study, and unethical procedures conducted against the children in the study. These were rebutted by the doctors, and were neither upheld by the Royal Free or in turn the Lancet. The sticking point, however, came over the fact that Wakefield, alone of the Royal Free doctors, had been hired by the Legal Aid Board to investigate the possibility of class litigation against the MMR manufacturers. Confronted by Deer, Horton denied that he had known of this, and Deer at last had a story. Horton’s decision to go public that Friday evening anticipated the publication of Deer’s article in the Sunday Times (and comically led to him being sued by Deer in the small claims court). But Horton’s declaration on its own ignited a media explosion and by the following morning he had also told the BBC that there was “a fatal conflict of interest” and the research was “fatally flawed”. By Saturday, tea time, the Secretary of State for Health, John Reid, had requested that the General Medical Council investigate the case “as a matter of urgency”. And all before Deer’s story had gone to press for Sunday morning.
This episode smacks of gross media manipulation. Conflicts in medicine and science are commonplace – something that hitherto would not have raised an eye-brow was being foisted on the public at large as if it was grave misconduct – and that was even before considering the truth and validity of the allegation, which at the time would have been extremely hard to establish either way, and was certainly denied by Wakefield. Four years later when Wakefield finally produced powerful documentary evidence of his innocence at the General Medical Council no one in the media reported, although several journalists – including from the BBC and The Times - were present.
The outlandishness of what had happened was reflected in a remarkable passage the book which Horton was to publish within months of the episode, MMR Science and Fiction: Exploring the Vaccine Crisis, in which he recalled his dinner engagement on the Monday following these events, and result of the Health Secretary’s immediate request that the GMC investigate:
In truth, they (the GMC) had not a clue where to begin. At a dinner I attended on 23 February (2004), one medical regulator and I discussed the Wakefield case. He seemed unsure of how the Council could play a useful part in resolving the confusion. As we talked over coffee while the other dinner guests were departing, he scribbled down some possible lines of investigation, and passed me his card, suggesting that I contact him directly if anything sprang to mind. He seemed keen to pursue Wakefield, especially given ministerial interest. Here was professionally led regulation of doctors in action - notes exchanged over liqueurs in a beautifully panelled room of one of medicine's most venerable institutions (p7-8)
This could almost be a comic parody of the British establishment at work if it was not for real. But Horton’s decision to turn on Andrew Wakefield has been one of the long neglected (and tragic) turning points in the Wakefield affair.
I have long been curious about Horton’s role in this saga. When I wrote recently to the president of the GMC, Sir Graeme Catto, to ask him to explain Horton’s involvement (and potential misconduct), he declined to respond, but passed my open letter to their investigatory branch. I received this reply:
In short, I can assure you that the instigation of our investigations has absolutely nothing to do with any conversations which ‘medical regulators’ may have had with Dr Horton at the dinner described in his book. If such conversations took place, they were not reported back in to our investigations team who were looking at the case at the time. This being the case, the content of any such discussions had absolutely no impact at all on any of the decisions made about whether to proceed to investigate the case or, indeed, how such investigations should be carried forward.
How could they possibly know whether their investigations have been influenced by the conversations if they have not even asked about it, and are totally incurious even now that it has been pointed out? It does not matter by now what departures we have from ordinary process, or whether there is even prima facie evidence of misconduct. The trial must go on.
Although the “medical regulator” Horton met that Monday evening in February 2004 did not seem concerned about the ethics of exploring ways in which Andrew Wakefield might be prosecuted (and with the star witness!), he certainly did not seem convinced that Wakefield had done anything wrong. This may have been because undisclosed conflicts of interest are so common that you could not practicably start prosecuting them (where would it end?) but also (as he may already have considered) that acting as an expert witness for the courts did not by convention constitute a conflict at all. In fact, this argument was helpfully put by a legal counsel (in the British system ‘a barrister’) Robert Hantusch in a letter to The Times the following day (24 February 2004):
... the courts do not consider that the engagement of someone to act as an expert witness in litigation has the effect that that person is then biased. Indeed, if this were the legal position, no paid professional could ever at any time give evidence to a court.
