British science accused in the wake of the MMR scare

I was originally going to blog this yesterday, but Dr. Oz’s offenses against science and medicine on his show that aired on Tuesday kind of pushed it out of the way. It’s not that I didn’t think the third part of Brian Deer’s expose of Andrew Wakefield’s fraud worthy of my attention. Rather, the Oz thing really got me peeved, peeved enough to push aside (temporarily, at least) Brian Deer’s deconstruction of how the editors of The Lancet scrambled to cover their proverbial asses, which they proceeded to do with alacrity, as the title of Deer’s article implies: The Lancet‘s two days to bury bad news.

I’ve been critical of The Lancet before for publishing Andrew Wakefield’s case series. Indeed, to this day, I hadn’t been able to figure out how Richard Horton, the editor of The Lancet, kept his job in the wake of l’affaire Wakefield, particularly after Wakefield’s massive conflicts of interest had been revealed in 2004, as well as the possibility that Wakefield had subjected vulnerable children to invasive procedures that were not medically indicated. The reason is not so much that I would expect peer review to have uncovered what we now know to have been blatant fraud. Peer review has a hard time doing that because the default assumption in science tends to be one of honesty, namely that what authors report in manuscripts submitted to journals does not represent falsified data. Oh, sure, editors and reviewers are fully aware that scientists will try to present their data in such a manner to put the best possible spin on their experiments, to make their story as persuasive as possible. That’s expected. What is not expected is outright dishonesty, falsification of data, the offense by Wakefield for which Deer presented strong evidence in his previous two articles.

No, what should have gotten Horton fired, from my perspective, is that he accepted such a poor manuscript. Even taken at face value and even if there had been no scientific fraud, Wakefield’s manuscript, a case series of only 12 children that, even viewed in as favorable a light as possible, didn’t support the hypothesis that MMR vaccination was somehow associated with a new syndrome consisting of regressive autism and enterocolitis. It was the thinnest of thin gruel, which, again, even if viewed in the best possible light, didn’t belong in the pages of The Lancet. Maybe in the pages of some bottom-feeding medical journal or another, but not in The Lancet. This is particularly true given the explosive nature of the implications of Wakefield’s paper, which should have resulted in more caution on the editors’ part to make sure that all the i’s were dotted and t’s crossed.

Of course, in most cases, the consequences of publishing such an article would be a temporary blot on the reputation of a journal, soon forgotten. Not in this case. In this case, the publication of Wakefield’s publication in The Lancet, coupled with Wakefield’s media whoring and the eager acquiescence of the British media, ignited a scare about the MMR vaccine that led parents to abandon the MMR in droves, driving the MMR uptake rate to levels below that necessary to maintain herd immunity. As a result, measles came roaring back in the U.K. such that it is now endemic again. Can Horton be directly blamed for this scare? Not exactly. But his irresponsibility did play a significant role in igniting the scare and at the same time permanently tarnishing the reputation of the journal for which he was responsible. In other words, he screwed up. He had no way of definitely knowing that his screwup would have such far-reaching consequences, although he should have had an inkling, but them’s the breaks. His screwup, instead of being quickly forgotten, leaving him to continue his career with minimal consequence, resulted in consequences that could not be ignored.

If I were in charge of The Lancet, I would have canned Horton’s ass in 2004 after Deer’s first set of revelations, or, if that were not possible (it’s not easy to fire a journal editor), I would have declined to renew his contract when it expired, assuming he has a contract.

Before I go on, though, I must point out one thing. After reading his installment, it is even more clear to me than it was a week ago when I blogged about it that Deer’s attack on Drs. Offit, Goldacre, and Fitzpatrick for supposedly being part of the “old boys network” of physicians downplaying Wakefield’s offenses and his investigative journalism was wildly off key in relationship to this most recent article, which criticizes British medical authorities and the Lancet for letting the Royal Free Hospital and the UCL investigate themselves and laments how medical authorities often don’t take fraud seriously enough. Neither of these are positions that Drs. Offit, Goldacre, or Fitzpatrick would be likely to disagree with in the least, and none of them that I’m aware of, other than Fitzpatrick, ever even criticized the bringing of charges against Wakefield before the GMC.

Deer is completely on key, however, when he describes what happened when the Wakefield situation blew up in 2004 after Brian Deer’s first set of revelations was published. In retrospect, it is not surprising (actually, it shouldn’t have been surprising at the time) that Horton had every motivation to try to minimize the damage to his journal and its reputation, and apparently that’s just what he did, as Deer points out as he describes what happened after his meeting with Horton and the editors of The Lancet in 2004, in which he laid out the evidence for Wakefield’s misconduct:

I had assumed that when I finished Horton would say that an investigation was needed to untangle these complex matters. There were at least three strands: possible research fraud, unethical treatment of vulnerable children, and Wakefield’s conflict of interest through the lawyer. But within 48 hours, and working with the paper’s three senior authors, the journal was to publish a 5000 word avalanche of denials, in statements, unretracted to this day.5 6 7 8 9

It can’t be emphasized enough that Wakefield took advantage of a vulnerable population (autistic children) in order to enrich himself. I mention it here again because it is a very important point.

