Wakefield’s article linking MMR vaccine and autism was fraudulent
BMJ 2011; 342 doi: https://doi.org/10.1136/bmj.c7452 (Published 06 January 2011) Cite this as: BMJ 2011;342:c7452All rapid responses
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My son was adversly affected by the MMR at 15 months. His story so mirrors many other parents stories by becoming non-verbal and having dietary, behavioural, learning, sleeping problems. To add to that my son has bowel and gut problems and at the age of 8 started to have seizures. We helped the seizures by going on a g/f and c/f diet plus supplements that he was deficient in. The seizures went away but came back with a vengance at the age of 15.
Now he is on medication to control his seizures but he is not able to get out of bed most days and I worry for his state of mind and health and that is why I am very serious about getting my message across to warn others of the dangers. I waited 14 years to hear my son say "Ma" and he is saying a few words now and can let me know if he wants something or not.
Not all will suffer the way our children did from the adverse effects of the MMR but eventually the population will suffer if we allow un-safe vaccines. My son is 18 now, and I am not anti-vaccine I just want safe vaccines.
Competing interests: Mum of MMR vaccine damaged son
Dr. Tomljenovic's answer to my letter is full of them.
Of course critical analyses of vaccine safety doesn't make one "anti-
vaccine", but speaking on anti-vaccine conferences and uncritically
copying and pasting bad and/or misinterpreted science from anti-vaccine
web sites makes one anti-vaccine.
To publically raise doubt about whether the measles vaccine actually
works, reveals biomedical illiteracy.
Claims like "If you search the literature you will find that outbreaks of
infectious diseases frequently occur in fully vaccinated populations"
identify the anti-vaccine activist, deliberately misrepresenting the
published evidence:
Gustavson et al (http://www.ncbi.nlm.nih.gov/pubmed/3821823) describe
what we know to date: 1xMMR will leave about 5% of vaccinees non-immune
(in this case 4.1%), and "none of the 1732 seropositive students
contracted measles.".
Tugwell et al (http://www.ncbi.nlm.nih.gov/pubmed/14993534) describe
an outbreak of chicken pox with an attack rate of 12% in children
vaccinated once, which is actually in line with the incidence second
varicella infections in patients who previously had the disease
(http://www.ncbi.nlm.nih.gov/pubmed/12042544) and roughly a quarter of the
incidence in unvaccinated children (although there were very few in that
particular outbreak this is what is commonly observed). The 1x varicella
schedule has recently been estimated to have prevented about 50'000
hospitalisations in the US from 2000 to 2006
(http://www.ncbi.nlm.nih.gov/pubmed/21199857).
Both in smaller outbreaks in the US (e.g. 2008 San Diego, 11 cases,
all unvaccinated http://www.cdc.gov/mmwr/preview/mmwrhtml/mm57e222a1.htm)
and larger outbreaks (e.g. 1999/2000 Coburg, Germany, 1200 cases, 1100
unvaccinated http://www.aerzteblatt.de/v4/archiv/artikel.asp?id=39670),
the risk of contracting measles was up to 50 times higher in unvaccinated
children than in vaccinated.
The anti-vaccine arguments of Dr. Tomljenovic have been debunked over
and over again.
Competing interests: I have previously blogged on this issue.
Eileen Nicole Simon writes:
"Thank you, John Stone, for pointing out the paper by Yap et al. on
urinary metabolite differences in autism ... The next step must be to try
to understand how abnormal metabolites affect the brain in a way that
leads to the characteristic disorders of language and social obliviousness
exhibited by children with autism."
That, of course, is one line of enquiry, but rather more relevantly
we have right to ask in the present context how three doctors were
successfully prosecuted for effectively fabricating GI abnormalities in
autistic children when according to this study - which was published
within days of the conclusion of the hearing - virtually all autistic
children have them.
Simon speaks of her sad life as a mother of an autistic child of 48
years. And we can only conclude that the medical and psychiatric
professions will have failed both miserably with their closed minds and
closed ranks.
Competing interests: Autistic son
And I repeat:
Being pro-vaccine safety does NOT make one anti-vaccine.
It would be like saying someone was anti-car if they supported the Toyota
2010 recall of 1.53 million cars (due to a faulty brake master cylinder
seal that potentially could have resulted in brake fluid leakage). Or that
someone was anti-food if they opposed GMO foods.
I am NOT anti vaccine, I am anti bad science.
