Wakefield Essay--Essay Eight

Most critics of Dr. Andrew Wakefield know the contents of the five-page Lancet study, released late in Feb. 1998, better than theologians know the Gospel of John. But just as no competent biblical scholar would try to read the text of the Gospel of John without reference to the philosophical and historical background at the time of its writing, so no real interpreter of that Lancet article should read it without knowing something of the "thick description" of its origin and production, which I have tried to provide here. Now we are almost ready, finally, to look at that document, to see what it claims and does not claim, and to understand how it became the source of immense controversy in England for several years after its publication. But a few more preliminary points beckon.

As mentioned above, the study which would result in the Lancet article was derived from the first 12 cases of children with bowel symptoms and developmental regression referred to Prof. John Walker-Smith from general practitioners or pediatricians. Most of the children (10) were from England but one was from the Channel Islands and one from the USA. They cut it off at 12 cases because that was a reasonable size for a "case study" and preliminary results presented themselves. Indeed, Kanner's famous article 1943 article on autism, that sparked the entire field of autism research, was based on observations of 11 children. Several of these 12 children would eventually become litigants in the class action lawsuit being developed by Richard Barr, but their status with respect to the lawsuit during the time of examination, July 1996 -January 1997, was not known to the researchers and clinicians. Just to be clear, when pressed on this point, Dr. Wakefield said that they may have known that one of the children held a Legal Aid certificate at the time of colonoscopy, but at the time that each of the children was referred, none was involved in the lawsuit. A Feb. 20, 1997 memo from Walker-Smith to Wakefield was seemingly the first sign that researchers and clinicians were aware that some of the children's families were involved in Barr's lawsuit. This might affect the way that they would look at future cases, but the 12 individuals who became the subject for the Lancet piece had already been examined by that time.

In the run-up to the publication of the Lancet article late in Feb. 1998, Wakefield not only circulated the article to his colleagues in the Medical School but also indicated, in a letter to them, that if called upon to give an opinion on the safety of the MMR vaccine, he would recommend, by virtue of lack of convincing safety studies, cessation of the MMR vaccine in favor of the "monovalent" (i.e., the measles vaccine). This recommendation was based on his conclusions for the aforementioned study he did for Solicitor Barr. He mentioned that he knew this position would be controversial and would not be shared by all, or even many, of his colleagues. Nevertheless, the Dean of the School of Medicine, Arie Zuckerman, decided that he would "pull out all the stops" upon the release of the Lancet piece. After all, his mission as Dean was to elevate the school to its former prominence. Even though he may have disagreed with Wakefield's conclusions on the MMR (and he certainly did), he felt that the article to be published in Lancet would be the perfect occasion for bringing the kind of notoriety to the school which so many people wanted. Thus, in preparation for its release date, he authorized the following: a 20-minute video explanation of the article, where Wakefield was featured for about eight of those 20 minutes, and a news briefing, at the time of the Lancet's publication. Zuckerman would chair that briefing and bring four of the thirteen authors of the study along with him. He would field questions from the journalists from the podium and assign them to one of the four researchers or clinicians sitting at table on stage. All agree that all of these preparations constituted a highly unusual procedure in releasing a five-page article.

One point should be clarified here. Many of Wakefield's critics have rather thoughtlessly said that Wakefield not only was supportive of this arrangement but that somehow he "called" the press conference or "made" the video. For example, Dr. Paul Offit, in his highly critical assessment of Wakefield, begins his treatment of Dr. Wakefield with the following sentence:

A moment's reflection is all that is needed to see how unlikely that is, especially for those who are in academia. Individual professors have no public relations arm; the school does. Individual professors, especially those still "on the rise," don't have authority to order people around to make videos and set up news conferences. Deans do. That it is much more likely that the moving force behind all the publicity for the Lancet piece was the school, in the person of the Dean, than some secret power that Dr. Wakefield had to orchestrate all of this (including making the Dean play the role he did), ought to be obvious.