And this defence was also taken up by a witness on the other side of the case, Elizabeth Miller, when it was pointed out in the satirical journal Private Eye that she had a like conflict (if it was such):
...there can be no conflict of interest when acting as an expert for the courts, because the duty to the courts overrides any other obligation, including to the person from whom the expert receives the instruction or by whom they are paid. (19 March 2004)
As of the present, of course, Miller has yet to be summoned before the GMC.
But was Horton’s allegation that Wakefield had withheld information about his work with the Legal Aid Board really true? At the end of the week (27 February 2004) the Independent newspaper finally located striking evidence in Wakefield’s defence: a letter published on 2 May 1998 in the Lancet, nine weeks after the controversial study, in which Wakefield replied to a correspondent, Andrew Rouse, who raised the possibility of “litigation bias”:
A Rouse suggests that litigation bias might exist by virtue of information he has downloaded from the internet: from the Society for the Autistically Handicapped. Only one author (AJW) has agreed to help evaluate a small number of these children on behalf of the Legal Aid Board [emphasis added]. These children have all been seen expressly on the basis that they were referred through normal channels (eg, from general practitioner, child psychiatrist, or community paediatrician) on the merits of their symptoms. AJW has never heard of the Society for the Autistically Handicapped and no fact sheet has been provided by them to distribute to interested parties. The only fact sheet we have produced is for general practitioners, which describes the background and protocol for the investigation of children with autism and gastrointestinal symptoms. Finally, all those children referred to us (including the 53 who have been investigated already and those on the waiting list that extends into 1999) have come through the formal channels described above. No conflict of interest exists.
The information that Wakefield (and Rouse) were referring to was a fact sheet compiled by the legal firm Dawbarns who were pursuing a class action against the MMR manufacturers at the time, downloaded from an independent website. So, while Wakefield denied that the matter constituted a conflict he had clearly stated his involvement in the litigation at that early stage. Unfortunately, the Independent story made little difference. The BBC, with its commitment to balance and impartiality long forgotten, refused to report this (though I for one personally bombarded the head of news Richard Sambrook with emails), and only the Telegraph doctor James Le Fanu took up the issue (2 March 2004). It is worth quoting the entire passage from his column, headed ‘The truth about MMR must be revealed’:
The Government finds itself in an invidious situation over the MMR/autism controversy, having painted itself into a corner by denying parents the option of the single measles vaccine. They, thus, have no alternative other than to insist the MMR is totally safe - irrespective of evidence that might emerge to suggest the contrary.
Their difficulty is that this position is now looking a lot shakier than it did even a year ago. Several further independent studies have confirmed the association of the syndrome of regressive autism with chronic bowel disorder that was originally described by Andrew Wakefield. More recently, research has confirmed the presence of the measles virus in the gut and spinal fluid of affected children.
This may not constitute "proof" and, indeed, a former colleague of Dr Wakefield challenged the significance of these findings in the Lancet a fortnight ago - and he may be right to do so. None the less, it is beginning to look as if, as neurologist Peter Harvey points out in the same issue, there is now "a step-by-step cascade of evidence" linking the MMR vaccine to some cases of autism.
This could explain the assault on Dr Wakefield’s integrity. The validity of his original findings, it is claimed, may have been compromised by a conflict of interest involving research funds that he failed to disclose. This might be relevant if it were true, but it is not, as anyone can check for themselves: Dr Wakefield acknowledged the source of his funding in the Lancet in 1998. It would seem to be that neither the Government nor the medical establishment can afford for Dr Wakefield to be vindicated - and they are getting pretty desperate.
But, remarkably, the role of the man at the centre of the non-disclosure allegation has largely escaped public scrutiny. In MMR Science and Fiction, Horton, while elaborating on the circumstances which led him to throw Wakefield to the wolves skirted delicately around the evidence that Wakefield did indeed disclose his work with the Legal Aid Board.
Critically Horton reproduces an apparently heated exchange from a parliamentary committee meeting of 1 March 2004 between Evan Harris, and the Lancet’s boss, Crispin Davis, Chief Executive of Reed Elsevier (p.50-1). Both men wave the letter of 2 May 1998 around, Davis citing the statement that there was no conflict of interest, but neither places on the parliamentary record that Wakefield had stated in that very letter that he was engaged in the litigation, and whether it was a conflict or not, it had certainly been in the public domain from that time. (But while we are on the subject of conflicts of interest, perhaps Davis needed to point out -and Horton certainly failed to do so – before becoming sanctimonious about Wakefield that he was appointed a non-executive director of MMR defendants GlaxoSmithKline in July 2003.)