The reason so many dismiss even the possibility that vaccine can cause
damage is because they believe this to be true. This is religion and not
science.
And to believe the media hypes about the measles epidemic is not
exactly scientific either. Has there been an actual study to show how many
of the children who contracted measles were actually vaccinated and how
many non-vaccinated? If you search the literature you will find that
outbreaks of infectious diseases frequently occur in fully vaccinated
populations [1,2] most likely because vaccines suppress Th1 cellular
immunity which is inherently far more effective against viral infections
[3,4]. This is also the reason why there are increasing efforts to develop
vaccines which stimulate Th1 responses [5,6].
[1] Gustafson TL, Lievens AW et al. (1987) Measles outbreak in a
fully immunized secondary-school population. NEJM 316(13), 771-4.
[2] Tugwell BD, Lee LE, Gillette H, Lorber EM, Hedberg K, Cieslak PR
(2004) Chickenpox outbreak in a highly vaccinated school population.
Pediatrics 113, 3 Pt 1, 455-459.
[3] Makidon PE et al. (2008) Pre-clinical evaluation of a novel
nanoemulsion-based hepatitis B mucosal vaccine. PLoS One 3, e2954.
[4] Israeli E, Shoenfeld Y et al. (2009) Adjuvants and autoimmunity.
Lupus 18:1217-1225.
[5] Geissler M, Tokushige K, Chante CC, Zurawski VR Jr, Wands JR
(1997) Cellular and humoral immune response to hepatitis B virus
structural proteins in mice after DNA-based immunization. Gastroenterology
112: 1307-1320.
[6] Schirmbeck R, Zheng X, Roggendorf M, Geissler M, Chisari FV, et
al. (2001) Targeting Murine Immune Responses to Selected T Cell- or
Antibody-Defined Determinants of the Hepatitis B Surface Antigen by
Plasmid DNA Vaccines Encoding Chimeric Antigen. J Immunol 166: 1405-1413.
Competing interests: No competing interests
It is really very troubling if exchanges in BMJ cannot take place
without flying insults. Admittedly, Catherine Becker's reference to "the
anti-vaccine circus" is somewhat milder that some we have seen here but
what is wrong with articulating concerns about vaccine safety? If the
message is that you are no longer allowed to do it, what insurance could
there ever be about the programme not spinning wildly out of control? And
what is the scientific base, as opposed to its ideological one?
As it is Cochrane tells us very little positive about the safety of
MMR, and nothing in relation to autism:
"No credible evidence of an involvement of MMR with either autism or
Crohn's disease was found."
A statement which is virtually meaningless given that none of the six
autism studies reviewed was rated of low risk of bias, and the Cochrane
paper did not even tackle issues of conflict, many of which were
undisclosed: i.e. on their own account they did not find anything but they
were poor studies ("largely inadequate"). They did approve of the one GI
related study they reviewed but it was paid for and authored by the US
Centers for Disease Control and data subsequently placed out of reach - so
once again conditions institutional bias and absolute opacity pertain [1].
If you cannot report or investigate adverse vaccine events without
scorn and hatred being heaped on you, where are the conditions in which
actual science as opposed to reasons of state can flourish?
[1]
http://www.bmj.com/content/339/bmj.b3658.extract/reply#bmj_el_220537
Competing interests: Autistic son
I recently came across a document that was issued to the government
in 1968, entitled Notes on the use and storage of Measles vaccine (live
attenuated) for routine vaccines.
http://www.scribd.com/doc/31707379/Notes-on-the-Use-and-Storage-of-
Measles-Accine-Live-Attenuated-for-Routine-Vaccination
In section 7 the document clearly states that measles vaccine should
not be given to children under 9 months of age as it fails to immunize
them, instead it should be given to children in their 2nd year of life.
In section 8, the document further states that:
"An interval of three to four weeks should normally be allowed to elapse
between the administration of measles vaccine and any other vaccine,
whichever is given first."
Currently measles is given as an MMR shot (essentially-3 vaccines in
one) at 12-13 months of age. In UK, kids will on the same day also receive
a PCV shot (Pneumococcal). Thus, the UK immunization practices completely
violate the recommendations outlined in the 1968 document.
Not only that, but plans appear to be underway to essentially
vaccinate children against 6 diseases at the same time (Hib/MenC, MMR and
pneumococcal).
http://www.dh.gov.uk/en/MediaCentre/Statements/DH_122026
The UK Department of Health claims that:
"Independent scientific research has shown that providing these
vaccines at the same time is safe, effective and more convenient for
parents."
