Issues - Chemical Abuse of Children - MMR debate and autism
A Briefing Note by David Thrower April 2002
Part A: A Novel Syndrome
1. What Is Acquired Autism/Autistic Enterocolitis
2. The New Syndrome
3. Recognised Adverse Reactions to MMR
4. Contraindications To Receiving MMR
5. Families Taking Legal Action
6. The UK Department of Health’s Position
7. The Parents Have Seen What They’ve Seen.....
Part B: The Costs of Autism
8. The Financial Costs - Autism Is Costing Billions
10. Failure to Monitor Increases In UK Autism Numbers
11. "Now Almost Everyone Knows Someone Who’s Autistic"
12. University of Cambridge Research
13. University of Sunderland Research
14. National Autistic Society Estimates
15. Report by Fiona Loynes for UK All Party Parliamentary
Group, Dec. 2001
16. Is Autism Increasing? - Some Recent Official UK Pronouncements
17. Autism In The USA
19. New Jersey
Part C: Studies That Have Been Used To Disprove An MMR/Autism
20. Stokes et al paper, Journal of American Medical Association
(JAMA), Oct. 1971
21. Study by Peltola and Heinonen, Lancet, April 1986
22. Paper by Miller, Miller et al, The Practitioner, January
23. Gillberg Study, Sweden, British Journal of Psychiatry,
24. Commentary by Gillberg and Heijbel, Autism, 1998
25. Letter by Fombonne, Pediatrics, March 1998
26. UK Committee on Safety of Medicines Study, June 1999
27. Paper By Taylor, Miller and Farrington, Lancet, June 1999
28. Paper by Miller & Farrington to US Government Reform
Committee, April 2000
29. Patja, Peltola et al Study, Finland, Pediatric Infectious
Disease Journal Dec. 2000
30. Kaye, Melero-Montez and Jick Study, British Medical Journal,
31. Fombonne Paper, Pediatrics, January 2001
32. Dales, Hammer and Smith Study, JAMA, March 2001
33. De Wilde, Carey & Richards Study, Br. Journal of General
Practice, March 2001
34. Davis et al study, Archive Pediatrics Adolescent Medicine,
35. Further Paper by Farrington, Miller and Taylor, Vaccine
36. Fombonne & Chakrabarti Study, Pediatrics, October
37. Further Paper by Taylor, Miller et al, BMJ.com, February
Part D: Reviews That Conclude There Is No Evidence Of A Link
38. Medical Research Council Ad-Hoc Review, March 1998
39. Presentation by Miller to UK All Party Parl. Group on
Primary Health Care, 2000
40. Medical Research Council Sub-Committee Report, March 2000
41. Review by US Institute of Medicine, 2001
42. Elliman, Bedford and Miller Review, Arch. of Diseases
in Childhood, Oct. 2001
43. Medical Research Council Review, July-December 2001
44. Further Review by US Institute of Medicine, February 2002
Part E: The MMR Original Safety Trials Debate
45. Wakefield & Montgomery "Through A Glass Darkly"
MMR safety-studies paper
46. Dr. Peter Fletcher Commentary, Journal of Adverse Drug
47. Dr. Stephen Dealler Commentary, Journal of Adverse Drug
48. Dr. F. Edward Yazbak Commentary, Journal of Adverse Drug
49. The Wakefield/Watson/Shattock Rebuttals
50. The UK Department of Health’s Repudiation of "Through
A Glass Darkly".
Part F: Studies/Papers That Point Towards An MMR Link
51. Paper by Eggers, Klinical Paediatrics, March 1976
52. Weizman, Weizmann, Szekely et al Study, Am. Journal of
Psychiatry, Nov. 1982
53. Delgiudice-Asch and Hollander Study
54. Fudenberg paper
55. Paper by Dr. Reed Warren
56. Warren and Singh Study, Immunogenetics, 1992
57. Singh, Warren, Odell, Warren and Cole Paper, March 1993
58. Singh, Warren, Odell et al Study, Brain Behaviour, March
59. Oleske and Zecca paper
60. Binstock paper
61. Anne-Marie Plesner Letter, Lancet, February 1995
62. Gupta, Aggarwal and Heads Study, Journal of Autism and
Dev. Disorders, 1996
63. Montinari, Favoino and Roberto paper, Naples conference
64. Auwaerter and Griffin paper, Clinical Immunology and Immunopath.,
65. Cook, Courchesne et al Paper, Molecular Psychiatry, May
66. Griffin and Hussy Study, Journal of Infectious Diseases,
67. Martinez et al Study, Proceedings of National Academy
of Sciences, 1997
68. Paper by Zecca, Graffino et al, Meeting of National Inst.
of Health, Sept. 1997
69. Weibel, Caserta and Evans Study, March 1998
70. Wakefield et al "Early Report", Lancet, February
71. Paper by Montgomery, Morris et al (publication date/details
not yet known)
72. Sabra, Bellanti and Colon letter, Lancet, July 1998
73. Further Unpublished Paper by Singh and Yang, October 1998
74. Uhlmann, Sheils et al Paper
75. Bitnun et al Study, Clinical Infectious Diseases Journal,
76. Paper by Dr. Singh to the US Committee on Government Reform,
77. O’Leary Paper Presented to US Congressional Oversight
Committee, April 2000
78. Kawashima, Takayuki et al Study, Digestive Diseases and
Sciences, April 2000
79. Hagenbuch, Kullak-Ublick et al Study, Journal of Pharm.
Exp. Ther., July 2000
80. Wakefield et al Paper, American Journal of Gastroenterology,
81. Statement by Professor Walter O. Spitzer, December 2000
82. Furlano, Anthony et al Study, Journal of Pediatrics, 2001
83. Study by Jyonouchi, Sun and Le, J. Allergy & Clinical
Immunology, Feb. 2001
84. Study by Jyonouchi, Sun and Le, J of Neuroimmunology,
85. Paper by Spitzer, Aitken et al, Journal of Adverse Drug
Reactions & Tox., 2001
86. Paper by Dr. Ken Aitken to the Scottish Society for Autism,
87. Paper by Imani and Kehoe, Clinical Immunology, September
88. Paper by Dr. Timothy Buie, Oasis 2001 Conference for Autism,
89. Paper by Uhlmann, Wakefield, O’Leary et al, J. of
Clinical Pathology, Feb. 2002
90. Paper by Singh and Nelson, February 2002
Part G: Other Potentially Relevant Papers
91. US Developmental Delay Registry Report, 1994
92. Stratton et al Study, National Academy Press, 1994
93. Paper by Carbone.
94. Iizuka, Saito et al Study, Gut, May 2001 (Mumps Study)
95. Statement by Spitzer, US House of Repres. Govt Reform
Committee, April 2001
Part H: Future Papers Investigating A Link
96. Fombonne et al Study, London
97. Charman et al Study, London
98. Study by Professor Andrew Hall, London
99. Study by Takahashi et al, Tokyo
100. Study by Byrd et al, M.I.N.D. Institute, University of
California at Davis
Part J: The Thiomersal Issue
101. Thiomersal’s Possible Role
102. Thiomersal In Vaccines: Statement of US AAP/Public Health
Service, July 1999
103. UK Vaccines With Thiomersal
104. Scientific Review by US Centre for Disease Control, Simpsonwood,
105. Press Release by Waters and Kraus, March 2002
106. UK Medicines Control Agency Position
Part K: Flawed UK Regulatory and Monitoring Systems
107. Fighting Measles, Missing Autism, Overlooking Damage?
108. Has the Medicines Control Agency Missed the Syndrome?
109. UK Department of Health Re-Launch of MMR, January 2001
Part L: UK and US Political Initiatives
110. UK House of Commons Health Committee, Westminster
111 UK All Party Parliamentary Group on Autism, Westminster
112. Scottish Parliament, Edinburgh
113. UK Liberal Democrats
114. UK Conservatives
115. US House of Representatives Government Reform Committee
Part M: Some Conclusions and Some Unanswered Questions
116. Some Broad Conclusions
117. Some Unanswered Questions
This note - which has been put together by the parent of a
child who became autistic after immunisation - sets out the
concerns of parents whose children have degenerated into an
acquired-autistic state after MMR or measles vaccines.
It does not attempt to cover every single piece of the available
scientific literature for or against an MMR/autism link, but
it reviews about 70 of the most recent, most pivotal, or most
frequently-quoted studies and papers.
Its key finding is that there has not been a single credible
study that can robustly refute the claims of the parents that
their children’s acquired autism has been caused by
MMR or related vaccines. Each of the studies that seeks to
"disprove" an MMR/autism link can be argued to be
flawed in design or ambiguous in results. These flaws are
discussed in detail in the text.
It also notes that all but one of the studies that seek to
disprove an MMR/autism link did not look at the actual children
themselves, but rather were based upon statistical analyses
of the medical records of the wider population. Such epidemiological
studies are not appropriate to the identification of relatively-rare
Such studies also fail to address the problem - what was it
that damaged the specific children whose parents are now taking
action through the UK High Court?
The one study that has both claimed there is no MMR/autism
link and also actually looked at a sub-set of the damaged
children was unable to prove or refute the suggested association
with MMR on the basis of the information available - although
it went on, despite this, to insist that MMR was safe.
Parents who have scrutinised the studies quoted by the Department
of Health as "proof" of there being no link have
found that such studies crumble easily when pressed. To give
just one example, the Finnish study by Patja, Peltola et al
was very loudly heralded at the start of 2001 by the Department
of Health as convincing and conclusive proof that MMR was
safe. After intense critical scrutiny by parents and media,
by the end of 2001 the Medical Research Council was forced
to admit that Patja, Peltola et al’s original 1998 paper
"did not examine the relationship of MMR and autistic
spectrum disorders.....and does not therefore provide useful
evidence on this point." Of the later 2000 paper by Patja,
Peltola et al, the MRC admitted: "The findings need to
be interpreted with some caution, as cases of autistic spectrum
disorder or bowel disorders not considered at the time attributable
to MMR would not necessarily have been reported". Quite
In contrast, the parents find that there are a number of studies
that suggest that MMR could be causing acquired autism (or
"autistic enterocolitis") in significant numbers
Not all of these studies originate from only one group of
researchers, as has sometimes been asserted by those who defend
MMR. The studies that point to a link have involved a growing
number of research teams, in several countries. Other studies,
whilst not specifically targeting MMR, offer further clues
as to what may be happening, and are consistent with an MMR
Furthermore, many of the studies that suggest that there is
an MMR/autism link are based upon the scientific analysis
of data gathered from detailed individual medical examination,
and upon medical samples taken from the children concerned.
These are the studies that actually seek to address the two
key questions, "what is the damage sustained by this
specific child, and what exactly precipitated the damage to
this specific child?".
A "house of cards" has thus been constructed by
the UK Department of Health over the past five years, with
repeated assurances being given to the public, but with these
being based upon a lop-sided, partisan and selective gathering
and interpretation of the available evidence.
This briefing note also finds that there are other related
concerns - from the regulatory bodies themselves - about the
risk of permanent developmental damage from thiomersal-containing
vaccines, though it is not yet clear whether these problems
are directly interlinked biologically to the MMR/autism problems
(MMR does not contain thiomersal). Class-action lawsuits are
now under way in the US over thiomersal and autism, just as
they are in the UK over MMR and autism.
Although complete and precise scientific proof of how the
children have been damaged by vaccines and become autistic
is still emerging, there have been numerous vital clues over
the past five years or more - clues that all too often have
been ignored, or, worse still, rejected out of hand, by the
The medical establishment has repeatedly asked itself the
wrong question. It has asked itself "Is MMR safe?",
hoping for an affirmative answer. In contrast, researchers
and parents have asked two very different questions: "What
is wrong with this child?", and "Why did this child
change from being healthy to being autistic?". It is
answering these latter two questions that should be the key
The children that have been damaged have had their lives ruined.
They were previously healthy. They now have seventy or eighty
years of mental handicap ahead. Whether their sacrifice is
justified in the interests of wider public health is not the
point at issue.
Finally, this briefing note poses a number of unanswered questions
about MMR, and about the UK children that are believed to
have been severely damaged by its administration
Autism is not an illness in itself, so much as a manifestation
of a dysfunction in certain parts of the central nervous system,
particularly affecting language, cognitive and intellectual
development and the ability to relate to others.
The "classic" form of autism was first described
by Dr. Leo Kanner. These children were different from normally-developing
children from birth.
However, a very different form of autism has now begun to
predominate. In this, children develop normally, passing all
their developmental milestones, and then later acquire an
autistic-like condition. They lose their previously-demonstrated
speech, learned behaviour and social skills. In effect, they
dissolve into a state of mental impairment, of varying severity.
Often the damage is severe or very severe, and usually the
damage is permanent.
This late onset of autism typically follows the receipt of
MMR vaccination. It does not necessarily occur immediately
afterwards - onset of autism is not in any case an "acute"
reaction - and there are now grounds for believing that onset
following vaccination may be very gradual indeed, spread over
at least many weeks, more probably several or many months,
or even in some cases several years.
Crucially, the onset of this acquired form of autism is accompanied
by other visible manifestations of problems. These include
bright red ears and dark rings under the eyes after certain
foods, gluten and casein intolerances, hyperactivity, night
sweating and loss of temperature control, and chronically
poor sleep patterns.
The arrival of these problems and the degeneration of the
child into autism as a "package" strongly suggests
that they are interconnected
The timing of onset following vaccination is described by
the UK Department of Health as a coincidence. Their argument
is that it is "noticed" around this time, because
this is a time when child development is most rapid, and any
failure most noticeable.
However, very significantly, much older children have also
degenerated into autism after MMR. If degeneration in affected
children always follows immunisation with MMR or measles-containing
vaccine, regardless of the age of the child, then it implies
that the link is not coincidental.
Also, no cases are known, at least to campaigning parents,
of any children who have become autistic just before MMR.
Also, it is not simply a failure to develop. The children
have developed normally, then inexplicably acquired their
autistic state. This protracted event has been directly observed
by parents and relatives, and in many cases recorded on photographs
and video footage.
No credible alternative explanation for why a previously-healthy
child should become severely autistic has been put forward.
The unheralded acquisition of a state of severe disability,
in a substantial number of hitherto-healthy children, has
to have a significant causal trigger.