When he gave evidence to the GMC in August 2007 Horton stated that he had not understood from the declaration that Wakefield’s involvement pre-dated the publication of the study two months earlier. The only trouble with this was that Rouse’s letter, forwarded by the Lancet to Wakefield on 2 April 1998, was according to Wakefield’s testimony actually dated 4 March, four days after the publication of the study – which would suggest that any such misunderstanding on Horton’s part was either disingenuous in the extreme, or simply incompetence.
The problem with Horton’s evasions was compounded by his transparently flawed account in his book of the session in the Lancet offices with Brian Deer on 18 February 2004:
There the consensus ended. Wakefield admitted that he had been commissioned by the Legal Aid Board to conduct a pilot study on behalf of parents of allegedly MMR-vaccine-damaged children. Some of his colleagues claimed that he had not disclosed this fact to them. Simon Murch and John Walker-Smith were visibly shocked by this revelation.
How anybody could have been shocked about a matter which had been in the public domain for six years is a mystery: in fact when presenting his evidence to the GMC in March 2008 Wakefield read a letter he had written in early 1997 to Walker-Smith and Murch explaining his decision to act as an expert in the MMR litigation – a line from it was subsequently quoted in a BMJ report (5 April):
If these diseases are found to be linked to the MMR vaccine, these children are the few unfortunate who have been sacrificed to protect the majority.
Thus, while there may not have been agreement between them on this, the claim that the matter was hidden from close colleagues would appear to be fanciful.
So what really happened at that meeting between the three doctors and Horton? At the GMC in August 2007 Horton described the pivotal moment of revelation as relating to the Dawbarns fact sheet which Deer had produced, which promoted the case against the MMR manufacturers and alluded to Wakefield’s involvement. It was Deer’s production of the fact sheet which purportedly caused discomfort to Walker-Smith and Murch, and left Horton denying to Deer and Harris that he had known of Wakefield’s enrolment by the Legal Aid Board.
Beyond the Wakefield-Rouse correspondence in May 1998, did Horton have any other occasion to learn of Wakefield’s Legal Aid work? Indeed, unlike Wakefield, Horton’s office itself was involved in a lengthy correspondence with Dawbarns, long before the publication of the Wakefield’s study in February 1998. In his testimony to the GMC in April 2008 rebutting Horton’s claim, Wakefield revealed stunning new information from a previously undisclosed 1997 correspondence between the Lancet and Dawbarns about the Dawbarns fact sheet to which Horton had been party. According to this exchange, at some point in March 1997, or just before, an employee of the UK Medicines Control Agency (later MHRA), Dr B D Edwards, writing in his private capacity, alerted Horton to the use of Lancet material (not the unpublished autism study) in the Dawbarns fact sheet – this included extracts from other articles by Wakefield and some tables. The Lancet then wrote to Dawbarns warning them they should apply to the journal if they wanted to continue to reproduce it. There then followed an extended letter from the lead lawyer for the case, Richard Barr, to Horton dated April 3, 1997, mentioning that Wakefield had given permission to refer to an article and citing a statement on the fact sheet:
There is convincing evidence of a link between vaccination and inflammatory bowel disease (including Crohn’s disease). It is a serious lifelong illness that has affected a large number of the children we are helping. We are working with Dr Andrew Wakefield of the Royal Free Hospital London. He is investigating this condition [emphasis added].
It was important for Barr to draw attention to Wakefield’s involvement, because it added moral weight to his case that the Lancet should allow publication. Horton wrote back denying permission and a lengthy correspondence ensued involving the Lancet ombudsman Prof Thomas Sherwood, in which a compromise was reached – this was concluded in the month of July 1997 just as the controversial study was being passed for publication, and presumably there would have been communications within the Lancet between Sherwood and Horton on the matter.