No reference is quoted. I would REALLY like to see this independent
research.
Competing interests: No competing interests
Lucija Tomljenovic asks why Andrew Wakefield's findings were
duplicated in 5 other countries. The answer is easy:
They were not.
The findings in the since retracted Lancet paper were reported as
follows:
"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."
There has not been an independent verification of this triad of
results, also not in the list Dr. Tomljenovic provides (1), which
comprises case reports, conference proceedings and papers of colleagues of
Wakefield's in journals he edited, as Debajyoti Datta rightly points out
(2).
The case of bowel inflammation in one autistic adult and two
editorials from a time when the extent of data manipulation in the Lancet
paper were still unclear (2000 and 2005) (3) don't "duplicate" Wakefield's
findings and the reference to the Cochrane's 2005 review of the MMR
vaccine (4) is a typical anti-vaccine canard. The topic at hand is whether
MMR causes autism with gut problems - the same Cochrane Review answers
precisely this question:
"No credible evidence of an involvement of MMR with either autism or
Crohn's disease was found."
I was wondering why a post-doctoral fellow, with free access to the
biomedical literature, an associate editor of a biomedial journal herself
(5), with no declared conflict of interest, would indiscrimately copy and
paste from anti-vaccine pages defending Andrew Wakefield, but quickly
found that Dr. Tomljenovic has recently spoken on the same anti-vaccine
conference as Andrew Wakefield (6), which might explain her bias. The
willingness of someone with scientific training to associate with the anti
-vaccine circus is still baffling.
(1) http://www.bmj.com/content/342/bmj.c7452.full/reply#bmj_el_248023
(2) http://www.bmj.com/content/342/bmj.c7452.full/reply#bmj_el_248215
(3) http://www.bmj.com/content/342/bmj.c7452.full/reply#bmj_el_248456
(4) http://www2.cochrane.org/reviews/en/ab004407.html
Competing interests: I have previously blogged about this issue.
Actually the second reference that I cited is easily found as it is
by Nature Publishing Group:
http://www.nature.com/ajg/journal/v100/n4/full/ajg2005166a.html
The American Journal of Gastroenterology (2005) 100, 979-981;
doi:10.1111/j.1572-0241.2005.41202_4.x
Panenteric IBD-Like Disease in a Patient with Regressive Autism Shown
for the First Time by the Wireless Capsule Enteroscopy: Another Piece in
the Jigsaw of this Gut-Brain Syndrome?
"A 28-yr-old male with regressive autism recently came to our
attention with unexplained microcytic anemia requiring intravenous iron
supplementation. Severe constipation with bloating and abdomen distension
and symptoms of gastroesophageal reflux were reported by parents.
Gastroscopy under general anesthesia revealed hemorrhagic gastritis with
inflammatory pseudopolyps that reached the pylorum with a "pearl necklace"
appearance. The biopsies in the stomach and duodenum confirmed the chronic
active inflammation whereas those in the second part of the duodenum were
inconsistent with celiac disease. The whole colon and the terminal ileum
were macroscopically normal at colonoscopy, whereas random biopsies showed
a chronic severe active mucosal inflammation (intraepithelial lymphocytes
and eosinophyls infiltrations and villous focal atrophy with reactive
lymphoid nodular with intraepithelial CD3 and mucosal CD8), compatible
with active IBD. The wireless enteroscopy capsule (GIVEN? Imaging
Diagnostic System), revealed areas of patchy erythema, mucosal erosions,
and ulcers in both jejunum and ileum (Fig. 1A-D). A panenteric IBD-like
disease, consistent with previous descriptions of autistic enterocolitis,
was finally diagnosed."
I also found several editorials which suggest that Andrew Wakefield's
hypothesis should not be discarded. For example:
Nature Publishig Group
The American Journal of Gastroenterology (2000) 95,
2154|[ndash]|2156; doi:10.1111/j.1572-0241.2000.03247.x
Autism and the gastrointestinal tract
"Wakefield et al. (13) are to be congratulated on opening yet another
window onto the ever-broadening spectrum of gut|[ndash]|brain
interactions. Their findings raise many challenging questions that should
provoke further much-needed research in this area, research that may
provide true grounds for optimism for affected patients and their
families."