Undoubtedly there are other factors involved, pointing to
a predisposition of certain children to be vulnerable to damage,
of varying severity. Research should be trying to pinpoint
those factors, but is not. It is being held up by the refusal
of the medical establishment in the UK to recognise the problem,
or even to recognise the increase in autism.
Also coinciding with the late onset of autism in many of the
children (or other damage - autism is not the only manifestation
of there being a problem), has come gastrointestinal problems
such as alternating bouts of diarrhoea and constipation, chronic
abdominal pains and bloating.
Examination of children has identified a novel form of inflammatory
bowel disease, ileal-lymphoid nodular hyperplasia. This has
emerged after ileocolonoscopy of affected children and analysis
of samples. This research has not only come from the Royal
Free Hospital, London, but also from other centres in the
The simultaneous onset of these problems after a normal early
development suggests that it is highly likely that these other
elements are linked into the biological explanatory sequence
of autism, notably through the pathway of gut damage and either
the penetration of the blood-brain barrier or the triggering
of some other process, such as serious myelin damage (in basic
terms, the myelin sheath is the "insulation" around
the neurons or "wires" of the brain).
This is a summary of the new syndrome of autistic enterocolitis:
In a 200-strong cohort of children examined through ileocolonoscopy
at the Royal Free Hospital, London, an almost 100% incidence
of ileal-lymphoid nodular hyperplasia has been found. This
condition manifests itself as swollen lumps throughout the
intestinal tissue of autistic children. The condition is very
rare in non-autistic children.
The condition is believed to have developed in each case in
the period following MMR immunisation
Because of its swollen and hyperplasic condition, undigested
toxins , having not been stopped by either the intestine or
the liver (which can also be damaged) may then be able to
attack the central nervous system. The evidence for the complete
pathway of damage is uncertain at present, due to lack of
An alternative pathway of damage may be that the virus(es)
in the vaccine, or other constituents of the vaccine, may
be inflicting the actual damage, or interfering with the brain’s
further development by damaging myelinisation. Comprehensive
studies to determine this have also yet to be undertaken.
It is also possible that thiomersal, a mercury-based preservative
that has been routinely used in a number of vaccines, may
have played a role. Again, adequate research has not yet been
Damage may in the event be via a combination of these pathways.
As a background to the controversy about MMR’s safety,
it is important to make clear that there is already a range
of adverse reactions to the vaccine that are recognised by
the manufacturers themselves, if not by the UK Department
of Health. The latter insists that the vaccine is safe and
has a good safety record worldwide. However, the February
2000 edition of the manufacturer’s notes, issued by
Merck & Co., lists the following possible adverse reactions
reported during clinical trials:
(body as a whole) panniculitis, atypical measles, fever, syncope,
headache, dizziness, malaise, irritability
(cardiovascular system) vasculitis
(digestive system) pancreatitis, diarrhoea, vomiting, parotitis,
(endocrine system) diabetes mellitus
(hemic and lymphatic system) thromobocytopenia, purpura, regional
(immune system) anaphylaxis and anaphylactoid reactions, angioneurotic
edema, bronchial spasm
(musculoskeletal system) arthritis, arthralgia, myalgia
(nervous system) encephalitis, encephalopathy, measles inclusion
body encephalitis (MIBE), subacute sclerosing panencephalitis
(SSPE), Guillain-Barre Syndrome, febrile convulsions, afebrile
convulsions or seizures, ataxia, polyneuritis, polyneuropathy,
ocular palsies, paresthesia. On encephalitis, the Merck notes
state that "the data suggest the possibility that some
of these (reported) cases may have been caused by measles
(respiratory system) pneumonitis, sore throat, cough, rhinitis
(skin) Stevens-Johnson syndrome, erythema multiforme, urticaria,
rash, burning/stinging at injection site, wheal and flare,
redness, swelling, induration, tenderness, vesiculation at
(special senses - ear) nerve deafness, otitis media
(special senses - eye) retinitis, optic neuritis, papillitis,
retrobulbar neuritis, conjunctivitis
(urogenital system) orchitis
(other) "death from various and in some cases unknown
causes has been reported rarely following vaccination with
MMR; however, a causal relationship has not been established"
The above, although qualified in Merck’s preamble as
being "without regard to causality", does suggest
that rare or relatively rare serious adverse events are not
unknown and are already recognised by the manufacturers of
MMR. In this context, the possibility of an unrecognised adverse
event such as autism - particularly if its onset is insidious
- becomes rather more credible.
This list of potential contrainications to receiving MMR,
contained in the Merck manufacturer’s information sheets,
is also lengthy. It is very questionable as to whether all
parents of UK recipients of MMR during the late 1980s and
the 1990s were questioned in detail on these aspects before
their child received MMR: Contraindications include:
Hypersensitivity to any component of MMR, including gelatine
Anaphylactic or anaphylactoid reactions to neomycin
Febrile respiratoty illness or other active febrile infection
Patients receiving immunosuppressive therapy
Individuals with blood dyscrasias, leukemia, lymphomas of
any type or other malignant neoplasms affecting the bone marrow
or lymphatic system
Primary and acquired immunodeficiency states, including patients
who are immunosuppressed in association with AIDS or other
clinical manifestations of infection with human immunodeficiency
Patients with cellular immune deficiencies or hypogammaglobulinemic
and dysgammaglobulinemic states. The Merck information sheets
note that "Measles inclusion body encephalitis (MIBE),
pneumonitis and death as a direct consequence of disseminated
measles vaccine virus infection has been reported in immunocompromised
individuals inadvertently vaccinated with measles-containing
Individuals with a family history of congenital or hereditary
immunodeficiency, until the immune competence of the potential
vaccine recipient is demonstrated
Some of the above contraindications could be partly relevant
to the MMR/autism issue. And clearly, if a hitherto-unrecognised
syndrome such as the insidious onset of autism, should exist
but go unreported, then the list of contraindications would
remain too narrowly defined until the syndrome became recognised.
Much therefore depends on the effectiveness of reporting systems
and length of follow-up. These issues will be covered later.
Between 2,000 and 3,000 families whose children became autistic
or had other serious adverse events after MMR are believed
to be now taking legal action, or actively seeking to take
legal action, in the UK, against MMR manufacturers Aventis
Pasteur MSD Ltd, Merck and Company Inc, SmithKline Beecham
& French Laboratories Ltd and SmithKline Beecham Plc.
The trial date is currently fixed for October 2003 in the
High Court of Justice in London.
Leading UK legal firms involved are Alexander Harris, Freeth
Cartwright Hunt, and Hodge Jones & Allen. The action is
being brought under the European Union’s Product Liability
Directive, the Consumer Protection Act.
Cases include children who received Aventis Pasteur MSD’s
Immravax and Glaxo SmithKline’s Pluserix brands of MMR
vaccine. These brands were withdrawn by the UK Department
of Health in 1992, two years after a similar vaccine containing
the Urabe strain of mumps virus was withdrawn in Canada, following
reports of meningitis.
The UK lawyers Alexander Harris have stated that a clear pattern
of events began to emerge when they were contacted by families,
with children who had been developing well, both physically
and intellectually, before the MMR vaccine, then acquired
their autistic state after the vaccine. This condition was
often accompanied by other symptoms, with sometimes only a
gradual decline into autism. Many of these children are now
chronically ill and mentally or physically disabled.
By 2002, the number of UK cases of alleged damage by MMR was
growing rapidly, with an increase of well over a hundred cases
in the space of a few weeks.
A class action over autism is now also under way in the US,
led by a large consortium of specialist lawyers. This action
is based upon autism and other damage being caused by thiomersal,
a mercury-based preservative. This is used in some vaccines,
but reportedly not MMR. However, as noted, it is possible
that damage caused by MMR and damage caused by thiomersal
may be interlinked biologically.
The initial US lawsuit was filed by Walters & Krauss (Long
Beach, California). Other law firms taking action are Anderson
& Krieger (Temecula, California), Dogan & Wilson ((Pascagoula,
Mississippi), Doran & Murphy (Buffalo, New York), Evert
& Weathersby (Atlanta, Georgia), Hendrickson & Long
(Charleston, West Virginia), Jones, Martin, Parris & Tessener
(Raleigh, North Carolina), Leach, Schwarz & Strassberg
(Bala Cynwyd, Pennsylvania), Martzell & Bickford (New
Orleans, Louisianna), and Wise & Julian (Alton, Illinois).
More firms are expected to become involved.
The US defendants are Aventis Pasteur Inc., Pfizer Inc., Glaxo
SmithKline, Merck and Co., Abbott Laboratories, American Home
Products, Baxter International Inc., Eli Lilly & Co.,
Sigma Chemical Co. and Aldrich Chemical Co.
It is also noteworthy that there is a legal precedent for
autism being triggered by multiple vaccination, even if not
by measles-containing vaccine. In the United States Court
of Federal Claims, in the case of Eric Lassiter v. Secretary
of the Department of Health and Human Services, in a judgement
filed on December 17th 1996, a case of autism was successfully
brought by the parents of Eric Lassiter. The decision of entitlement
was as follows:
"This case arises under the National Vaccine Injury Compensation
Program. Petitioner’s mother, Mrs. Mary Lassiter, filed
this claim on behalf of her son on September 26th 1990, alleging
that as a result of the administration of a diptheria-pertusis-tetanus
(DPT) shot on April 19th 1972, the petitioner sustained an
injury set forth on the Vaccine Injury Table (s14 of the Act),
namely an encepalopathy, with permanent neurological damage.
Respondent defends by arguing that because no contemporaneous
medical records exist that document conclusively that the
onset of the injury occurred within the requisite time frame,
petitioner has not established a Table injury. Respondent
argues further that petitioner’s condition, more likely
than not, is due to autism and is unrelated to the DPT vaccine.
Following a careful review of the record in its entirety,
the Court concludes that Eric Lassiter is entitled to compensation."
The judgement also included the following paragraph:
"A careful interpretation of the literature indicates
that autism can be mirrored by a condition that includes "autistic-like"
signs or symptoms. Eric’s condition has never been diagnosed
conclusively as autism according to the medical records. The
predominating diagnosis refers instead to "static encepalopathy
with autistic tendencies in addition to delayed development"".
The judgement concluded:
"In summary, respondent’s (Department of Health
& Human Services) evidence and proffered explanations
are weak, unconvincing and insufficient to support a finding
of an underlying metabolic or genetic disorder as the cause
of Eric’s affliction. Petitioner (Lassiter) has presented
a better case in support of a Table injury. The Court concludes
that a preponderance of the evidence requires a finding for
Despite research pointing to an original failure to properly
conduct safety tests with adequate follow-up of MMR (see later),
and emerging research linking MMR with autism (autistic enterocolitis
syndrome) and/or inflammatory bowel disease, the UK Department
of Health and other medical institutions continue to insist
that MMR is safe
This claim is based upon advice of the UK Committee on Safety
of Medicines and Joint Committee on Vaccination and Immunisation
- both of which would suffer a catastrophic loss of public
confidence, should such a link emerge - and a number of studies,
all of which arguably have severe methodological weaknesses
or inconclusive outcomes. Details follow later in the text.
Much of the support for MMR, and denial of a link with autism,
is based around a very small number of these studies, which
the various sectors of the medical establishment have then
There have also been general reviews of the MMR/autism issue
by the Medical Research Council, most recently in late 2001,
and by other bodies. These reviews have failed to find a link
between MMR & autism. The parents believe this failure
was inevitable, given the past lack of funded research into
causes, and the superficial nature of these reviews, which
have accepted "absence of evidence" as "evidence
of absence" of a link.
The outcome of these reviews, and other published papers,
has then been misrepresented or misinterpreted by the Department
of Health as hard evidence that there is not a link.
The DoH-sponsored impression of "a growing body of evidence"
that there is no MMR/autism link is therefore illusory - the
"house of cards".
The Department of Health’s position on MMR has been
endorsed by many of the major medical institutions, though
it is questionable whether these institutions have themselves
fully considered, in adequate detail, all the evidence on
both sides of the argument.
It is also unlikely that any of these bodies has met with
parents or listened sufficiently attentively to their accounts
of how their children degenerated. It is likely that some
of the bodies, and spokespersons, backing MMR and refuting
a link with autism are entirely basing their confidence upon
a few selected studies, and that their knowledge of the actual
children believed to have been damaged is very poor. Their
detailed knowledge of the studies that point towards there
being a problem may be weak and incomplete.
The starting point should be to listen to the patient. Most
of those giving reassurance have never even met the patient,
nor the patient’s parents, nor examined the affected
child, nor reviewed their medical case-notes.
Despite the DoH’s position of "MMR or nothing"
(and increasing numbers of parents seem to be choosing the
latter), when MMR was introduced in 1988, the UK National
Health Service advice to doctors was that single vaccines
should be made available for any parents not wishing their
child to have MMR.
In the pamphlet, Immunisation Against Infectious Disease",
which accompanied the introduction of MMR to the UK, it stated:
"For children whose parents refuse MMR vaccine, single
antigen measles vaccine will be available" (source: Joint
Committee on Vaccination and Immunisation, 1988). It is unclear
when, or why, this advice was withdrawn by the DoH, but it
may have followed discontinuation of the single vaccines as
an economy measure.
During the years 1998-2002, a one-sided view of the MMR/autism
issue has thus been adopted by the Department of Health and
its satellite organisations, much of it aimed at restoring
public confidence in immunisation, to fight communicable diseases,
rather than rigorously searching-out the cause of the damage
to the actual children. Fresh publicity issued during early
2002 took a one-sided view of the debate, and ignored some
key scientific evidence such as the January 2002 research
by Dr. Vijendra Singh (see later), despite the latter being
widely available in advance of the date of the Department’s
A similar denial process has occurred in the US, but its main
roots lie in the UK, and based on (mainly statistical) advice
stemming from only a very small number of sources.
At the end of 2001, the UK Department of Health released a
"Top 10 Truths/Top 10 Myths" leaflet about MMR,
and this is summarised below, with a critique alongside:
(UK Department of Health’s "Top
|(Department of Health "Truth")
||(Critical Response of Parents)
|MMR is safest way to protect children
||Does not address the alleged damage
|Over 500m doses of MMR have been used in over 90 countries
||Almost all those countries have no autism database.
|Only US has good data
||- and this shows a steep rise in autism
|No country in the world recommends single vaccines
||No country in the world has yet acknowledged that there
may be an MMR/autism link, either, but that may yet follow
in time. Some countries permit single vaccines as a choice.
|Children who are not immunised with MMR increase the
chance of infection in others.
||True. But those children could still receive single
vaccines. And there may yet be a massive loss of confidence
in all vaccination, if the children win in the High Court.