During the GMC hearings, Horton claimed this:

“In this particular case,” he [Horton] told the GMC tribunal of three doctors and two lay members, seated to his right at the hearing, “we went to the vice-dean of the Royal Free, laid out the nature of the problem, and asked him to investigate and come back to us, as best he could, with his own judgment of the veracity or not of the allegations. In addition to that, we would look at the documentation as best we could and try and form our view as to whether those allegations were true.”

But what really happened was this:

But documents, emails, and replies obtained under the Freedom of Information Act reveal no formal investigation. What emerges is merely a scramble to discredit my claims during the 48 hours after I disclosed the information. They show the journal’s editor, the paper’s senior authors, and the Royal Free medical school, frantically mobilising against me. Were it not for the GMC case, which cost a rumoured £6m (€7m; $9m), the fraud by which Wakefield concocted fear of MMR would forever have been denied and covered up.

Deer then proceeds to describe exactly how this was done. Basically, there was no independent investigation. Right after Deer left Horton, Horton met with the three principal authors of The Lancet paper and devised a strategy wherein all impropriety was denied except for Wakefield’s conflict of interest in having accepted money from lawyers to develop evidence to support lawsuits against vaccine manufacturers, which they did their best to minimize as an offense as a failure on Wakefield’s part to disclose. Fortunately, that part appears to have backfired, as Horton’s concession that Wakefield had had a conflict of interest ignited a media firestorm:

His actions sparked a media firestorm. Although denying all of the most serious of my findings (now proved), he conceded that Wakefield had a conflict of interest–and that weekend was what journalists call “slow.”

The BBC was on the story within half an hour of the statements’ release. Independent Television News called Harris. And all of Fleet Street knew the thrust of an impending splash in the Sunday Times, the UK’s market leading Sunday broadsheet.

The furore blazed from Friday until Wednesday, and beyond.

Science is an enterprise that, because it is a human enterprise, can be corrupted when its practitioners do not possess the personal integrity to be honest in reporting their results. Andrew Wakefield is clearly just such a dishonest man, whose ambition and greed led him not only to accept money from lawyers to develop scientific “evidence” they could use in court while suing vaccine manufacturers, but then to falsify evidence for his case series, misrepresenting the clinical histories of several of the children, and then making plans to produce products based on his unsupported hypothesis that the MMR vaccine can cause autism associated with GI complaints, products that, according to Wakefield’s hopes, could make him many millions of dollars. Unfortunately, a combination of factors can provide motivation for such misconduct, including self-aggrandizement, becoming too enamored of one’s own ideas and insufficiently willing to give them up when they are not supported by the evidence, and just plain greed. While it’s obvious that Wakefield suffered from just plain greed, his ego almost certainly played a role.

It is also truly disheartening that, instead of taking the charges of fraud seriously, and trying to get at the heart of the matter, Richard Horton instead appears to have done his best at damage control. In this, he unfortunately follows a pattern that is all too common in science. An accompanying editorial by Douglas J. Opel, Douglas S. Diekema, and Edgar K. Marcuse, entitled Assuring research integrity in the wake of Wakefield addresses the question of how this can happen, be Wakefield and his misdeeds or other scientific fraud. They correctly point out that the problems that allow people like Wakefield to get away with what Wakefield got away with tends to be a systemic problem and that instances of fraud like Wakefield’s should be treated as adverse events. While this is a useful model as far as it goes, more useful is the concept that the culture of science needs to change:

We must transcend traditional hierarchies and authority gradients to empower everyone in the research enterprise–especially those on the front lines, such as research assistants, data analysts, and project managers–to raise questions and “stop the line.”12 We must train our research leaders–such as department chairs and medical school deans–to manage such inquiries. We must not allow it to be “customary” for journal editors “to discuss and take the word of those against whom the allegations are made.”3 Lastly, when allegations of research misconduct or unethical research are brought to the attention of research leadership, these leaders must recognise that they often have a conflict of interest in managing these allegations.

Most depressingly, it is very telling that it took Brian Deer’s investigation to bring the full extent of Wakefield’s fraud and scientific misconduct. In this case, scientists couldn’t keep an eye on their own house; it took an outsider to uncover the fraud. Science needs to do better. The consequences of not doing better are stark. Even though scientific research quickly refuted Andrew Wakefield’s claims with additional studies, science alone wasn’t enough to bury his fraudulent conclusions once and for all. I’m not even sure that Brian Deer’s revelations will be enough.