Lancet editor reverses himself: MMR and adverse events

Teresa Binstock
Researcher in Developmental & Behavioral Neuroanatomy
February 15, 2010

Circa 2010, the MMR autism controversy has not abated despite The Lancet's retraction of a peer-reviewed case-studies paper the journal's editor Richard Horton has described as scientifically sound (1-2). Indeed, the primary reason for the retraction appears to have been the researchers' having considered the possibility that the MMR vaccination may have initiated some children's regression into autism with gastrointestinal pathology (3).

There are two primary issues: Are measles mumps rubella (MMR) vaccinations etiologically significant in some cases of regressive autism? Are MMR vaccinations etiologically significant in the gastrointestinal pathology of some autistic children?

Mainstream media would have us believe the answer to each question is no: The MMR is neither a causal factor nor a co-factor in some cases of autism and has no relevance to intestinal pathologies in subgroups of children with autism or one of the other autism-spectrum disorders. However, findings in other peer-reviewed studies are consistent with the idea that MMR vaccinations induce adverse sequelae in some children.

Part 1: Richard Horton, The Lancet editor, affirms sound science in Wakefield et al 1998

In 2006, The Observer, a major London news magazine, printed an article by Sally Beck, wherein The Lancet editor Richard Horton said the scientific findings in Wakefield et al 1998 were valid.

'Horton was quick to confirm that the science in the paper, which looked at whether 12 autistic children also suffered bowel disease, was good.

'He reiterated his statement in his evidence to the GMC, "There was no question in my mind that subject to external peer review and editor debate, we should publish this work," he said. "The description of what seemed to be a new syndrome and its relations to possible environmental triggers was original and would certainly have interested our readers." ' (2)

Furthermore, the 1998, Wakefield et al finding of gastrointestinal pathology in a subgroup of autistic children has been confirmed numerously (4-11; see also 12-13); and in 2010, the American Academy of Pediatrics journal "Pediatrics" published two major reviews focusing upon evaluation and treatment of gastrointestinal pathologies in autistic children (14-15; see also 16-17).

Part 2: Richard Horton, The Lancet editor, reverses himself

In 2010, an article in the New York Times (18) made clear that Richard Horton is reversing his 2006 statements. He denounces the Wakefield et al 1998 study and -- perhaps most importantly -- admits that the 1998 article's vaccine/autism speculation became The Lancet's error which led to retraction. Consider statements from NYTimes blogger Tara Parker Pope:

'The study was retracted after concerns about ethical breaches by one of the study authors. In addition, 10 of the 13 co-authors have disavowed the study’s conclusions. ”We fully retract this paper from the published record,” The Lancet editors said in a statement.

'But the damage has been done. The paper has fueled fears about the risks of childhood vaccinations and autism, particularly the M.M.R. vaccine, despite numerous studies showing no link.

'This week, National Public Radio’s “On the Media” explored the role the media played in inflaming fears about vaccines and autism, asking how “bad science” made its way into The Lancet and the “collective psyche.”...' (18)

Irony abounds. A study whose findings have been numerously replicated has been retracted. Thus the 1998 article's primary conclusion - the description of a finding of gastrointestinal pathology in a subgroup of autistic children - is not going away. Perhaps the recantation by 10 of the 13 co-authors and the retraction by The Lancet was less about the intestinal pathology findings and more about the researchers having dared consider the possibility that, for some children, their regression into autism and their gastrointestinal pathology may have been initiated by the MMR vaccination.

Not suprisingly, Timothy Buie, M.D., and colleagues have been able to understand and express the core concern:

"In 1998, Wakefield et al... reported an association between ileocolitis and developmental regression in 12 children and coined the term “autistic enterocolitis.” From the same uncontrolled study they reported NLH [nodular lymphoid hyperplasia] of the ileum and colon as an abnormal finding in most children with ASDs... Wakefield et al also proposed [and stated as not proven] a causal relation between measles, mumps, and rubella (MMR) vaccination and autism, a suggestion that was later retracted by many of the original authors." (14)

Now, why would the editor of a prominent journal like The Lancet reverse himself so completely?  The answer may have been presented in the aforementioned NYTimes article, where Horton mentions new vaccines about to enter the market.