It would therefore be prudent to think of this possibility,
and permit choice now.
|The evidence is that MMR does not cause autism or IBD
(a number of studies are quoted, but only those which
suit the Department’s stance)
||There is evidence that suggests that it may do. Every
one of the quoted studies that "disproves" an
MMR/autism link can be flawed (see elsewhere in this document).
|Wakefield et al in 1998 said "We did not prove
||True. The research is still unfolding. Time did not
stop in 1998.
|Single vaccines put children at risk The Department’s
argument is based upon a supposition that some children
would not complete the full course of vaccines.
||But if the children win in the High Court, and the Department
is shown to have misled the public (either unknowingly
or knowingly), the damage will be far greater. And already,
some children are avoiding any measles vaccine. The Department’s
argument is already having a perverse consequence, and
may eventually massively backfire.
|MMR was thoroughly tested before introduction into the
UK in 1988.
||In the context of adverse outcomes with an insidious
long-term onset, MMR was not properly tested. Advice at
the time to explore possible adverse effects was not followed
up. By disputing historical facts, the Department reveals
|Two doses of MMR are needed to protect children.
||The efficacy of MMR in terms of preventing measles is
not the point at issue.
|There are very few children with genuine contraindications.
||This does not address the MMR/autism link. It also does
not square with the manufacturer’s own information
sheets, which imply a substantial number of possible adverse
|The Department of Health’s "Top 10 Truths"
leaflet ends with the reassuring statement, "All
of the above are correct"!
||The above critique suggests that the "truth"
is nowhere near clear-cut, and the Department’s
position is thus exposed as artificial and one-sided.
of Health’s "Top 10 Myths")
|(Department of Health "Myth")
||(Critical Response of Parents)
|Getting protection by catching the disease is better.
||This is not the issue in dispute.
|Three viruses given at the same time is too much for
||It may yet prove to be. The Department has no evidence
(in the context of the MMR/autism debate) to the contrary,
in relation to live viruses.
|Other countries recommend that MMR is given as separate
||Of course they don’t. Perhaps this is because
no country has yet woken up to the problem. As yet, there
is insufficient evidence to alter this position.
|Measles, mumps and rubella are rare in the UK so there
is no need to immunise.
||This is not the issue in dispute.
|MMR causes autism and bowel disease. There is evidence
pointing towards an MMR/autism/IBD connection. Until this
area is thoroughly researched, it is scientifically untenable
to rule it out.
||There was a scientific paper that linked MMR and autism/IBD
There have now been a number of such papers. They form
part of an unfolding story.
|Giving MMR as separate vaccines reduces the risk of
||It is not possible to prove/disprove this until proper
clinical research has been funded and conducted.
|The vaccine was not properly tested.
||In the context of the MMR/autism debate, and the alleged
link, this is factually true, and it is extraordinary
for the Department to claim otherwise. Even the Department
cannot re-write history.
|My child has already received one dose, so does not
need a second dose.
||This is not the issue in dispute.
|My son does not need protection against rubella, my
daughter does not need protection against mumps.
This is not the issue in dispute.
|The Department of Health’s leaflet ends, "All
of the above are wrong".
||In the view of the parents, of the "Top 10 Myths",
four are irrelevant to the debate about an MMR/autism
link, one statement about a "Myth" is factually
incorrect, and the remainder can readily be disputed because
the research has not been completed, or in some cases
even commissioned, to decide the issue either way.
It is not in dispute that vaccines have saved millions of
lives. The MMR/autism parents are not anti-vaccination in
principle. These parents all took children to be vaccinated.
We all recognise the need to protect children from diseases.
But saving lives from diseases doesn’t justify ruining
significant numbers of lives from unrecognised and unmonitored
It is also felt by many parents that the mantra "the
benefits of vaccination outweigh the risks" has become
increasingly skewed by
(a) occasionally overstating the dangers of diseases, citing
experience of diseases from poor and underdeveloped countries,
or UK experiences from half a century ago, or pointing to
recent deaths (e.g. Ireland) where other factors played a
major part, or
(b) grossly underplaying or dismissing outright any risks
from vaccination. This latter has been aided by the extremely
poor monitoring of adverse outcomes, and by the authorities
strenuously refusing to accept that an adverse outcome was
the result of a vaccine.
All affected parents are in the privileged position of having
watched their child degenerate. It is a powerful first-hand
experience. Comparing notes results in finding that other
parents have undergone extremely similar experiences. Unfortunately,
such experiences are not part of a scientifically-controlled
study, so are routinely dismissed by the Department of Health
Usually there appears to be a very gradual degeneration over
many weeks and months, not an acute event, more akin to (eg)
the onset of cancer than the rare acute reactions to vaccines
seen in the past.
But all the attention of the past upon possible adverse reactions
to vaccines has focussed upon acute near-immediate events.
The onset of gut/bowel problems and hyperactivity have accompanied
the onset of autism. Some link between them is therefore likely,
even without detailed research.
An anecdote is an anecdote. A consistent pattern of anecdotes
is much more powerful. What we have is a consistent detailed
pattern of reports from parents. The importance of this pattern
has been ignored by the Department of Health.
Quite apart from the immense social costs of autism, there
are the huge financial costs. Autism effects every UK and
US taxpayer. In the UK, the costs comprise:
Health costs - specialist hospital visits, GP visits, prescriptions,
exclusion diet costs
Education costs - special schools, extra teachers, extra teaching
assistants, extra training
Transport costs - taxis plus drivers and escorts, plus local
authority management costs, plus environmental/congestion
costs of extra traffic
Social Services costs - respite care costs, transport, management,
Social Security costs - carers allowances, disability living
Inland Revenue costs - loss of earnings of parent, loss of
revenues from child when he/she reaches earning age
Wider economic costs - loss of gross domestic product to the
It would be interesting to know if the UK Treasury had a view
on these costs, and whether sufficient resources were being
devoted to investigating acquired autism and other forms of
autism, as they represent a significant loss to the wider
national economy. Is autism too important to be left to the
Department of Health?
In June 2000 a study for the Mental Health Foundation found
the annual costs of autistic disorder in the UK were at least
individual lifetime costs per child affected could run to
£2.94 million each.
The full costs, taking into account wider economic costs,
are probably considerably higher still.
There has been a consistent argument on the part of the authorities,
and those seeking to defend MMR, that the apparent rise in
autism may be largely a matter of better recognition. This
has received some backing from autism researchers. But where
hard UK or US data is available, increases are far too steep,
and in far too short a timescale, to be credibly ascribed
to better recognition alone..
For this to be "better recognition" or "improved
diagnosis", this would have required these children to
have been missed, simultaneously, by their parents, their
relatives, their doctors and their teachers in the past This
is simply not credible. For example, the increase in autism
1992-99 in Wakefield, West Yorkshire, local education authority
was from 5 cases to 111 cases. If increased autism is down
to better recognition, it would mean that, back in 1992, there
really were 111 cases, but only 5 were recognised, and the
remaining 106 were missed, and by all the parties - parents,
doctors, health visitors, teachers - concerned. This is completely
Undoubtedly there has been some degree of better recognition
and reclassification, following introduction of ICD-10 (international
classification of diseases/disorders) criteria in 1992, and
DSM-IV (diagnostic statistics manual) criteria in 1995. But
this will account for only a minority of the growth.
The UK DoH has failed to monitor autism, and is still failing
to (despite a specific 1997 recommendation of the House of
Commons Health Committee to do so). Is it now afraid of what
it might find? If it does decide to monitor autism, will it
find that numbers are high and then claim it has always been
UK Health Boards/Authorities are also failing to monitor autism
locally. Health Boards/Authorities have little data and no
consistent approach. At the health authority level, official
figures vary wildly, by factor of 300-fold, i.e. 300-times
(not 300%). The data is an extraordinary mess.
In the year 2000, only 1 in 6 UK Boards/Authorities had any
credible figures at all. Most used estimates from textbooks.
The Scottish schools census now includes autism. The census
commenced in 1998. The 1999 census showed 18% increase over
the 1998 census. The 2000 census showed a 31% increase over
the 1999 census. The 2001 census will report during mid-2002.
There are other indications of the level of increases: Kaye
et al paper (see later) found a sevenfold increase 1988-99
in UK. An unpublished 1999 paper by Dr. Fiona Scott, Autism
Research Unit, Cambridge, indicated autism at eleven times
the expected level (1 in 174) - see later.
The 2001 Medical Research Council review found autism to be
at 1 in 166, many times higher than hitherto thought. Sixteen
studies published between 1966 and 1991 found rates of between
1 in 3030 and 1 in 625. A rate of 1 in 166 is nearly four
times higher than 1 in 625, itself the highest of these sixteen,
and from a relatively-recent study in 1983.
Urging that the apparent increase is down to better recognition
may therefore be little more than a counsel of complacency.
Autism was a very rare condition, but is now almost regarded
as commonplace. Very many cases are now of late-onset autism,
whereas almost all used to be cases from birth. We have to
ask why this is.
Some UK research noted the sharp increases in autism in the
1990s. A paper by Powell et al, Department of Public Health
and Epidemiology, University of Birmingham, UK, Changes in
the Incidence of Childhood Autism and Other Autistic Spectrum
Disorders in Pre-School Children from Two Areas of the West
Midlands, UK, was published in Developments in Medicine and
Child Neurology, September 2000. This looked at the incidence
of childhood autism and ASD in pre-school children between
1991 and 1996.
The study found that there were year-on-year increases in
classical autism during this period of 18%, but for "other
ASDs" the annual increase was no less than 55%. But the
study then concluded that this was due to clinicians being
increasingly able or willing to make a diagnosis. The possibility
of an underlying genuine increase, and any follow-on question
as to causes, does not appear to have occurred to the study
But parents of children believe to have been damaged by MMR
strongly believe that part of the increase is down to a new
phenomena, autistic enterocolitis.
It is not the autism of the past. Such a severe acquired regressive
syndrome after a normal early childhood would have been noticed
in the past by parents, and recognised medically, and also
reflected in much higher historic rates of prevalence/incidence.
In the parents’ view, there is clear evidence of recent
examples - an East Surrey 1/69 rate amongst three year old
boys, 1/139 rate amongst three year old boys+girls combined
(source: personal communication of 10/6/99 from Caroline Clark,
Commissioning Manager, Learning Disability Services, East
Surrey Health Authority). The letter from East Surrey stated:
"In the remaining half of the District, it is estimated
that there are at least 50 children on the autistic spectrum
under the age of five. A special needs audit has been undertaken
of children aged three by the community paediatrician. This
is the age where the paediatrician expects to identify children
at the more severe end of the autistic spectrum. Thirty-six
children have been identified during the last two years as
presenting with autism, of which twenty-nine were between
the ages of two and three, with seven children slightly older.
The general population is around 2,500 children (born) per
year in this part of the District. The prevalence of autism
indicated by the audit is 0.72% (1 in 139) but with 1.44%
(1 in 69) for young boys."
Bromley Autistic Trust figures show a 1990-94 increase of
280% over 1980-84 figures (source: personal communication
of 16/9/99 from Miss C. M. Povey, Services Director, Bromley
Wakefield LEA autism pupils up from 5 to 111 in seven years
(source: survey by David Brown, a specially-seconded headmaster
from the Park School, Wakefield, on behalf of Wakefield Local
Education Authority, 1999)
Telford health data up from 4 new cases per year in 1990 to
17 per year 1998 and again 1999 (source: personal communication
of 20/11/00 by Dr F. R. J. Hinde, Consultant Paediatrician,
Princess Royal Hospital, Telford)
As noted, Scottish schools census up 18% in one year (1999
vs. 1998), and then a further 31% in the next year (2000 vs.
1999); (source: Scottish Annual School Censuses, available
from Scottish Education Office, tel 0131 556 8400)
On 18/2/01, the UK Sunday Telegraph reported on research undertaken
by Dr. Fiona Scott at the Autism Research Centre at the UK
University of Cambridge. The research, Prevalence of Autism
Spectrum Conditions in Children Aged 5-11 Years in Cambridgeshire
UK, by Scott, Baron-Cohen et al, which is due to be published
shortly, was undertaken across schools in Cambridgeshire.
It found that:
One in 175 (58/10,000) children was autistic, whereas previous
studies had pointed to a rate of 1 in 2000 (5/10,000)
Extrapolated across the UK, that would imply 30,000 primary
school (age 5-11) children with autism
Linking these rates to estimated costs of education and care
for sufferers would give a figure of as high as £5 billion
per year, year after year. The Cambridge autism figures were
described as "if anything an under-estimate". They
included only children with a definite clinical diagnosis.
Any child who had only been "statemented" (= educational
needs-assessed) as autistic, but not yet clinically diagnosed,
was not counted
One in eight children with special educational needs was suffering
from some form of autistic spectrum disorder. The increase
of actual numbers over previously-assumed numbers would have
enormous cost implications for central and local Government
A year-2000 report for the UK Mental Health Foundation by
Professor Martin Knapp for the UK Institute of Psychiatry
used the earlier "textbook" rate of autism of 5/10,000
to put the total UK economic cost of autism at £1bn.
The Knapp report estimated the lifetime cost of a severely-affected
child at £3m, for a high-functioning autism child at
£0.8m, and for an Asperger’s syndrome child at
£0.5m. The revised £5bn per year estimate is based
upon these costs.
An unpublished study by the UK University of Sunderland found
a tenfold increase in diagnosis of autism, during the years
The NAS issued a factsheet in early 1997 which gave the following
People with Kanner syndrome (IQ less than 70) 5/10,000, or
1 in 2,000
Other spectrum disorders (IQ less than 70) 15/10,000, or 1
Asperger’s (IQ 70 or above) 36/10,000, or 1 in 278
Other spectrum disorders (IQ 70 or above) 35/10,000, or 1
Combined total of above four groups 91/10,000, or 1 in 110
The above implies a very high level of autism in the UK, and
the previously-described studies seem to bear this out.