European Journal of Gastroenterology & Hepatology 2005, Vol 17 No
8
The intestinal lesion of autistic spectrum disorder
"This editorial briefly reviews the significance of lymphoid nodular
hyperplasia in the intestinal tract of children with autistic spectrum
disorder. The distinction between physiological and pathological lymphoid
hyperplasia of the intestinal tract is of importance in the context of a
possible causative link with autism. A primary intestinal lesion may occur
as part of the broad spectrum of immunological disorders to which autistic
children are prone. This could result in increased intestinal permeability
to peptides of dietary origin which may then lead to disruption of
neuroregulatory mechanisms required for normal brain development.
Alternatively, there could be a primary defect in the translocation and
processing of factors derived from the intestinal lumen. These
possibilities deserve further investigation and should not be lost in the
fog of the controversy regarding the role of measles/mumps/rubella
vaccination in the aetiology of autistic spectrum disorder."
As for the alleged safety of the MMR, a simple google search also
reveals a most comprehensive study done on this subject, by the respected
Cochrane Review (October 2005).
Although the review found no significant association between MMR and
autism, Chron disease etc (it did however find that MMR vaccine was likely
to be associated with benign thrombocytopenic purpura, parotitis, joint
and limb complaints and febrile convulsions within two weeks of
vaccination and aseptic meningitis (mumps) (Urabe strain-containing MMR)),
none of the 31 studies included in the review met the Cochrane
Collaboration's methodological criteria.
One of the major conclusions from the Cochrane's 2005 MMR review was:
"The design and reporting of safety outcomes in MMR vaccine studies,
both pre- and post-marketing, are largely inadequate."
http://www2.cochrane.org/reviews/en/ab004407.html
Science should be based on evidence, not dogma.
Competing interests: No competing interests
Thank you, John Stone, for pointing out the paper by Yap et al. on
urinary metabolite differences in autism [1]. The next step must be to
try to understand how abnormal metabolites affect the brain in a way that
leads to the characteristic disorders of language and social obliviousness
exhibited by children with autism.
Yap et al. discuss possible disruption in the tryptophan-serotonin-
melatonin pathway. In my own dissertation research, on long-term effects
of neonatal asphyxia in laboratory rats, we found a male-female difference
in brain serotonin synthesis, and initial growth retardation of male pups
[2]. So many scornful people asked back then how relevant such findings
could be for understanding autism, and I have to admit that both findings
were too non-specific to have any direct bearing on autism.
My son with autism is now 48 years old, and I have spent most of my
sad life trying to understand autism. I have come to realize that the
current scientific obsession with "empirical research" has led to neglect
of important existing evidence in the medical literature. Too much recent
research on autism has produced a smoke screen of "evidence" that leads
nowhere. This is my criticism of research that does not include the
brain.
Understanding the brain systems involved in language development is
what is most important. Note that the language areas of the cortex are
not fully developed until 4 to 5 years after birth [3]. But children
begin learning to speak "by ear" long before that, and a diagnosis of
autism is usually made by the age of 3 or 4.
The article on asphyxia at birth by William Windle in the October
1969 issue of the Scientific American drew my attention to the auditory
system [4]. That was just when I was beginning my graduate studies, and
then I discovered the papers on blood-flow in the brain, and the finding
that circulation and metabolism are greatest in the auditory pathway [5].
Auditory nuclei in the brainstem are exposed to greater amounts of
any potentially toxic substance in the circulation. Asphyxia plus
bilirubin or thimerosal or phenylpyruvic acid or aberrant metabolites from
sulfation deficiency in the liver is double trouble (or more), and likely
to impair an infant's ability to begin understanding speech.
References
[1] Yap IK et al. Urinary metabolic phenotyping differentiates
children with autism from their unaffected siblings and age-matched
controls. J Proteome Res. 2010 Jun 4;9(6):2996-3004.
[2] Simon N, Volicer L (1976) Neonatal asphyxia in the rat: greater
vulnerability of males and persistent effects on brain monoamine
synthesis. J Neurochem. 1976 May;26(5):893-900.
[3] Moore JK. Maturation of human auditory cortex: implications for
speech perception. Ann Otol Rhinol Laryngol Suppl. 2002 May;189:7-10.
[4] Windle WF. Brain damage by asphyxia at birth. Sci Am. 1969
Oct;221(4):76-84.