Well, February 1998 came. The paper was released. The first reaction you might have, however, in looking at the Lancet piece 11 years after its publication is one of "underwhelmment," if you permit the word. It isn't the gold standard of investigations--a controlled clinical trial. It simply reports on "what we have seen." And, when you get right down to it, the "report" consisted of certain medical findings--of certain nodular formations in the terminal ileum (that section of the short intestine that connects to the large intestine or colon)---and of reports of parents regarding when their child was administered the MMR. The interpretation of the data was similarly muted:

That is, what the study in its essence was saying was that three things seemed to be associated in time with each other in the 12 children: gastrointestinal distress, developmental regression (autism spectrum disorders, particularly) and the MMR (the "environmental trigger"). Not only is language of causation absent, but language even of correlation isn't present. Because Walker-Smith and Wakefield were currently investigating up to 300 children with similar complaints, it was far too early even to advance a causal hypothesis, much less to make causal findings. In other words, this was a "first look" into a baffling problem, a sort of "heads up" as to something mysterious that certainly would require more detailed examination, hypothesis formation, hypothesis testing and, perhaps eventually, a thesis that could be defended. Another sentence from the paper is important in this connection:

In fact, to be fair to the authors, they did make a claim in the piece that has become hotly debated in future research, and that is whether there is such a "syndrome" as autistic enterocolitis, which this paper claimed existed in the children. This syndrome, as described by Wakefield, consisted of two things: a large intestine (colon) inflammation and a swelling of the lymph glands predominantly in the terminal ileum of the small intestine. This syndrome, Dr. Wakefield argued, might be correlated with a child's autism. It isn't the purpose of this paper to assess the validity of that theory, though it remains the subject of robust debate.

But why, if the article is underwhelming in its claims, did it become, figuratively speaking, the face that launched a thousand ships? It became so because it was, from the beginning, encased in the interpretive framework of the press briefing and the video released to the media. And, when you get down to it, there was only one question at the news briefing that led to huge headlines in the British press. The question was raised whether this study implicated the safety of the MMR vaccine. As we know by now, that question was a potentially explosive one because of England's difficult history with the MMR in the first decade of its administration. The Dean turned to Wakefield for a response, fully knowing what he was going to say. And, Dr. Wakefield responded as we now should have expected--that he wouldn't recommend further use of the MMR until further studies were done on its safety, and that the monovalent vaccine (i.e., the measles vaccine) was a suitable alternative for the time being. The Dean then said that there certainly would be disagreement with that statement, but the moment was over...

Or so he thought. In the ensuing days the headlines screamed from some of England's most visible daily newspapers, to the effect that a prominent doctor was rejecting the "triple jab." As those who have been at the center of a news tsunami often relate, once this kind of headline comes out, the issue is removed almost completely from your hands. Indeed, over the next few years, the rate of administration of the MMR in England continued to decline, albeit at a more rapid pace, health officials scrambled to try to demonstrate the safety of the MMR, additional cases of measles were reported and, as recently as June 2008, measles were found to be once again "endemic" in England, fourteen years after measles was supposed to be wiped out. Those who have fought so hard to eliminate this potent virus are, no doubt, livid over the situation. The easiest thing to do is to lay the blame for all of this at the doorstep of an individual and to try to discredit him professionally and personally.