The NAS reach its 91 in 10,000 or 1 in 110 rate by taking
the Wing & Gould study (Camberwell, London) of 1979, which
looked at children with an IQ of under 70 and found a rate
of 20 per 10,000, and adding this to the study by Ehlers &
Gillberg (Sweden) of 1993 which looked at autistic children
with an IQ of over 70 and found a rate of 71 per 10,000 (1
The 91/10,000 rate is thus "merged data", collected
in two different countries and some years apart, and thus
needs to be treated with caution, particularly if rates have
since been rising further. The Wing & Gould study is now
over two decades out of date, and also pre-dates MMR introduction
into the UK.
The purposes of this report included:
To establish numbers of children with autistic spectrum disorders
To learn whether UK local education authorities believed there
had been a recent increase in the last five years
To ascertain whether LEAs routinely collected data
The findings included the following:
100 out of 115 LEAs reported an increase in autism in the
past five years. Some reported small increases, others reported
far higher increases, in one case by 77%.
The study compared the expected prevalence rate of all autistic
spectrum disorders in each LEA (91 in 10,000 or 1 in 110)
with the actual recorded number of children with ASD and a
Statement of Educational Needs (21 in 10,000 or 1 in 476).
If the estimated numbers are correct, then the implication
is that 75% of children with autism do not become included
in the Statement data, because they have no Statement.
Only 44 out of the 100 LEAs reporting an increase had actual
data. Some of these reported dramatic increases, up to 400%
in four years.
These are some recent, and sometimes self-contradicting, statements:
"There is no good evidence that the frequency of autism
has increased since the introduction of MMR" - Tessa
Jowell, then Minister for Public Health, October 1997 (personal
communication to David Thrower)
"The true incidence of autism is uncertain" - Sir
Kenneth Calman, then Chief Medical Officer, March 1998
The apparent rise in autism in the UK began more than ten
years before the introduction of MMR" - Tessa Jowell,
in June 1998
"Rates of autism are rising, but not because of MMR"
(Committee on Safety of Medicines, June 1999)
"There is no robust data on the prevalence of autism
before and after MMR’s introduction" - Brent Taylor,
in a June 1999 study heavily quoted by the Department of Health
"Numbers of cases of autism are rising, but the reason
for this is unclear" - John Hutton, Minister for Public
Health, December 2000
The UK DoH is fond of saying how MMR is safely used in 32
countries, including the USA, as though its use elsewhere
is proof in itself that it is safe. But the USA, at least,
has clear evidence of an autism epidemic. Other countries
may also be becoming aware of increases, for example Finland,
where a 400% increase in cases has been alleged since was
The US has IDEA (Individuals with Disabilities Education Act).
This picks up numbers of schoolchildren with developmental
problems. Autistic pupils are up from 12,222 to 65,396 between
1992-1993 and 1999-2000 (Source: US IDEA State data). So for
every 2 cases there were in 1993, by 2000 there were nearly
11. Numbers will have risen even further since.
To the above total also has to be added a further 15,581 cases
of autism amongst children aged 3-5 years, as at year 2000.
There have been huge increases in some States between 1992-1993
and 1999-2000 - up 885% in Alabama, 529% in Connecticut, 435%
in Florida, 513% in Idaho, 636% in Kansas, 561% in Minnesota,
all in just seven years (Source: US State data, Individuals
with Disabilities Education Act)
It is also interesting that individual towns such as Round
Rock, Texas, are reported to be up from 6 cases to 115 cases
in eight years - very much like Wakefield Local Education
Authority in the UK (up from 5 to 111 in seven years). On
the face of it, this suggests that UK increases may very closely
match those in the USA.
The latest California increases (the State with the best database)
showed autism up 19% in 1999 and up again nearly 16% in 2000.
It has been alleged that Brick Township (New Jersey) has manifested
an "autism cluster". Some 40 of Brick Township’s
6,000 3-10 year olds have autistic spectrum disorder. It has
made Brick Township the "autism capital of the USA"
(but note, East Surrey rates in the UK are higher still).
In Brick Township, Federal investigators collected data on
surface and ground water, sites of industrial spillages and
waste dumping, and also ensured that there had been correct
diagnosis of the actual children. They have found nothing
untoward. Their findings were reported in April 2000.
The latest statistics produced by the Department of Education
in the United States, for numbers of children aged 6-21 served
by IDEA (Individuals With Disabilities Discrimination Act)
who have autism are as follows:.
The following is taken from the statistics produced by the
Department of Education in the United States, for numbers
of children aged 6-21 served by IDEA (Individuals With Disabilities
Discrimination Act) who have autism. It compares the increase
over the eight years between 1992-93 and 2000-01:
|District of Columbia
|| (almost infinite)
| North Carolina
| South Dakota
||overall increase 644
Individuals With Disabilities Education Act data, US Department
of Education. Note: Where increases are from a very low base
figure, these have been expressed as "almost infinite".)
For every two cases there were in 1993, there are now thirteen.
And the latest 2000-2001 figures represent a single-year increase
of 20% over 1999-2000
The current estimate for the year-end of 2002 is 94,000-95,000.
It seems obvious that the US has an autism epidemic. The UK
is a similar health environment to the US, so it also seems
reasonable to conclude that the UK probably has an autism
epidemic, too, but just hasn’t yet realised it.
Dr Bernard Rimland of the US Autism Research Institute, San
Diego: "Some supposed experts will tell you that the
(US) increase reflects only greater awareness. That is nonsense.
Any paediatrician, teacher or school official with 20 years
experience will confirm there is a real increase, and the
numbers are huge and growing".
California has probably the most useful autism data in the
world, going back to 1970. Trends monitored there have a potential
The rise in autism was first highlighted by a report Changes
in the Population of Persons With Autism and Pervasive Developmental
Disorders in California’s Developmental Services System,
1987 through 1998 - A Report to the Legislature, tabled on
March 1st 1998 by the Department of Developmental Services,
Sacramento, California Health and Human Services Agency.
The latest Department of Developmental Services data, released
at the start of 2002, shows that a record number of professionally-diagnosed
DSM-IV criteria autism cases, 2,725 cases, entered the State
system during 2001.
This year-2001 number represents a 20% increase over the year
2000, itself a record.
In 2001, there were more cases of level-one autism in California
than in 1994, 1995 and 1996 combined.
Historically, autism made up 3% of childhood disability in
the State Developmental Services system. It now comprises
35% of the total.
Two out of three persons with autism in California’s
child-developmental system are now young children between
the ages of 3 and 13. Eight out of ten persons with autism
have been born since 1980 (1980 was the year that California
mandated the full complement of childhood vaccines as a condition
of school entry. MMR was also introduced in California 1979-80).
California now has 16,802 persons with level-one autism in
its Developmental Services system.
The total intake for the three years 1999-2001 was 6,596.
This compares with a total intake for the twenty-five years
1970-1995 of 6,527 cases.
This does not include children with persistent developmental
disorder, non-specific (NOS) developmental delays, Asperger’s
or and other autistic spectrum disorder - it is therefore
the tightest definition of the severe-case numbers.
Data on autism in New Jersey, recorded by the IDEA system
for individuals with disabilities who require special education,
suggest that there is a vast preponderance of cases amongst
children/young people ages 6-21 amongst the youngest ages.
The following figures relate to the position as at 1st January
age 6 7 8 9 10 11 12 13
nos 514 505 465 439 360 257 208 165
age 14 15 16 17 18 19 20 21
nos 145 124 81 73 58 63 30 14
The total number of cases is 3,501. This equates to an average
of 219 for each age-year. For ages 11 and under, the number
exceeds this average, and for ages 12 and over, it is less
than this average.
The youngest three years average out at 495 cases. The oldest
three years average out at 36 cases. The average of the youngest
years is about 14 times that of the oldest three years.
This section deals with the numerous recent official studies
and reviews, many in the UK but some in the US or elsewhere,
that "prove" there is no connection between autism
As will be seen, all when scrutinised critically are actually
either irrelevant, inconclusive, or are seriously methodologically
The UK Government’s advice on MMR and autism comes from
the DoH, the Medicines Control Agency (MCA), the Committee
on Safety of Medicines (CSM) and the Joint Committee on Vaccination
and Immunisation (JCVI). These bodies are closely intertwined,
and have based their position on a barely more than a handful
of studies. Further advice has come from the Medical Research
Much of the focus has been upon the need maintain public confidence
in MMR to prevent communicable diseases, rather than the need
to investigate specific cases of alleged damage.
The studies are also of random groups of children, but not
of the actual children reported by parents as damaged by MMR.
Finally, the Department of Health has implied in the past
that the evidence for a link between MMR and regressive autism
has come from only one team of researchers, which is not factually
correct. However, the very same criticism can be levelled
at the "anti-link" camp. A significant proportion
of the studies below only comes from a very small number of
sources, some very close to the Department of Health itself.
This paper, by Stokes, Weibel, Villarejos, Jorge, Arguedas,
Buynak and Hilleman, has assumed more importance recently
(see later Wakefield/Watson/Shattock debate section).
The paper stated that triple vaccines were desirable to simplify
administration, reduce costs and minimise visits (my emphasis).
There was no mention of greater effectiveness, or inherent
drawbacks with single vaccines.
There were three trials, firstly of 30 children in Philadelphia,
then of 214 children in Philadelphia, then of 440 children
in rural Costa Rica and San Salvador, total 684 but (note)
of very different economic and geographical backgrounds.
The mean ages of children in the three trials was 1.1, 1.5
and 3.0 years. Note that the present age of receiving MMR
is about 14 months, and therefore the vast majority of the
trial children were significantly older than today’s
UK MMR recipients. Some 64% were also not from Western social/health
The 30 children’s parents were given report cards for
recording temperatures for 28 days, and queried at six to
nine weeks. For the 214 child-cohort and the 440 child-cohort
trials, follow-up was 28 days. The parents were instructed
to notify any significant illnesses during the 28-day period,
and were queried at the second bleeding, six to nine weeks
after vaccination - but the implication is that this query
may have covered the 28-day interval, not longer.
The study noted that "the fifth to twelfth day after
vaccination is the critical time period for occurrence of
the expected low incidence of febrile reaction", also
that the significance of the difference between vaccinees
and controls in terms of miscellaneous subsequent complaints
(gastroenteritis included) was "doubtful" (though
it was actually very marked in the study tables, up to 18/228
of vaccinees with gastroenteritis, compared with at most 3/106
At no point in the study was autism mentioned as a risk-factor
or an actual outcome. Clearly, the possibility was not even
considered. The study noted the lack of arthritis and arthralgia.
Overall verdict: this study is not relevant to disproving
an MMR/autism link
This study sought to check levels of adverse reactions following
MMR. MMR was introduced into Finland in 1982, being administered
at 14-18 months and at 6 years, using Merck Sharp Dohme Viravac.
The study was a double-blind crossover study involving 581
twins. The vaccines were administered blind, but one twin
of each pair first received active MMR, then three weeks later,
received a placebo. The other twin was given the placebo first,
then three weeks later received MMR.
Each twin was given a colour coded questionnaire to be completed
daily by parents, for 21 days after the injections.
In theory, this should have provided a foolproof test of how
reactive MMR was. However, the study completely founders on:
the issue of the potential time-delay between receipt of MMR
and any possible gradual degeneration into autism. If such
a delay could exceed 21 days, then the study would have missed
it as an adverse reaction
Secondly, the linking of autism/developmental delays with
MMR, or indeed any other vaccine. Parents in 1982, or indeed
until about mid-1997, were not linking MMR with autism. It
is extremely unlikely that regressive autism would have been
connected, in the minds of either parents or the study authors,
with MMR back in 1982. Virtually no literature or press reports
had appeared on the issue.
As with the original safety trials of MMR (see later papers),
this study was not designed to verify whether rare and complex
adverse events might follow months or years after MMR.
The study only looked at one brand of MMR. As subsequently
transpired, some brands of MMR used in the UK and elsewhere
had a less satisfactory safety record than others, and (in
the UK) were withdrawn at very short notice in 1992. A study
with Viravac cannot be used to give safety clearance to other
brands if the brands are found to have been variable.
A further criticism is that the study is still quite small
in relation to rare events. It involved 581 twins. All other
things being equal, if a rare adverse outcome occurred at
a rate of 1 in 2 x 582, or less frequently, this study would
not have found it.
The authors did actually acknowledge this, stating:
"The study was designed to explore relatively common
symptoms and signs occurring after the vaccination" (they
mean, "within 21 days of"), and
"Rare reactions due to the MMR vaccine cannot be studied
with this small sample".
It is therefore suggested that this study, regarded as the
"gold standard" by the exponents of MMR, offers
no evidence for or against an MMR/autism link; it is clearly
irrelevant. Overall verdict: this study is not relevant to
disproving an MMR/autism link
This paper was to report the incidence and severity of clinical
reactions before the start of the UK national MMR programme.
MMR was offered to 10,000 children in three districts in the
UK, with a post-vaccination follow-up of every child.
Two types of MMR were introduced, Immravax in Somerset, England,
and Pluserix in Fife, Scotland, and North Hertfordshire, near
London. Both vaccines contained Schwarz measles and Urabe
9 mumps vaccine, and both later had to be withdrawn in 1992
for safety reasons, in connection with risks of aseptic meningitis.
These risks were not detected by this study.
The study found that:
Of the 7,247 children aged 1-2 years, 38% had either no symptoms
or symptoms for only one day
18 had convulsions. Fifteen were admitted to hospital.
Of the children aged 4-5 years, 61% had either no symptoms
or symptoms for one day. There were no convulsions and no
Follow up was for 21 days. However, 114 children were followed
up through diary records for a further 21 days, total 42 days.
Comparison of symptoms of children after MMR was made against
symptoms of children after measles vaccination - not unvaccinated
The study concluded that symptoms reported after MMR appeared
to be similar in nature, frequency, time of onset, and duration,
to those recorded in earlier studies after monovalent measles
Comment: as with the original safety trials of MMR, follow-up
was extremely short and only immediate/near-immediate reactions
noted. The study did not look at autism, but effectively cleared
the way for MMR’s general introduction into the UK.