"I certainly hope that our retraction today will help to reassure parents that there really isn’t anything to be concerned about with the vaccine. I think there’s a history over many hundreds of years of anti-vaccine movements. We are going to see many, many more vaccines available to the general public, and we all have to be very vigilant about making sure that we build trust and confidence in these vaccines which are going to transform the landscape of health over the next generation." (18)

If data indicate an association between vaccinations and various autism-spectrum disorders, then new vaccines might be less well received. Should that happen, gross revenues and net profits for pharmaceutical companies that manufacture vaccines would be negatively impacted. Thus let us ask, is there evidence that MMR vaccinations may injure some children? According to peer-reviewed studies, the answer is Yes.

Part 3: The MMR and adverse events

NVICP: National Vaccine Injury Compensation Program (19)
VAERS: Vaccine Adverse Event Reporting System (20)
 
NVICP and VAERS exist because adverse effects associated with vaccinations have long been known. Although NVICP and VAERS recommend that even soft signals (reports of adverse reactions) merit concern, the emphasis for seeking soft signals is via professionals with credentials (20). In this schema, parental reports tend to remain virtually unheard. A major part of the heresy of Wakefield and his colleagues in 1998 is (a) they listened to parents who reported MMR-related regression into autism and MMR-related onset of bowel pathology, and (b) the researchers dared commit these parental observations into print in a prominent medical journal (1).

Circa 1997 and 1998 - give or take a few years - considering adverse effects from vaccinations was common and was enacted by researchers, by peer-reviewers, and by editors. For example, the NVICP's Robert E. Weibel, M.D. and colleagues had written a vaccination-effects study published in Pediatrics (23) one month after Wakefield et al 1998 was published in The Lancet (1; February 1998).

Weibel et al titled their study, "Acute Encephalopathy Followed by Permanent Brain Injury or Death Associated With Further Attenuated Measles Vaccines..." and concluded "...that a causal relationship between measles vaccine and encephalopathy may exist as a rare complication of measles immunization", whether from the measles vaccine, the measles-rubella vaccine, or the MMR (23).

Given that studies like Weibel et al 1998 were addressing legitimate concerns and were passing peer-review in prominent journals, Wakefield et al's speculation about possible links between the MMR and a regressive autism subgroup with gastrointestinal pathology was not as egregiously out-of-bounds as Richard Horton and major media would have us believe in 2010.

Part 4: a brief look at Weibel et al 1998

A. Published in March of 1998, the Weibel et al paper was in the pre-publication, peer-review process virtually the same time as was Wakefield et al 1998.

B. After major exclusions intended to eliminate co-factor influences, 48 severe adverse effects from MMR were identified amid NVCIP data.

C. The 48 cases of adverse effects were summarized as follows: "Eight children died, and the remainder had mental regression and retardation, chronic seizures, motor and sensory deficits, and movement disorders." (23) Notice that Weibel et al's summary of findings is remarkably similar to traits described in PDD/NOS!

D. Subsequent reviews of MMR safety often interpret Weibel et al 1998 as showing how rare MMR adversities are.

E. Some MMR analyses cite Weibel et al 1998 as showing that adverse effects of MMR vaccinations are known and can be severe. Indeed, Weibel et al's MMR findings are consistent with more recent analyses, "Statistically significant increases in the incidence of serious neurologic disorders following pediatric MMR vaccine in comparison to DTwcP vaccine were found." (24) and "...there is biological plausibility and epidemiological evidence showing a direct relationship between... measles-containing vaccines and serious neurological disorders." (25)

F. The schedule of vaccinations for children in the U.S. and U.K. has increased dramatically since most years included the the Weibel et al analysis, and this increase has occurred in the absence of studies comparing adverse events in vaccinated and unvaccinated children.

G. Exclusions in Weibel et al 1998 are significant and suggest that the study's 48 severe MMR-related injuries may be the tip of a huge iceberg.

Part 5: Exclusions in Weibel et al 1998

The exclusion criteria used by Weibel and colleagues were important to their study's focus and to the researchers' ability to justify their conclusions. Nonetheless, the study's exclusions and several other factors suggest that Weibel et al's 48 severely injured children may represent a large under-estimation, as suggested by the data of Geier et al (24-25) and as reported by numerous parents including those in the study by Wakefield et al 1998 (1).