But let's reflect on this issue for a moment, before returning to a few more points about the Lancet article. I would like to use a "comparative hypothetical" here, a staple of legal education, to consider the issue more precisely. Let us suppose, for sake of argument, that a prominent judge or law professor in the United States does a "study" and then concludes that the US tax system is not only unfair but also is unconstitutional. Let's say s/he further argues that the income tax itself violates the US Constitution. This would be the fiscal equivalent of what Wakefield was arguing. Or, perhaps even more than Wakefield was arguing. Wakefield wasn't saying that the MMR was dangerous or that vaccines were bad; he was just raising questions about MMR safety and recommending a return to the "single jab," which had been used since 1968. But let us return to our judge or law professor. If s/he made such an argument, it would probably merit a mention tucked in page 12 of some newspapers. Someone of equally high stature would write an op-ed piece to the New York Times declaring that the good judge/professor was mistaken in reasoning for X or Y reasons. After a week, the issue would completely disappear, people would sort of shake their heads about the judge and go back to their lives, paying their taxes with reluctance but not really thinking that they should alter their lives. What is it, then, that enabled a person in early mid-career in England, who had just been promoted to "Reader," who had no previous experience in autism research, who was one of 13 authors of a piece, to make one statement to journalists about preferring the monovalent to the polyvalent vaccine, and then causing England's vaccine house of cards to come tumbling down?

The answer lies in the fragility of England's public health system in the 1990s. As mentioned before, it didn't have the most convincing track record on vaccine safety in the 1990s. People were already a bit skeptical of the health authorities. What Dr. Wakefield did was to voice some of the skepticism, though from a position of higher visibility. Should he have kept his mouth shut because the health authorities hadn't established their own credibility with the population at large? That, in fact, is a very interesting ethical question--of what you should say to which groups about which beliefs. An analogous situation might be whether a preacher should share his/her doubts about the validity or truth of faith with members of his/her congregation. For the sake of their "spiritual" health, should s/he keep thoughts to him/herself?

Well, while ethicists and all of us, really, could debate this question, another question, on whether he would recommend the continued use of the MMR, was on Dr. Wakefield's plate. The question was pointedly directed to him by the Dean of the Medical School. What would he recommend about the MMR's safety? He recommended the use of the monovalent. The monovalent was available in England at that time, contrary to what some of Wakefield's critics have said. It was withdrawn, however, with only the MMR available, later in that year--in August, 1998.

Should Wakefield have said what he said? Maybe so, maybe not. But certainly the Dean knew he was going to say it. And, if people think that statement caused the "measles" crisis of the next decade in England, shouldn't the burden equally or more be placed on the public health authorities for not being able to make a convincing case for its safety? After all, there are hundreds of them and one of him. Indeed, if he is to blame, what kind of society are we, really?

In fact, if anyone wants to parcel out "blame" for Dr. Wakefield's statement at the news briefing, some should fall on Professor Zuckerman for orchestrating the media circus relating to the publication of the article. Indeed, some blame might as well fall on the Lancet itself for publishing the article. After all, it was not as if the Lancet is a "vanity-press" publication. It has various levels of scrutiny and review, and only the articles that seem to suggest promising research directions are published. So clearly is the Lancet implicated in the "scandal," if indeed that is the right word, that the editor, Richard Horton (who was, in fact, a former colleague of Wakefield at the Royal Free Hospital), had to manufacture unconvincing reasons for the article's publication when pressed on the subject six years later (see below).

Therefore, to look at the events surrounding the publication of the Lancet piece, and the subsequent decline in MMR vaccination rate in England as the "fault" or blame of one person is not only naively simplistic but also defies common sense. If we play the "fault" game, there is the vanity of Zuckerman for publicity, the eagerness of Horton for a medical controversy, the failure of British health authorities to convince an unconvinced public, and the insatiable appetite of the English press for sensational blowing up of stories. Then, there is the statement of Dr. Wakefield. Rather than playing the "blame" game, however, one might choose to see the controversy sparked by his statement as a something useful in answering the basic question of the safety of the MMR--which was a legitimate one in the minds of many people.

There were two things appearing in the Lancet article that, in my judgment, were infelicitously stated and that have taken critics down rabbit holes that ultimately were misleading. First, the paper states,

This statement gives the impression that the practices pursued in the study were expressly approved by the Ethical Practices Committee in a decision of that committee. The only decision so made was in Dec. 1996. That decision was, as stated above, only for three additional items to the clinical protocol for the successor study to Study Two (blood draws, urine tests, CSF tests). And, this approval was only given prospectively--i.e., for subjects to be investigated after mid-December 1996. By this time the first 10 or 11 of the 12 subjects for the Lancet study were already scoped, imaged and punctured. How, then, could the study possibly be ethically approved, if approval came only after almost all of the children had been investigated? It is here that most critics of Dr. Wakefield have cried "Foul!" and this is the basis of several of the General Medical Council charges.