It is noteworthy that the study was co-authored by Dr. Elizabeth
Miller, who subsequently authored or co-authored several of
the studies that have been used as "proof" that
there is no MMR/autism link. It is also noteworthy that, as
noted, this study missed the aseptic meningitis problem of
MMR, and that the brands of MMR with Urabe strain mumps virus
subsequently had to be withdrawn, in 1992, at extremely short
Overall verdict: this study fails to disprove an MMR/autism
The paper reported a study in Sweden by Gillberg et al, 1991.
It has been partially updated since (see below).
Gillberg looked at tiny sample of autistic children (55 of
typical autism, just 19 of atypical autism), in Goteburg and
Bohuslan. The study, actually a mish-mash of three studies
with differing criteria, does not mention vaccination, does
not state the coverage of MMR, does not include data on uptake
or demographic factors, and is therefore irrelevant to the
It had tracked down cases of autism unscientifically, by word
of mouth, doctors etc., then allocated them by d.o.b. to "pre-MMR"
and "post-MMR" eras
The study’s case-selection being a few cases out either
way would neutralise or completely reverse the findings of
The paper does acknowledge that the rate of autism has increased
but "explains" this through changes in population
structure and "better diagnosis".
Overall verdict: this study offers little evidence that MMR
does not cause autism, particularly as it is so small.
This further paper by Gillberg was published following
the appearance of the Wakefield et al "Early Report"
paper in The Lancet in early 1998.
Gillberg and Heijbel stated that they had re-analysed the
data from their population study of autism performed in the
late 1980s and published in 1991 (as above). The children
in that study (n = 55) had been born in the ten-year period
1975-84. The authors claimed that as MMR was introduced in
Sweden for 18-month-old children in 1982, with coverage increasing
rapidly to 90%. The authors then argued that if there was
an MMR/autism link, then children born from July 1980 onwards
(i.e. The post-MMR generation) would be expected to be at
increased risk. The 55 children were therefore divided into
34 (62%) pre-MMR and 21 (38%) post-MMR.
The authors then argued that had there been a strong effect
of MMR, they could have expected more than 45% of the 55 cases
of autistic children to have fallen into the post-MMR group.
As this was not the case, then their study did not support
the hypothesis of an association between MMR and autism
The authors also again claimed that in their parallel study
of 19 atypical autism cases, there would have been a similar
effect, and therefore that again there was no support for
Overall verdict: as with the original study, these numbers
were so small as to render this study, and its conclusions,
as virtually without value in the context of proving/disproving
an MMR/autism link. Statistical/epidemiological studies based
upon cohorts numbering 55 and 19 cases are far too small.
It is extraordinary that the UK Department of Health was using
this study in the late 1990s to "disprove" the suggested
This letter set out two studies that attempted to prove that
there was no connection between inflammatory bowel disease/Crohn’s
disease and autism. The first study looked at UK clinical
data collected by the Child & Adolescent Psychiatric Services
of the Maudslay Hospital, London.
For ASD, three diagnostic groups were examined, autism, atypical
autism including disintegrative disorder, and pervasive developmental
Medical disorders were coded for a 25-year period, including
Crohn’s and ulcerative colitis, for 8889 patients.
Of the 8889 patients, 987 were born in 1987 or later, and
were therefore most likely to have been exposed to MMR. Of
these, 201 had ASD.
Of the 8889 children, only two had Crohn’s, and both
were non-autistic. None had ulcerative colitis.
For the second study, a similar approach was undertaken. Fombonne
surveyed medical, behavioural and intellectual disabilities
amongst 6100 French children.
He found 174 cases with autism.
One child of the 6100 had Crohn’s, and one had ulcerative
colitis. Neither were autistic
The conclusion that Fombonne drew was that these data provide
no support for the hypothesis of an association between IBD
Overall verdict: neither of these studies offer any evidence
to disprove an MMR/autism link.
This study looked at the medical records of some of the children
who are now taking High Court action. Their details were provided
by their lawyers.
The study admitted:
Information on the children was extremely variable in quality
It was "difficult" to draw conclusions about any
causal association (verbatim quote: "the information
evaluated has important intrinsic limitations as regards assessing
whether the vaccines are or are not causally associated with
the adverse effects")
It was not feasible to review the less common adverse side
The study was effectively run as knockout competition. Each
case had to pass four hurdles (all four) to be counted as
being caused by MMR. The four hurdles were: (1) have either
the diagnosis or clinically relevant signs/symptoms been confirmed
medically? (2) was the onset of the possible adverse effect
within six weeks of immunisation with MMR? (3) was there history
prior to immunisation relevant to the possible adverse effect?
(4) was there evidence of other causes for the possible adverse
Six weeks after immunisation was chosen as a cut-off point
for a close temporal association because (quote) "this
is the maximum period in which viral replication can be detected
after immunisation". But this probably missed many cases,
and is arbitrary. The Spitzer, Aitken et al study (see later)
renders this six-week limit as irrelevant.
At every stage, the study looked for other "causes"
to explain-away the cases, and took every opportunity to ascribe
cases to these "causes". In most cases, it was assumed
at every stage without scientific justification that autism
was "caused" by other factor rather than MMR. But
it is not known what causes autism. Therefore there is a gross
study bias, and the study rests upon unscientific assumptions.
The other assumed "causes" were the child’s
previous medical history, comprising having a parent/sibling
with speech or behavioural problems, an obstetric history
of pregnancy complications (these, alone, were not considered
as "causes"), signs/symptoms of encephalopathy,
a head circumferences larger than the 97th percentile, or
history of unspecified viral illnesses, bronchiolitis, rubella,
measles, or a minor head injury.
The study eventually only looked at 92 cases of autism in
detail (plus 15 Crohn’s), and was left with a residue
of 8 autism cases and four of the Crohn’s it could not
"explain" away. These were then just set aside,
What the study did was to introduce so many extraneous considerations,
and accord these such an importance, that hardly any case
with sufficiently-clear documentation remained to survive
the appraisal process. This eliminated almost all cases. The
study then appears to have then simply set aside the residue.
The study text commented that (quote) "it was impossible
to prove or refute the suggested associations between MMR
vaccine and autism or inflammatory bowel disease because of
the nature of the information.". This would seem to inevitably
render the study as inconclusive. But the study’s conclusions
did not reflect this sentence.
The wording of the final conclusion left a small exit-route
for any possible future U-turn: ""On the basis of
all the available evidence, the demonstrated benefits of MMR
or MR vaccines far outweigh any possible risks" (my emphasis).
The DoH’s press release 0342 of 1999 spun the study’s
conclusions further - "Two New Independent Studies Have
Not Found A Link Between MMR Vaccination And Autism"
Note: this is the only study to date to have both looked at
the actual children reported to have been damaged and to have
"cleared" MMR. But as the above criticisms show,
the study was actually self-admittedly inconclusive. It also
failed to medically examine the actual children.
Overall verdict: this study does not disprove an MMR/autism
The study, designed by Dr Elizabeth Miller of the Public Health
Laboratory Service, was wholly inconclusive, but has been
widely presented as conclusive proof of the absence of any
link between MMR and autism.
It only looked at 498 cases, far too small a sample for a
robust statistical (case-series analysis) test. The study
attempted to track-down children through special schools and
local authority special needs registers - a method that is
open to question, as it probably misses many cases. The study
describes itself as "a large regional sample", but
it was actually very small.
Taylor, Miller found a steep increase in autism, ("There
was a steady increase in cases by year of birth"), but
did not explain it.
Also, the study looked for a time-clustering of parental concern
six months after MMR, found it, but then dismissed it unconvincingly
by saying it was "related to the difficulty of defining
precisely the onset of symptoms". But this method, of
precisely identifying a date, was meant to be the very basis
of their study.
Also, the study did not include in its post-MMR numbers those
children born 1986-87 who later received it, nor those 2/3/4
year olds who had MMR at this older age.
It also missed children who had single vaccines, then MMR
later. It not only misses these from "post-MMR"
numbers, but added them to its pre-MMR numbers. The whole
study is thereby compromised. The authors have since sought
to clarify this in correspondence in The Lancet, but unconvincingly.
Autism is sometimes not diagnosed for years after. It is very
difficult to pin down an actual "date" of diagnosis,
and many children don’t receive any formal diagnosis
anyway (contact National Autistic Society, which did a study
on this, tel 0207 833 2299). The Taylor Miller study doesn’t
The study seems to have been designed to clear MMR, not to
test whether there is a link with autism. The study struggles,
and fails, to disprove a link.
Also, the study is described by the UK DoH as "independent".
But Taylor was co-author of a 1988 paper clearing the safety
of triple vaccines, Miller was described in Daily Express
press reports of 1/01 as "a colleague of Dr David Salisbury"
(head of the DoH Immunisation & Communicable Diseases
Branch, which runs the MMR programme), and the study was funded
by the UK Medicines Control Agency, a satellite of the DoH.
The authors have been repeatedly challenged by other researchers
to release their raw data but have refused. Yvette Cooper,
the UK Minister for Public Health, has backed up their refusal.
Overall verdict: despite its claims, this study cannot be
taken as proof of there being no MMR/autism link, due to its
apparent serious methodological flaws.
In their submission to the US House of Representatives Committee
on Government Reform Hearing, which was investigating increases
in autism and possible links with vaccination, Miller and
"Our conclusion, based on the findings of our study,
is that there is no evidence of a causal association between
MMR and autism".
"The case series method has a proven track record with
respect to identifying and measuring a risk of adverse events
after various vaccines".
"In our study, we showed that the increase in the prevalence
of diagnosed autism in recent birth cohorts occurred during
a time when the coverage of MMR vaccine in the same cohorts
has been constant. The rise cannot therefore be related to
the use of MMR vaccine."
"There is no credible epidemiological evidence to support
the view that measles vaccination is a risk factor for Crohn’s
disease or any other inflammatory bowel disorder".
However, as explained in the section covering the original
paper by Miller, Taylor and Farrington, there are major questions
over the methodology of this paper; these, of course, can
also be applied to Miller and Farrington’s paper to
the Government Reform Committee.
This Finnish study, usually referred to as the Peltola study,
concluded that serious events rarely were related to MMR.
The study was initiated in 1982, when MMR was introduced.
A nationwide surveillance system was set up to detect serious
adverse events, reviewing patients’ clinical records
and where taken, serum samples. However, the study relied
on passive surveillance - a fatal flaw - and only followed
up acute adverse events - a further fatal flaw.
According to the report,
173 potentially serious adverse reactions were claimed to
have been caused by MMR, out of almost 3 million doses.
There were 77 neurologic reactions, 77 allergic reactions,
22 miscellaneous reactions and one death.
Some 45% of these reactions were dismissed by the study as
probably caused or contributed by other factors.
Peltola admitted on BBC Radio 4 on 13/1/01 that the Finnish
study was not designed to look at either autism or inflammatory
bowel disease. He confirmed that the study was not specifically
designed to look for autism, as no-one had ever raised this
issue at the time.
The Peltola study simply identified the 173 children (out
of 1.8m persons, including troops), who had acute reactions
to MMR, then followed only these children up. The study followed
up the wrong children. No-one has ever suggested that autism
follows an acute reaction.
There would almost certainly have been potential autism cases
amongst the remainder of the 1.8m, but these were missed,
because they were excluded from the study, as it had a 3-week
cut-off for reporting reactions. After that point, the remaining
(theoretically, 1,799,827) children/other persons were ignored.
Peltola relied on referrals from health workers out in the
field, who would never have connected degeneration into autism,
several months/years after MMR, as being a potential adverse
reaction to a vaccine. The alleged syndrome was not known
of by scientists, let alone by health-workers in the field,
at that time.
The UK DoH interpretation of this study, widely trumpeted
during 1/2001, is that Peltola "clears" MMR of a
link with autism/IBD. It is difficult to accept that this
"conclusion" has any degree of scientific justification.
It appears that the DoH’s "conclusions" have
been retrospectively bolted-onto an old and irrelevant study.
There are other awkward facts regarding the Peltola study:
The study was part-funded by Merck Sharp Dohme (MMR manufacturers).
The study barely refers to autism or IBD.
Reviews of the study (eg December 2000 Medscape) do not even
mention autism/IBD, which are obviously not seen by the reviewers
as a relevant aspect of this study.
Despite this, the Peltola study continues to be cited by the
UK medical establishment as conclusive proof that there is
no link between MMR and autism. As late as 12/2001, Dr. Simon
Fradd of the General Medical Council’s Doctor-Patient
Partnership quoted this study by Peltola on BBC Radio 4 as
conclusive proof of the absence of any link.
The UK DoH also said in a personal communication, referring
to all the various studies: "the follow-up time (three
weeks) was based on knowledge of the replication rates of
the vaccine viral components.....it is recognised that such
a study could not establish a causal relationship with extremely
rare events..... millions of children have received MMR in
other countries such as Finland and the USA; no serious long-term
complications have been identified...." (my emphasis).
Overall verdict: this study is wholly irrelevant to the issue
of whether MMR can cause autism.
This paper attempted to prove that there was no link between
MMR and autism because, although autism increased when MMR
was introduced, it has carried on increasing since, even though
MMR’s coverage reached near-saturation almost immediately
after its introduction into the UK in late 1988.
The study looked at 305 children (254 boys) aged 12 or under
with autism diagnosed in the years 1988-99. It also looked
at 114 boys aged 2 to 5 years born in 1988-93. It used the
UK General Practice Research Database.
The study found that autism had increased sevenfold from 0.3
per 10,000 in 1988 to 2.1 per 10,000 in 1999 (note how low
this figure is compared with other studies)
In the 114 boys born 1988-93, it found autism had increased
fourfold, from 8 per 10,000 (1 in 1250) for boys born in 1988,
to 29 per 10,000 (1 in 345) for boys born in 1993, during
a period when MMR take-up was claimed to be constant at around
The study concluded that no correlation existed between MMR
and autism, and that the explanation for increased autism
However, the authors acknowledge that their methods were a
"second-best", because what they really wanted to
do was compare vaccinated and unvaccinated cohorts of children.
They said that this was impossible because only 3% of cases
and controls did not receive MMR. Given the very small numbers
of autism cases they in the event actually looked at, this
seems an unconvincing argument for abandoning their preferred
The authors then argue that if MMR was a major cause, then
the risk of autism should have stopped rising within a few
However, they also admit that the diagnosis of autism was
not confirmed from original records, but conclude that "differential
misclassification of the diagnosis in vaccinated and unvaccinated
children is unlikely to vary over the period of the study",
though no evidence is offered to back this claim.