A. "Postinfectious encephalopathy complicates approximately 1 in 1000 cases of natural measles and results in a mortality rate of 10% to 20% and permanent central nervous system impairment in the majority of survivors... Case reports and reviews suggest that similar neurologic complications can, less frequently, follow the administration of live attenuated measles vaccine..." (23)

B. From 403 claims submitted to 48 cases included in the study:
        "A total of 403 claims of encephalopathy and/or seizure disorder after measles, MR, MMR, mumps, or rubella vaccination were identified during this 23-year period. Of these claims, 48 (25 males and 23 females) met the inclusion criteria and acquired an acute encephalopathy of undetermined cause 2 to 15 days after receiving measles vaccine, MR, or MMR." (23)

C. Underreporting:
        Weibel et al 1998: "The 48 cases of encephalopathy probably represent underreporting to this passive system, which does not require individuals to file for compensation and requires medical documentation." (23)  "
       FDA summary of reporting: "FDA receives by direct report less than 1% of suspected serious ADRs... This means that cases spontaneously reported to any surveillance program, which comprise the numerator, generally represent only a small portion of the number that have actually occurred." (20)

D. Vaccine Injury Table specifies: In the absence of an alternate cause [co-factors may cloud this issue, see below]
       "For an individual who received a measles, mumps, or rubella vaccine, the act grants, in the Vaccine Injury Table, the presumption of vaccine causation
if the first manifestation of encephalopathy occurs, in the absence of an alternate cause, 15 days or less after receiving any of these vaccines. The injury or its
residual effects, except when death occurs, must persist for >6 months." (23)

E. Exclusion by decree: changing eligibility time period from onset 15 days or less to onset between days 5 to 15, thus excluding MMR-induced deteriorations that began on days 1 thru 4 after the MMR vaccination. In Weibel et al (Figure 1, p 385) 6 of the 48 adverse events began prior to day 5.
       "Effective March 10, 1995, the [NVICP] program changed the time period of a Vaccine Table Injury for these vaccines and the onset of encephalopathy from <15 days to 5 to 15 days..." (23)

F. Abrupt onset included in Weibel et al, thus gradual onset excluded (23): Many parents have reported that their now autistic child's MMR-induced regression began soon after the MMR vaccination but was gradual and continued to develop (adversely) for months after the vaccination.

G. Exclusion of postictal: "Seizures with mental dysfunction attributed to the postictal state or medication were not considered to be encephalopathy." (23) Since chronic seizures were the most common adverse effect of measles, MR, and MMR vaccinations (23), to exclude postictal mental dysfunction seems to have eliminated from consideration neurologic deteriorations induced by seizures.

H. Infectious, toxic, metabolic exclusions: "Cases of encephalopathy were excluded if an infectious, toxic, traumatic, or metabolic cause or a recent exposure to natural measles, mumps, or rubella was identified or full recovery occurred within 6 months." (23)
       These three exclusions in Weibel et al 1998 have enhanced significance in 2010. Etiologically significant co-factors abound. Autism has long been associated with herpes simpex virus and with human herpesvirus 6 (eg, 26-27). Various airborne pollutants are associated with autism (28-30). Various gene alleles related to detoxification and metabolic processes are associated with autism (eg, 31-33). And classic mitochondrial disorders that are clinically silent prior to vaccinations (eg, Hannah Poling) or clinically more common mitochondrial dysfunction (34) also stand as risk factors which may be co-active along with MMR vaccinations - especially if the child's MMR vaccination occurs during the same incident in which a thimerosal-containing vaccine is injected (eg, 35-36). Enforcement of a one-size-fits-all vaccination schedule means that many children with known risk factors are being vaccinated, including with the MMR.

Conclusions: Citations and analysis presented in this brief essay make clear that The Lancet editor has waffled on behalf of future sales of current and new vaccines, that Wakefield et al's 1998 speculation about MMR vaccinations being linked with an autism subgroup were not far afield of other peer-reviewed studies, and - as various researchers have stated - increasing the safety of vaccinations merits ongoing attention. Adverse events happen and need continually be minimized.

Comments in a petition on behalf of physicians Wakefield, Murch, and Walker-Smith are informative (37).


References:

1. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children
Wakefield AJ et al.
Lancet. 1998 Feb 28;351(9103):637-41.
here

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