Competing interests: Mother of a son with autism
Constructive discussion
Dear Sir,
May I suggest some useful quotes which might contribute to
constructive discussion:
Cooper LZ, Larson HJ, Katz SL. Protecting public trust in
immunization. Pediatrics 2008;122(1):1-5.
"In fact, there is no more dramatic documentation of the shortfalls
in research on immunization safety than the findings of a series of
Institute of Medicine review committees. At the request of the Department
of Health and Human Services (DHHS), these expert review committees were
established to evaluate specific hypotheses about harm from vaccines. Over
the past 15 years, more than half of the allegations reviewed by the
committees have concluded that "evidence is inadequate to accept or reject
a causal relationship."
Blume S. Anti-vaccination movements and their interpretations.
SocialScience & Medicine 2006;62(3):628-42.
"A crucial finding of Pilgrim and Roger's study bears on the attitude
of professionals and their apparent resistance to the idea of parents
wishing to make their own informed choices. Professionals seem frequently
to have been seen as an obstacle to informed choice, rather than a source
of advice and information. In other words, vaccination may be voluntary in
theory, but that is not how most health professionals treat it in
practice. The information literature they are given, in the view of these
parents, reflects this same point of view: not designed to inform but to
induce conformity. Full of glossy pictures, propaganda, nothing whatever
on possible risks or side effects, on the duration of protection, on
systemic effects on the child's immune system. It is of no help in trying
to make a personal decision since that isn't its purpose: something
particularly resented by highly educated parents accustomed to making
reasoned decisions in most aspects of their lives. The social pressure
exerted on parents who ask awkward questions, trying to reason things out
for themselves, is deeply resented" p.637
(So too it seems are doctors, asking awkward questions, deeply
resented...)
"To focus attention on vociferous opponents of vaccination, and to
expound ways in which they can be countered (e.g. Leask & McIntyre,
2003) is to unite public health and medical professionals behind a banner
of reason and rationality. At the same time it diverts attention from
other sources of dissatisfaction. The unwelcome alternative is to raise
serious, complex and potentially disruptive questions regarding the ways
in which medical professionals behave: a critique that, as we saw, was
indeed articulated by mothers interviewed in both Britain and the
Netherlands." p.639
"Decades of emphasis on personal rights and responsibilities have
encouraged growing number of educated parents, many of whom have already
learned to express their preferences in opting for natural childbirth for
example, to reason for themselves. For such parents the vaccination
literature available and the attitudes of practitioners are deeply
dissatisfying. Rogers and Pilgrim come to a similar conclusion. They point
to a contradiction between the NHS policy emphasis on patients' rights to
informed consent and practices around vaccination that fail to respect
those rights. What we then see is an ideological conflict at the very
heart of public health, in which individual rights on the one hand, and
the expert articulation of the common good on the other, are pitted one
against the other." p.639
"Until recently the tendency was to assume that parental doubts have
no basis in fact and therefore do not merit serious consideration. There
was no interest in the possibility that resistance to vaccination might
follow rationally either from reasonable beliefs or justifiable concerns.
''Where consideration has been given to parents' views they tend to be
portrayed as irrational or driven by neurotic anxiety,'' wrote Rogers and
Pilgrim in 1994. Today, still, some are convinced that anti-
vaccinationists are simply misinformed and irrational (or anti-rational).
They must be made to see the truth of the matter. If their claims
regarding vaccine risks can no longer be ignored, then they must be
addressed and rebutted by appeal to a superior science. Not only is this
sociologically inadequate, it is unlikely to have the desired effect
either. 'Sociologically inadequate' because a sociological analysis must
see both sides as mutually engaged in a process of contestation, in which
the reflexive analysis of (shared) experience, differences in the
assessment of risk, and the place of expertise in democratic decision
making are all at stake. 'Ineffective' because what is being contested
goes far beyond establishment of some objective measure of vaccine-risk,
to the heart of modern citizenship and democratic politics." p. 640
"Concordance in immunization policy, he writes, ''must mean more than
evidence-based health care simplistically interpreted.'' It should mean
''not only applying the evidence to the individual, but also dialogue
between perspectives based on different views of the world. It means an
exchange of views and mutual respect between these very different views''
(Vernon, 2003). He recognizes how great a step this will be for the health
professions. Could dialogue based on ''mutual respect'' produce the
desired effects?"
p.640
I repeat Blume's question: ...."Could dialogue based on ''mutual
respect'' produce the desired effects?"....
Hilary Butler.
Competing interests: Toothcombing bad science is an addictive hobby.