They also acknowledge that time trend analysis is a "relatively
The study authors go on to speculate that the increase in
autism that they found "could be due to increased awareness
of the condition among parents and GPs, changing diagnostic
criteria or environmental factors", without subjecting
these "explanations" to any detailed scrutiny.
The authors also acknowledge the further limitation that they
have not yet obtained and evaluated full clinical record information
from GPs to describe more fully the characteristics of children
diagnosed with autism and to explore other possible explanations.
Yet they still dismiss MMR, despite this shortcoming.
It might be the case that the increase in autism that the
authors find, over the period 1988 to 1997 (note - not 1999
- the study figures actually fall away after 1997) could be
due to a hybrid explanation, with increases in the early years
due to MMR and then continuing further increases in the later
years due to better awareness. There is nothing in the study
to refute this criticism
It is also unclear how the issue of re-vaccination has been
dealt with. What of the seven million children vaccinated
or re-vaccinated in 1994 in the UK "Operation Catch-Up"
programme? Couldn’t the continuing rise in diagnosed
cases in 1995-97 be due to Operation Catch-Up? The study does
not mention it.
It is interesting that the Finland study team (Patja et al)
said "Causality between immunisation and a subsequent
untoward event cannot be estimated solely on the basis of
a temporal relation." Yet the Kaye et al study uses a
basically similar approach to "prove" there is no
link, comparing temporally-linked trends in MMR take-up and
There is also a question over the use of mercury-based preservative
(thimerosal) in vaccines. This was used in the late 1980s
and early 1990s, but has reported to have been largely phased-out
in the US, with a free exchange system being operated by the
manufacturers. No such exchange has operated in the UK, with
existing thimerosal-based stocks being used up on the children.
Autistic enterocolitis may involve thimerosal as part of the
If it did, and following a change in formulation, then this
might well explain continued rises in autism through the 1990s,
then a fall-away in increases at the end of the decade, as
was actually found by Kaye et al. Did the industry change
the preservative formulation as public concern grew? And has
this affected the statistics of autism?
Overall verdict: this study offers no convincing evidence
against an MMR/autism link.
At the end of January 2001, a paper, "Is There An Epidemic
of Autism?" was published by Dr. Eric Fombonne. The paper
sought to deny that autism had really increased, and criticised
the "poor research methodology" of Dr. Andrew Wakefield,
and said "There is no need to raise false alarms on putative
epidemics nor to practice poor science....."
Fombonne criticises the California increase on the basis of
in-migration, possible changes within the population make-up,
the change from DSM-III to DSM-IIIR in 1987, the introduction
of diagnostic categories for Asperger, Rett and childhood
disintegrative disorder in DSM-IV in 1994, the effects of
earlier diagnosis adding to the totals, and other factors.
His most useful conclusion is that "we simply lack good
data". He raises doubts about the apparent epidemic,
but is then unable to refute it either.
In an excellent FEAT (parents’ group) critique (8th
Feb 2001), Mark Blaxill goes carefully through Fombonne’s
previous work and argues that Fombonne has become inconsistent.
He points out key flaws in Fombonne’s previous work,
and criticises his criticisms of the California data and his
This paper, entitled "Time Trends in Autism and in MMR
Immunisation Coverage in California" is one of the least
conclusive and least robust of all the research of recent
years. It appeared in JAMA, March 7th 2001, but it is surprising
that it achieved such a high profile within the UK, so weak
was its hypothesis and so inconclusive its contents.
The paper attempted to determine if a correlation existed
in trends of MMR immunisation coverage and autism occurrence.
It did this by examining data from 21 regional centres covering
the whole of the State of California.
During the years examined, 1980-94, MMR take-up was about
72% prior to 1988 and about 82% after 1988. Autism increased
from about 200 in 1980 to about 1200 in 1994. The trend of
increasing autism continued after the introduction of MMR
and was claimed to be unaffected by the increase in take-up.
This hypothesis, of a correlation, could be criticised as
not being useful to the detection of any MMR/autism link.
Although immunisation coverage can be determined, with a specific
"date of immunisation", autistic spectrum disorder
ranges from the mild to the severe, its onset ranges from
the rapid to the gradual, and its diagnosis varies from a
timely and accurate diagnosis to no diagnosis whatever. This
apparently was not taken adequate account of by Dales et al.
The study did acknowledge some weaknesses itself:
"Diagnosis is not always straightforward". This
is an extreme understatement.
"California Department of Developmental Services’
report stresses that its patient caseload data cannot be used
as a true measure of changes over time in autism incidence
because other factors can affect trends in system case numbers"
"Observation of parallel trends over time.......generally
do not constitute strong evidence for a causal association
between the two events"
"As the system expanded and matured over time, the proportions
of California children enrolling and the distribution of ages
at enrolment likely (my emphasis) changed over time as a result".
Clearly, the authors do not know, one way or the other, not
do they attempt to quantify this to enable their reliance
on the data to be validated, or appropriate potential distortions
in the data eliminated.
"Also, the proportions of children enrolling in the system
who were born outside California may (again, my emphasis)
have changed over this time period". Again, they do not
know, have not attempted to quantify this factor, and cannot
correct for it.
"The data presented herein have some limitations. It
would have been useful to examine individual immunisation
and autism records on the same children; however, these could
not be linked". What the authors are saying here is,
they would like to have done a rigorous study, but they couldn’t
obtain the data.
"Further, the childhood immunisation coverage data used
in this study do not provide precise quantification of the
percentage of children who received the combined MMR vaccine
product vs. separate injections". This is an admission
that one element of the two elements that provide the statistical
comparison that is central to their hypothesis, is inaccurate.
They go on to say that historical data from elsewhere in the
US "strongly suggests" that the use of separate
vaccines was "rare" for the 1984-94 birth cohort.
How strong? How rare?
Despite this catalogue of drawbacks and "softness"
- or complete absence - of data, the authors then go on to
claim that they have been "unable to demonstrate a correlation
between secular trends in early childhood MMR immunisation
coverage and autism caseload". A dispassionate and objective
observer would find this wholly unsurprising.
The assumption that there would be a plateau in the increase
in MMR (to match a plateau in take-up of MMR) would only be
valid if the background susceptibility of the infant population
has remained constant. If successive generations of children
became increasingly susceptible to an adverse event such as
autism, caused by MMR, then this might well be reflected in
a continuing rise in autism. This obvious possibility is not
addressed. It does not have to be the case that the relationship
between MMR and autism is a simple linear one, without other
factors being involved.
Overall verdict: this study is not relevant to disproving
an MMR/autism link If the study does have a value, it is to
demonstrate that extremely weak studies are not only capable
of achieving publication - apparently without attracting peer-review
criticism - but also that they are then uncritically welcomed,
and publicised, by one side of the argument. This in itself
This paper appeared in the British Journal of General Practice,
March 2001. It attempted to test the hypothesis that a degeneration
into autism, with subsequent diagnosis, would be reflected
in increased consultations with the child’s general
This would appear to be an extremely weak hypothesis to test.
It may be difficult to place a definite date upon degeneration
Parents may not seek assistance from their GP immediately,
or even at all in some cases
Parents may seek advice from health visitors or other health
Parents may see a GP only once, to obtain a referral to a
Parents may see their GP for reasons unconnected with autism,
confusing the data in some cases
Parent may be extremely reluctant to see their GP, because
of the sometimes extreme practical difficulties of taking
an autistic child to a public surgery, with waits etc.
The study authors do not acknowledge any of these serious
potential methodological flaws, nor do they attempt to quantify
them in an attempt to validate the effectiveness of their
The authors looked at only 71 cases of autism, a small sample
by any standard for testing a statistical hypothesis, and
identified numbers of consultations from a primary health
care database. It found that there was no significant difference
between cases and controls for numbers of consultations in
either the six months before/after immunisation, or the two
months before/after immunisation.
The study also noted
that there was a significant fall-off in consultations in
the six months after immunisation, in both cases and controls.
However, it did not address the possibility that this might
have been for two entirely different reasons, with healthy
children not needing to be taken to their GP, and autistic
children not being seen by their GP for other reasons such
as those set out earlier. The study simply assumed that the
fall-off in the cases and the control group was for the same
reason, without evidence to underpin this assumption.
It acknowledged that it could be criticised because the study
authors "cannot confirm that our cases truly suffer from
The study, like almost all other studies that "prove"
no MMR/autism link, did not specifically address the cohort
of children alleged to have degenerated as a consequence of
MMR, and who are now proceeding through the legal processes
It acknowledged that "some diagnoses will have been missed"
It admitted that "it seems unlikely (my emphasis) that
these will be specifically those associated with MMR",
although it offers no evidence to support this assumption.
The study notes that ""the clear difference in consultations
in the six months before the diagnosis of autism" (between
cases and controls) "emphasises that consultations were
being recorded and that differences in consultation rates
between cases and controls were detectable". But the
study does not address the possibility that the higher frequency
of consultations by cases is linked to a potentially-associated
condition, such as otitis media (and consequent antibiotic
use), and that cases moved from more frequent consultations
than controls for such a condition, to more frequent consultations
than controls for a wholly different and more serious condition.
Overall verdict: this study is not relevant to disproving
an MMR/autism link. In short, there are so many caveats, acknowledged
and unacknowledged shortcomings and other methodological limitations
to this study that its conclusions are virtually valueless.
Again, it is illuminating that it has been so well received
by one side of the debate (the UK Department of Health).
This study was conducted in the US on the populations of four
health maintenance organisations as part of a vaccine safety
programme co-ordinated by the Centres for Disease Control
The study focussed on the following questions:
Was the age of first vaccination with MMR or other measles-containing
vaccine, or receipt of vaccination itself, associated with
an increased risk for Crohn’s disease or ulcerative
colitis later in life?
Was receipt of MMR or other MCV associated with the acute
onset of disease shortly following vaccination?
In each of the areas, trained staff reviewed medical records.
Cases were of individuals enrolled since birth (some as early
as 1958) to 1989. It was claimed that consistent criteria
were used for definite and probable diagnosis of Crohn’s
disease, ulcerative colitis or unspecified irritable bowel
disease. This involved diagnosis by a gastroenterologist,
"with signs and symptoms and a diagnostic test for IBD".
Five controls were selected for each case, matched by sex,
health organisation and year of birth. Dates of vaccination,
type of vaccine and date of diagnosis were also recorded.
There were 155 cases of IBD with 152 definite or probable
cases. Seven had no discernible onset, two were of "unspecified
disease" and one was vaccinated when older than 10 years.
This left 142 cases and 432 controls for further analysis.
The study found that:
the risk of inflammatory bowel disease was the same whether
for vaccinated or unvaccinated people
there was an average of 140 months between vaccination and
diagnosis for cases.
Only 1% of cases developed inflammatory bowel disease within
a year of vaccination
Only 1% of controls developed inflammatory bowel disease within
a year of vaccination.
Whether children were vaccinated before 12 months, between
12 and 18 months, or after 18 months, showed no difference
in the risk of developing inflammatory bowel disease
However, the study team had to acknowledge several serious
limitations to this study:
Only patients with a physician diagnosis (usually a gastroenterologist)
were included. This could have potentially missed many cases,
particularly if those missed were of an insidious new variant
The team acknowledged the inherent limitations of diagnostic
accuracy in any retrospective study
They had little information on children or adults with non-specific
colitis that did not lead to an eventual diagnosis of IBD
- surely a key failure, given the nature of the research by
the Wakefield team at the Royal Free Hospital in London
There was an acknowledged limitation over statistical power.
The report admitted:: "We were able to effectively rule
out associations larger than 2-fold between ever being vaccinated
with MMR and developing IBD, and associations larger than
3-fold between vaccination with other measles-containing vaccines
and IBD. However, we had a limited sample size from which
to look at the independent associations between vaccination
and either Crohn’s disease or ulcerative colitis, or
at the relationship between timing of vaccination early in
life and subsequent risk for Crohn’s disease or UC."
This seems to be a serious self-criticism, yet oddly it does
not seem to have had much effect on the study’s assertive
The study’s reliance on patient records should also
be questioned. The analysis of records can by definition be
only as good as those records themselves. No study (as far
as is known) has yet endeavoured to verify whether children
suffering from acquired autism, ileal lymphoid nodular hyperplasia
or non-specific colitis have medical records that accurately
reflect these conditions. There are grounds for suspecting
that the very reverse may be the case. The difficulties in
obtaining a clear and timely diagnosis of autism are well
known. The nature of the autism problem, with many patients
without speech, means that the precise nature of the patient’s
complaints and symptoms may be poorly recognised, and even
more poorly recorded.
Overall verdict: although this study at first sight appears
more persuasive than some others, it too fails to provide
convincing evidence against an MMR/autism link. The study
may be seriously flawed due to its retrospective nature, when
the condition in question (acquired autism after MMR/MCV)
has only recently received publicity, and because of doubt
When it became apparent to Taylor, Miller and Farrington that
the time-lapse for degeneration into autism might be a protracted
one, they were obliged to re-analyse their earlier data.
Farrington, Miller et al repeated their view of the original
Wakefield study, that it was very small (12 children) and
that the interval between receipt of MMR and first behavioural
symptoms varied from 24 hours to two months. However, the
Wakefield study cohort subsequently grew to about 200, and
this has not been acknowledged by Farrington, Miller et al
in this further paper.
The Farrington, Miller et al study also has not taken account
of the Spitzer, Aitken et al study and its implications (see
later sections). They also maintain that they "found
no evidence to support a causal association". But they
themselves, in their first study, unconvincingly dismissed
a clustering of parental concerns at around six months. They
maintain this unconvincing stance.
Farrington et al concluded that the temporal association found
by Wakefield et al was "a combination of selection bias
and chance". This latter is a highly contentious conclusion,
suggestive of wishful thinking, in the same way as the dismissal
of the six-month clustering was.
In this second paper, the authors seek to re-test their earlier
conclusions by removing any preconceived fixed-time interval
between vaccination and the onset of autism. Again, they use
a statistical methodology, self-matched case-series analysis,
but once again with a very small (for this method) data set
of just 64 cases of what they describe as "unvaccinated"
children with autism - presumably, they mean "unvaccinated
with MMR" - plus 231 cases of children with autism who
had received one dose of MMR, and a further 62 cases of children
who had received two doses of MMR (total 357 children).