The answer to the question actually lies in the fact of Prof. John Walker-Smith's blanket ethical approval, described earlier. This ethical approval for research was granted him by the Royal Free School of Medicine before he began his work with them early in 1996. This approval covered the children in the Lancet study; it "covered" not simply the clinical work, which needed no approval at all as long as the tests were "clinically indicated," which Prof. Walker-Smith said they were, but the biopsy work done by Dr. Wakefield.

But the two lines just quoted could be confusing to people, especially since the quotation above gives the impression of a specific decision of the Ethical Practices Committee to approval the investigations. Actually, the approval of the investigations rested on the blanket ethical approval possessed by Dr. Walker-Smith. That approval was originally granted him by the Ethical Practices Committee earlier in 1996 when he transferred to the Royal Free Hospital from St. Bartholomew's. Problem solved, even if one would have wished for a clearer statement in the Lancet paper.

Second, critics have pounced on the statement regarding funding of the study. The Lancet article says:

Ah, isn't this precisely the place where the 55,000 Pounds was banked after the flurry of correspondences in May - July 1997? Doesn't this, then, suggest that Wakefield knew the money had come from Barr to the Royal Free NHS Trust and then to the study? Isn't there, then, a patent conflict of interest here?

The answer is a clear "no." On the one hand, as we have seen, the 55,000 Pounds was for Study One, which didn't get underway until Oct. 1997, well after Study Two (the Lancet study) was completed. But, even more to the point, the money provided for the Lancet study had previously been granted to the researchers by the variety of sources quoted in the 1998 article. In other words, the money for the Lancet study came through an independent grant of money from the Special Trustees themselves. Researchers are well aware of how various pots of money might come from the same source; in this case it would have been helpful (in hindsight) had the article spelled out the distinction from Study One. Yet, from the perspective of 1997-98, there was absolutely no reason to think that any conflict existed and so an explanation distinguishing sources of money would have been odd, to say the least.

See my summary of Kanner's work and its significance: http://www.drbilllong.com/Autism/Kanner.html

See the following news article from later in 1997: http://briandeer.com/mmr/st-jaws-warning.htm

A recent article summarizing the state of the question by Dr. Wakefield is: "Autistic enterocolitis: Is it a histopathological entity?-reply," Histopathology 50 (2007), 380-84.

The reference, for those unfamiliar with classical mythology, is to the beauty of Helen of Troy, which led to her abduction by Paris and the subsequent Trojan War, memorialized in Homer's Iliad . The phrase is actually derived from Christopher Marlowe, a contemporary of Shakespeare.

http://www.independent.co.uk/life-style/health-and-wellbeing/health-news/official-warning-measles-endemic-in-britain-851584.html

Here is a discussion of the question: "The UK had a single dose measles vaccine program since 1967. The single rubella and mumps vaccines became available in the early seventies. The MMR vaccine was introduced in 1988. When parents started requesting the monovalent vaccines in increasing numbers, the DOH decided in August 1998 to withdraw their license. Those who could afford it crossed the Channel to get their children vaccinated or purchased the single vaccines at private clinics." http://www.whale.to/a/ya45.html.

The following article gives some vaccination figures for England in the years before and then following the release of the Lancet article. http://www.guardian.co.uk/society/2007/jul/08/health.medicineandhealth1 According to the article, at the time of the press conference 91.5 per cent of children in England had the MMR jab by the time the turned two. After the headlines of the next weekend, MMR immunization rates dropped to 87.4 percent. The lowest ebb was 79.9 percent nationally, with lower figures for some sections of London.

Wakefield Paper: Essay Eight