While it may have been a shock for John Walker-Smith and Simon Murch when Brian Deer produced the fact sheet in the Lancet offices because they had never seen it before, Horton claims that, in his role as guarantor of the ethics and reputation of The Lancet, it came as an even bigger shock to him because Wakefield had violated ethical guidelines by withholding disclosure of the Legal Aid connection. But when Wakefield finally produced this evidence to the GMC in April 2008 that Horton and The Lancet’s ombudsman had been engaged in extended discussions with the Legal Aid attorneys over their desire to cite work from their expert witness Wakefield in a fact sheet, it was barely reported: not, for instance, by the BBC or by The Times (although they had their journalists present), nor even by Brian Deer. Only in British Medical Journal was there a half-buried account by Owen Dyer (April 19):
Dr Wakefield’s defence challenged testimony given earlier by Richard Horton, editor of the Lancet, who said that he had not known before the article’s publication of Dr Wakefield’s work on behalf of MMR litigants.
Dr Wakefield alleged that newly uncovered documents reveal an extensive correspondence between the Lancet and Dawbarns, the firm of solicitors representing MMR claimants. These letters, several months before publication of the 1998 article, described Dr Wakefield’s work on behalf of the MMR litigants, he said. While he was "not impugning Dr Horton’s honesty," said Dr Wakefield, the documents proved "in my opinion beyond a shadow of a doubt that he was aware of all these factors."
Dr Horton, reached by email while travelling abroad, denied any foreknowledge of the conflict of interest, saying that the correspondence did not make clear Dr Wakefield’s role in litigation.
In most accounts of Wakefield’s Legal Aid connection, the media have generally accepted Horton’s description of his editorial judgement: if he had known of the connection before publication of the 1998 study he would not have approved it. But there is another possibility: that Horton only decided it was a significant matter long after the event. Indeed, two letters written by Wakefield to the Lancet on the MMR issue in (September 11, 1999 and August 26, 2000) after the disclosure of May 1998 that he was working for the Legal Aid Board were passed for publication without any such declaration.
Horton’s inconsistency was further exposed when in 2004 – after the Wakefield affair blew up - the Lancet held out for 5 months over publishing a letter from Mark Geier regarding Michael Pichichero’s non-disclosure of pharmaceutical company funding in another vaccine autism study ‘Mercury concentrations and metabolism in infants receiving thiomersal: a descriptive study’ (2002). Pichichero’s silence over his competing interests in this paper stood in contrast to information revealed in an earlier study, which had the following declaration:
The author has received research grants and/or honoraria from the following pharmaceutical companies: Abbott Laboratories, Inc.; Bristol Myers Squibb Company; Eli Lilly and Company; Merck&Co.; Pasteur Merieux Connaught; Pfizer Labs; Roche Laboratories; Roussel-Uclaf; Schering Corporation; Smith Kline Beecham Pharmaceuticals; Upjohn Company; Wyeth-Lederle.
This lapse was only resolved after I had posted on it twice in British Medical Journal Rapid Responses. To all appearances this non-disclosure – which hid extensive commercial interests - was far more compromising: but to the Lancet it was barely worth mentioning, and not to be compared to the perfidy of Wakefield – indeed, they only agreed to publish a version of the Geier letter if Wakefield was not mentioned in it. Some conflicts in Horton’s world are evidently more fatal than others.
Many months after Wakefield’s evidence a new statement was finally obtained by the prosecution at GMC from Horton, presumably explaining as best he can the apparent discrepancies in his earlier evidence, but the hearing was having trouble pinning down a time for him to be questioned about it. Though Horton’s office is less than a mile up the road from the GMC hearing, he will apparently be engaged in an important peace mission to the Middle East when it next sits in January.
It was always the strategy of the British scientific establishment and government to isolate and destroy Andrew Wakefield – to make him look as if he was standing scientifically and intellectually on his own, and to make sure when they crushed him they discredited all further opposition or dissent on the vaccination issue. In the US context Horton’s book MMR Science and Fiction would be an almost incomprehensible oddity. There is, for instance, only a single mention of thimerosal, which apparently is just another eccentric concern of Wakefield’s. In essence the alleged “vaccine crisis” of the title is entirely about Wakefield and the supposed gullibility of people who doubt official science. Horton’s book is not ultimately about scientific truth, it is about who is credible – we are being told not only is Wakefield not credible, most importantly the parents of vaccine damaged children are not credible either. And cleverly nuanced as Horton’s argument is for a liberal readership, his decision to turn on Wakefield has behind it a highly illiberal and authoritarian basis, in which the interests and voices of the patients and their families are to be finally stamped out. It is ultimately just stage management, and a stab in the back for open debate.
John Stone has an autistic son, and lives in London.