The study found that:
for the 357 cases, the observation periods had a median of
89 months, a maximum of 191 months.
The oldest age at diagnosis was 180 months.
Some 64 did not receive MMR.
Some 43 received MMR after age 2 years, at median age 57 months,
maximum 165 months.
Some 62 cases received a second dose of MMR, at median age
54 months, maximum 159 months.
The comparison of relative incidence for each group finds
that there is little difference between those that had received
MMR and those previously referred to as "unvaccinated",
but which seems to have really meant "vaccinated with
single-antigen measles vaccine" - the paper is not clear.
The major criticism of the earlier paper using this data (see
above section) were that there was only a proxy for "onset
of autism" (a questionable term in itself). The original
study measured diagnosis, parental concern and regression
(if applicable) from medical records. But these would be variably
delayed from any actual "onset event". The very
poor correlation between these proxies and the "event"
means that the analysis loses all statistical power.
Major criticisms of this further re-worked paper’s statistical
methodology are that:
Regarding the whole period following MMR as being "at
risk" is questionable.
Looking to see if those who have MMR earlier have a proxy
variable earlier is erroneous, when one observes the very
narrow timescale for the application of MMR in this paper.
When the input signal (the age of receipt of MMR) has very
little variability, one would be unlikely to find this reflected
in the output signal (date of diagnosis)
The above flaw means that the only statistical power left
is coming from finding any difference between those who have
MMR and those who have not. But most of those who do not have
MMR are those older children who are of the pre-MMR generation.
So Farrington et al’s analysis is effectively asking
whether those who are older had had an earlier or later onset
of autism (as measured by the proxy variables).
Overall verdict: this study fails to provide any convincing
evidence against an MMR/autism link.
This paper examined whether there is a new phenotype of autism
involving regression and gastrointestinal symptoms.
It is suggested that where this paper is flawed is in the
assumptions underpinning the hypotheses that are tested. All
else stems from that. Fombonne & Chakrabarti assume that
if autistic enterocolitis existed, then one or more of the
following six predictions should be supported by empirical
Prediction (1) - "childhood disintegrative disorder has
become more frequent". (The study found the prevalence
of childhood disintegrative disorder to be 0.6/10,000, or
1 in 16,666. But this seems far too low in comparison with
other recent studies).
Comment - historic data is not available to prove this either
way. The claim that the present rate of 1 in 16,666 represents
no increase is further undermined by its non-credible low
level. Other studies have found rates very many times higher.
This strongly suggests that the study is flawed.
Prediction (2) - "the mean age of first parental concern
for autistic children who are exposed to MMR is closer to
the mean immunisation age than in children who are not exposed
Comment - the study found that there was no difference in
the mean age at first parental concern between the two samples
exposed to MMR (19.3 months and 19.2 months) and the pre-MMR
sample (19.5 months). But no argument has been presented as
to why there should be a difference. A difference might be
expected, but its absence in itself does not prove anything.
It is perfectly possible that childhood disintegrative disorder
has several causes, and that the arresting of development
could be noticed at around the same time. Pre-MMR children
who became autistic may well have become so due to an adverse
outcome from monovalent measles vaccine. This possibility
does not seem to have occurred to Fombonne. There is also
a simplistic focus upon MMR alone as a sole factor, working
in isolation, rather than as part of a complex process.
Prediction (3) - "regression in the development of children
with autism has become more common in MMR-vaccinated children."
The study found that the rate of developmental regression
reported in the post-MMR sample (15.6%) was not different
from that in the pre-MMR sample (18.4%) and therefore there
was no suggestion that regression in the development course
of autism had increased in frequency since MMR was introduced.
The study also found that in the epidemiologic sample, the
subset of autistic children with regression had no other developmental
or clinical characteristics, which would have argued for a
specific etiologically distinct phenotype.
Comment - the samples were small. The study used three samples,
a post-MMR sample of 96 children with PDD, a pre-MMR sample
of 98 autistic patients, and a post-MMR sample of 68 autistic
patients. These are very small numbers to use in a statistically-based
study. Fombonne and Chakrabarti’s results should thus
be treated with caution, as a few cases either way would impact
upon their conclusions.
Prediction (4) - "the age of onset for autistic children
with regression clusters around the MMR immunisation date
and is different from that of autistic children". The
study found that parents of autistic children with developmental
regression detected the first symptoms at a very similar age
(19.8 months) to those of autistic children without regression
(19.3 months). The study also found that the mean intervals
from MMR immunisation to parental recognition of autistic
symptoms were comparable in autistic children with or without
regression (248 days vs 272 days, not significant).
Comment - but regression would not be expected to "cluster
round", but may follow MMR at a delay of weeks, months
or years. There is no scientific justification for assuming
that children with regression after MMR should have their
condition recognised at a different time to those who did
not regress after MMR. In any event, it is stated that the
difference between 248 days and 272 days is not significant,
but it is almost 10% different, and this difference has not
Prediction (5) - "children with regressive autism have
distinct symptoms and severity profiles."
Comment - little scientific justification for testing this
assumption is given in the study, which also refers to external
features such as behaviour, when the real focus of interest
should be on gut biopsies and ileocolonoscopies of the actual
children, which of course were not done in this study. Not
enough is known about autistic enterocolitis to make such
an assumption about external characteristics into a key test.
Prediction (6) - "regressive autism is associated with
gastrointestinal symptoms and/or inflammatory bowel disorder".
Comment - but the children in this study did not undergo ileocolonoscopy.
Their condition was medically unresearched.
this is a statistical analysis of random groups of children,
not of the children whose cases are going to the High Court.
The numbers are extremely small, too small for a reliable
interpretation to be made
The assumption seems to have been made that children could
not have been damaged by vaccines other than MMR. The Lassiter
court case outcome (US) means that there is evidence, that
has been accepted in a Court that other multiple vaccines
also trigger autism.
What this study set out to do was not to investigate the cause(s)
of damage to specific children, but to clear MMR of any complicity.
At first sight, it succeeds in the latter, but at closer analysis,
it makes numerous unfounded assumptions that considerably
weaken the strength of its conclusions. At worst, it demonstrates
the central flaw of designing a study hoping to achieve a
desired outcome, rather than to investigate a problem.
Overall verdict: this study fails to provide any convincing
evidence against an MMR/autism link.
The objective of this paper was to investigate whether MMR
vaccination was associated with bowel problems and developmental
regression in children with autism, and to look for a "new
variant" form of autism.
Some 278 children with what the authors defined as "core
autism", and a further 195 with "atypical autism"
were studied. These were identified from disability registers.
The children were born 1979-1998.
The outcome measures that were studied were:
Recorded bowel problems lasting at least three months
Age of reported regression (where it was a feature)
Relation of these to MMR
Of the 473 children whose records were reviewed, 81 (17%)
were reported to have associated bowel problems, comprising:
42 with constipation
7 with constipation and diarrhoea
19 with diarrhoea
7 with food allergy
2 with non-specific colitis with ileal-lymphoid nodular hyperplasia
(4 noted as "others")
The study reported that:
The proportion of children with developmental regression (25%
of the overall) or bowel symptoms (17%) did not change significantly
during the 20 years from 1979 (MMR being introduced in October
No significant difference was found in rates of bowel problems
or regression in children who received the MMR vaccine before
their parents became concerned about their development, compared
with those who received it only after such concern, and those
who had not received MMR.
A possible association between non-specific bowel problems
and regression in children with autism was seen, but this
was unrelated to MMR
The study concluded that its findings provided no support
for an MMR-associated "new variant" autism, and
further evidence against involvement of MMR
The study admitted that it had the "strengths and weaknesses
of data based on case notes. Data was not recorded systematically
and there was variability in the level of detail."
Comment - there are several major criticisms that can be made
of this study.
Most importantly, it was an epidemiological study of case
notes, not a clinical study (with examination and clinical
analysis of samples) of the cohort of children believed to
have been damaged.
No clinical examination appears to have been undertaken by
the study team, and it is highly questionable whether such
examination or analysis was ever undertaken in the past by
paediatricians or specialists in the field, either. This greatly
reduces the value of this study.
Equally importantly, the study relies heavily upon the accuracy
of child health records. Experience suggests that the health
records of autistic children do not accurately reflect their
condition, with numerous specialists and agencies involved
and with the records not necessarily accurately reflecting
the information supplied by parents, due to poor reporting,
poor recording and undervaluing of parental "anecdotal"
For health records to be relevant to an assessment of a novel
syndrome, which was first only widely reported in 1998 (and
has been repeatedly denied by the Department of Health ever
since), health professionals would have to connect what the
parents were reporting, and the condition of the children,
with the new syndrome. They would also then have to have commissioned
appropriate clinical examination of the children, and ensured
that this was accurately recorded.
It is patently obvious that this would not have happened for
the perhaps the first nineteen of the twenty years 1979-1999.
The study is therefore trying to assess records made in an
era before in-the-field awareness existed, and in all probability
without any appropriate clinical examination or analysis ever
having taken place in the past, as well as during the study.
These major criticisms would appear to leave the study seriously
lacking relevance. Despite this, the study was described by
the Department of Health as "elegant".
The independence of the study also must be questioned.
Dr. Elizabeth Miller, head of the Immunisation Division of
the Government’s Public Health Laboratory Service, was
a direct participant at the Department of Health’s re-launching
of the MMR programme in January 2001, and thus cannot be regarded
as a detached "outside" researcher.
And as long ago as December 1997, Professor Brent Taylor described
Dr. Andrew Wakefield, in writing, as "a zealot.....who
thinks that MMR is the cause of all the problems of the Western
world." This suggests that Taylor’s stance towards
the alleged MMR/autism issue was set several years ago. Researchers
are entitled to their views, but, if these are expressed in
such a highly charged manner, then it is only right that such
prior remarks should be set alongside their study findings,
particularly when such findings are regarded, and publicised,
by Government as an "independent" study.
There are other serious methodological criticisms of this
latest Taylor, Miller study:
The study looks at percentages of autistic children, giving
the impression that background rates of autism aren’t
increasing. What the study findings should also include is
a plot of the actual numbers of cases diagnosed per year,
and of inflammatory bowel disease/other aspects. This is a
crucial omission. It is impossible from the study report to
tell whether these numbers (as opposed to percentages) have
changed over time.
The study does not reveal the sample sizes for each year.
How many children fall in each year is not shown. It also
therefore does not confirm whether the distribution is even,
across the years. This makes the data impenetrable to outside
scrutiny. (Note: on ITV’s "Dimbleby" discussion
programme on 10th February, Prof. Taylor was challenged by
the National Autistic Society to release his raw data for
independent analysis, and declined to do so).
Following on from the above, any logistic regression on year
of birth is going to be highly underpowered as a way of detecting
any MMR effect.
The study does not make clear exactly how many of the 473
had MMR how many times, and precisely when. This is a fundamental
failure in methodology.
Notably, the study does not take the most obvious route of
all, of comparing a large group of MMR-vaccinated children
(10,000+) with another large group (10,000+) of unvaccinated
children. An epidemiological study could have been undertaken
of such groups. A study of only 473 children is far too small
to detect relatively-rare adverse outcomes. The study size
is so small that in some years there may have been no more
than a handful of children.
(Note: the study by Wakefield O’Leary et al looked at
about 200 children, but this was a clinical study, not an
epidemiological study. A cohort of 200 children in a clinical
study is vastly more reliable than a cohort of 473 children
in an epidemiological study).
As only 17% of the sample had "not had" MMR, and
only 18% had "reported bowel problems", this means
that the study inevitably is not very powerful.
According to Taylor Miller et al, their study identified just
two children with ileal-lymphoid nodular hyperplasia, the
novel syndrome being studied by Wakefield et al. This is either
wholly inadequate because it is such a tiny sample, or it
alternatively suggests that the case-notes missed many cases
amongst the remaining 473 cases. It would be extremely surprising
if the ILNH condition being studied by Wakefield only occurred
in 2/473 children. What this suggests is that very few children
out of the 473 have been clinically investigated to ascertain
whether or not they have ILNH.
The cohort of children identified by the study as having "bowel
problems lasting three months" is highly unspecific and
vague. Records would be most unlikely to accurately reflect
the extent, intensity, nature or length of time these "problems"
The percentage of "regressing" children is identified
as being 25%, yet Simon Baron-Cohen’s CHAT system uses
a rigorous definition which gives a rate of 10%. This difference
suggests that the Taylor Miller definition may have been unusually
"Parental concern" is not defined. It is not clear
whether this equates to a visit to the GP, or to personal
parental doubt. It is unlikely that health records would accurately
reflect this, particularly if onset was insidious.
Perhaps the most interesting finding is that there is a reported
highly significant association between developmental regression
and bowel problems. But as 87% had MMR, and only 31 had bowel
problems, one might expect 27/31 of those with bowel problems
to have had MMR, and 4/31 to have not had MMR. This again
has very little statistical power, because the numbers are
so very small as to be capable of being influenced by pure
chance, in addition to other methodological flaws described
elsewhere such as poor or inaccurate records.
It is also not clear which children that had "had MMR",
also had the booster as well as the early immunisation, the
booster but not the early immunisation, or the early immunisation
but not the booster.
The most extraordinary feature of this inconclusive study
was the way it was hailed as providing conclusive irrefutable
evidence that there was no link, despite is many serious drawbacks.
Its publication was met with a further claim by the Scottish
chief medical officer, Dr. Mac Armstrong, that any calls to
mount clinical studies into the MMR/gut/autism issue would
be "resisted". This line was repeated in a television
interview by Dr. Elizabeth Miller on 13th February 2002.
Conclusion: this study offers no evidence against an MMR/autism
This was held as a one-off in March 1998 to examine the Wakefield
team’s "Early Report" published in 2/98 in
The Lancet. It concluded
that there was no current evidence linking bowel disease or
autism with MMR
there was thus no reason, arising from the work considered,
for a change in the current MMR vaccination policy" (my
emphasis - note the careful wording)
This review has now been overtaken by subsequent events, yet
it continues to be quoted by the UK Department of Health,
as though time had stood still.
This paper reported on its review of MMR’s safety, based
upon a presentation by Dr. Elizabeth Miller of the Public
Health Laboratory Service on 24th July 2000.
There are a number of serious concerns about this paper:
The conclusion of the APPG and its invitees was that MMR was
safe, and that concerns about the alleged links with autism/inflammatory
bowel disease were unfounded. However, this is a very strong
claim, in the absence of appropriate comprehensive studies.
If a link is "unproven", that does not necessarily
mean that a concern is therefore categorically "unfounded".
Dr. Miller had demonstrated that MMR has enabled "excellent"
control of measles, but that is not the point at issue.
There was concern at the fall in MMR take-up. This, too, is
not what is under scrutiny. It is MMR’s safety that
is in question. Concern over measles outbreaks and falling
take-up may be legitimate, but are arguably being used here
as a form of moral pressure.
The APPG expressed concern about measles outbreaks elsewhere,
e.g. Holland. The same comment applies. It is MMR’s
safety in the UK that is under scrutiny.
The statement that "all (hypotheses about a link) have
originated from a single group of workers in the UK"
(at the Royal Free), and "none has been endorsed by independent
recognised medical experts anywhere in the world" is
highly misleading. The Royal Free team have been at the forefront
of research, but their work has been given backing by other
researchers (to give just one example, the letter in the Lancet
by Sabra, Bellanti and Colon, 1998), and the possibility of
a link has been endorsed, or has been unable to have been
ruled out, by other researchers. Other studies and reviews
have been inconclusive either way. The position is still one
of scientific uncertainty.
Claims that the Joint Committee on Vaccination and Immunisation
"is composed of independent clinical and scientific experts"
are open to question. The JCVI does not include gastroenterologists
- which is the key area of science under scrutiny in this
issue. Its independence can also be questioned on two counts.
Firstly, a number of its members have declared financial links
with the pharmaceuticals industry. This could be argued to
part-compromise their independence. Secondly, there is a collective
professional interest in eliminating infectious diseases through
immunisation. Such a body is therefore not wholly "independent"
when it comes to assessing evidence for adverse side effects
from vaccines, particularly if it involves a syndrome which,
if acknowledged, could damage confidence in vaccines and lead
to a resurgence in communicable diseases.
The Committee on Safety of Medicines is also questionably
"independent". It is a matter of record that 37
members of the CSM had between them, at the end of the 1990s,
nearly 190 separate declared financial links with the pharmaceuticals
industry, about one-half of which were personal financial
links. Some of these links involve the manufacturers of MMR.
The 190 links include shareholdings, consultancies, research
funding and non-executive directorships. An impartial observer
would find that these links could arguably weaken any claims
The claim that "there is no evidence" (for a link)
is factually incorrect (see elsewhere).
Claims of "overwhelming evidence" (against any link)
do not address the inconclusive nature of many of the studies
involved. There is still no hard evidence against a link.
These studies also conflict with the direct first-hand accounts
of the parents of the children believed to have been damaged.
It is disappointing, if understandable, that the All Party
Group should produce such a report. The Group appears to have
been given a presentation of only one side of the argument.
This review too has been overtaken by subsequent events.
This was yet another review group which, upon failing to prove
that there was a link, then drew the unproven conclusion that,
because they could not find one, it automatically followed
that there was no link. Membership of the group was messrs.
McGregor (chairman), Driscoll, Frith, Jewell, Meade, Sewell,
Smith, Tedder, Ward, Wing, Wright. The sub-group met four
The group was to develop a strategy for further research,
monitor and steer future MRC support, and report at least
The subgroup recognised that the level of MRC support, particularly
for IBD (but why not autism?) was "relatively weak".
The subgroup found that the case for autistic enterocolitis
was unproven, and that the California autism increase "may
be due to wider definitions and increasing awareness",
though it offered no scientific evidence to support this comforting
It concluded that much remained unknown about autism and IBD,
that MRC support for research was weak, and that "between
March 1998 and September 1999 there had been no new evidence
to suggest a causal link" (again, note the careful wording).
For autism, its recommendations included:
Investigation of risk factors, large-scale epidemiological
studies concentrating on late-onset cases (this led directly
to the Professor Andrew Hall three-year study at London School
of Hygiene & Tropical Medicine, but seemingly, to little
Development of tests to investigate gastrointestinal involvement
in autism (no progress on this has since been reported)
Maintaining a watching brief for further evidence of any link
Despite the above, which implied continued vigilance, the
chairman was openly dismissive of even the possibility of
a link emerging, Professor Alan McGregor telling Reuters "We
see this as the end of the story" (Reuters, 3/4/00).
The Immunisation Safety Review Committee was asked to assess
not only the scientific plausibility of the hypothesised association
between MMR and autism but also the significance of the issue
in a broader context. In the IoM’s view, the plausibility
assessment involved two components:
An examination of the causal relationship between the vaccine
and the adverse event
An examination of any pathogenic mechanisms that support the
The IoM set out a number of important reservations regarding
the heavy reliance on epidemiological studies to prove/disprove
any MMR/autism link:
Studies may not have sufficient precision to detect very rare
occurrences at a population level
A poor understanding of the risk factors and a failure to
use a standard case definition may also hamper the ability
of epidemiological studies to detect rare adverse events
Since MMR is virtually universal in developed countries, elucidating
any association with adverse outcomes requires the creative
use of administrative and other data sets and complex research
The rarity of the individual autistic spectrum disorders,
and the difficulty in determining their exact onset, and therefore
the temporal relationship between onset and vaccination, makes
certain epidemiological study designs (e.g. cohort studies)
The IoM Committee concluded that the evidence favours rejection
of a causal relationship. However, the Committee also noted:
Its conclusion did not exclude the possibility that MMR vaccine
could contribute to autism in a small number of children
The epidemiological evidence lacks the precision to assess
rare occurrences of a response to MMR leading to autism
The proposed biological models linking MMR vaccine to autism,
although far from established, are nevertheless not disproved
In a critique of the IoM Review in Autism Research Review
International Newsletter, Vol. 15, No. 2, 2001, Dr. Bernard
Rimland of the Autism Research Institute stated:
The IoM did in fact NOT reject the hypothesis that MMR is
a possible cause of autism (the IoM review is regularly quoted
by the UK Department of Health as having "cleared"
MMR of any link with autism)
the IoM report actually supports, not refutes, what the parents
It should be the medical establishment’s burden to have
proved that the vaccines are safe, not the critics’
burden to prove them unsafe - a key point.
Two of those who issued the IoM press release had links with
the manufacturers of MMR
This review paper (by Elliman and Bedford) offered no new
evidence, as was the case with the supporting commentary (by
Dr. Elizabeth Miller), but simply re-presented previous work.
The main conclusions were:
Children are more at risk from separate measles, mumps and
rubella injections than from the combined MMR
There has been no research into the long-term effectiveness
of single injections (Comment - but, again, the point at issue
is the safety or otherwise of MMR, and damage to specific
children - not the effectiveness of single vaccines)
The study authors acknowledged the receipt of funding from
vaccine manufacturers to attend meetings and conduct research.
Dr. Elizabeth Miller’s commentary included an attack
on The Lancet for publishing the 1998 Wakefield "Early
Report": "Publication in respectable medical journals
of (these) papers.....is a disservice to patients and health
professionals alike". Dr. Miller’s commentary included
the quote that MMR’s "safety evidence is so overwhelming".
The Department of Health welcomed this latest "research"
(which it was not), stating that "single vaccines would
put children at unnecessary risk and would have no scientific
The Elliman and Bedford paper did not review the work of Singh,
The UK Department of Health and Medical Research Council jointly
announced on 5th March 2001 that the DoH has asked the MRC
to conduct a detailed review of the current state of knowledge
The review was chaired by Professor Eve Johnstone of the University
of Edinburgh and Royal Edinburgh Hospital. The review was
to suggest possible areas for further research development,
including obtaining a clear and comprehensive picture of what
is currently known about the incidence, prevalence and causes
of autism, and how strong the evidence is which underpins
The main findings of the review, reported in December 2001,
It found no association between autism and MMR (this was later
misrepresented by the UK Department of Health as equating
to "clearing" MMR and "proving" that there
was no link - which the review did not)
The prevalence of autism is higher than had been thought (a
rate of 1/166 was quoted)
The review claimed to have had "extensive" input
from lay people. However, several refused on the grounds that
at least four of the expert-group participants were already
signed-up to the MMR manufacturers as paid witnesses in the
forthcoming UK High Court cases. There was also strong concern
from the outset from parents about balance in the review and
Most of the increase in autism was "explained" away
by changes in definition and increased awareness. The report
thus heavily played down any uncomfortable conclusion that
the increase might be real
Autism was found to result from several causes, with a genetic
component. The interplay between genetic and environmental
factors "was not yet known".
The review accepted that a number of studies (reviewed elsewhere
in this briefing note) offered "evidence" that there
was no MMR/autism link, or alternatively, did not offer evidence
to the contrary.
Various priorities for further study were identified,.
What was most notable in the review’s report was how
few studies for/against an MMR/autism link were covered at
all, seven at most against a link and only one (plus Wakefield)
For "evidence" against a link, the review reported
on just a handful of scientific studies - Taylor, Miller et
al, Kaye et al, Smeeth et al (which had yet to report), De
Wilde et al, Fombonne & Chakrabarti, Dales et al, and
Patja, Peltola et al. Each of these studies is covered elsewhere
in this briefing note, and each is shown to be flawed or inconclusive
in its outcome. Yet the MRC review accepted all of these as
"evidence" of no MMR/autism link.
For evidence for a link, even less satisfactorily, the MRC
rejected the hypothesis of Wakefield et al, and reviewed only
one scientific study to support an MMR/autism link, this being
Spitzer, Aitken et al (also reviewed elsewhere in this briefing
note). The only conclusion the MRC drew from this study, which
would of course have been in conflict with the MRC’s
no-link conclusions, was that the average age at diagnosis
of UK children with autism was 4 years.
By disparaging the possibility of any link between MMR and
autism, the review was able to sidestep having to suggest
any research in this area. So "no evidence" meant
"no future studies" in this controversial area -
and "no future studies" will thus ensure "no
evidence". It was clearly desirable for the MRC to avoid
raising further concern about MMR in its conclusions.
This found that:
Scientific evidence from epidemiological studies on whether
asthma and allergy can be caused by multiple vaccinations
was conflicting, and that the evidence "was inadequate
to accept or reject a causal relationship"
Epidemiological studies to date favoured rejection of a causal
relationship between multiple immunisations and increased
risk for infections and for type 1 diabetes
There was some biological mechanism evidence that vaccines
could increase the risk of immune dysfunction in some children,
that could lead to increased infections and allergy, including
asthma. The IoM stated that "the biological mechanisms
evidence regarding increased risk for infections is strong".
On vaccine-induced neuroimmune dysfunction, the IoM Committee
"The Committee was unable to address the concern that
repeated exposure of a susceptible child to multiple immunizations
over the developmental period may also produce atypical or
non-soecific immune or nervous system injury that could lead
to severe disability or death. There are no epidemiological
studies that address this. Thus the Committee recognises with
some discomfort that this report addresses only part of the
overall set of concerns of some of those most wary about the
safety of childhood immunizations"
The Committee also expressed a new note of caution: "As
the array of available vaccines and disease-targets expands,
the current emphasis on universal recommendations and on State
mandates for vaccine use should be re-assessed".
A critique of the IoM report by the US parents’ group
PROVE pointed out that the report was drawn up only after
a review of past literature, and did not involve new research,
and that many of the authors of these past studies had conflicts
of interest. Conflicts of interest were also held by some
of those that contributed "constructive criticism"
to the report, and some researchers who had identified links
between autoimmune conditions and vaccines had not been permitted
to make presentations to the IoM Committee.
This section looks at a review of the original evidence for
MMR’s safety, published by Wakefield and Montgomery,
subsequent comments from other researchers, and the response
of the manufacturing industry and the UK Department of Health.
(Note: it is worth stating the obvious, that it should be
for the manufacturers to prove that their product is safe,
not for the parents of damaged children to prove otherwise
- though this latter is what is now in effect occurring.)
Wakefield & Montgomery reviewed the following safety studies:
Buynak et al 1969, Stokes et al 1971, Minekawa et al 1974,
Schwartz et al 1975, Crawford and Gremillion 1981, Miller
et al 1987. The following is an abbreviated summary of their
The Buynak study identified viral "interference".
The follow-up period was only 12 days
The Stokes study revealed persistent gastrointestinal problems
in the US trial children. The follow-up was only 28 days.
Stokes compared 228 MMR children with 106 unvaccinated controls.
Data, from Philadelphia and Costa Rica and San Salvador, was
merged - a serious methodological error.
Gastroenteritis was found to be significantly more common
in the Philadelphia vaccinees (24%) compared with the unvaccinated
Philadelphia controls (5.6%). No significant difference was
found between the vaccinated and the unvaccinated in Costa
Rica and San Salvador because of high levels of gastroenteritis
anyway (50% in vaccinees, 44% in controls). Combining all
the data masked these instructive differences.
There was also significant "unrelated" illness in
39% of Philadelphia vaccinees (otitis, allergy, viral infection,
abdominal pain), compared with 12.2% in controls. The potential
relevance of this was not seen at time.
The Minekawa study confirmed viral interference. The follow-up
period was only 15 days.
The Schwartz study also merged its data, so provided insufficient
insight. Follow-up was only 21 days. The study looked at two
different populations, 282 children in Ohio and 926 children
in Santo Domingo, Dominican Republic. Again, the merging of
data from different countries was a serious error. No data
was provided to permit analysis of adverse events.
Crawford and Gremillion’s study of USAF recruits confirmed
viral interference. The follow-up period was only 19 days.
Some 512 vaccinees were compared with 835 unvaccinated controls.
The study noted increased fever and diarrhoea in those that
received measles and rubella vaccines simultaneously. But
the potential effect of trivalent vaccine was not additive
but synergistic - a key point.
The Eddes study (a small UK study) 1991 compared reactions
to MMR with monovalent measles vaccine. High rates of gastrointestinal
disorders (41.9% and 37.8%) were found. The authors dismissed
these as normal background illness.
The Miller study noted that diarrhoea was common (26% of vaccinees).
The follow-up was only 21 days. This was a major missed opportunity
to follow up a large cohort. (NB this was Dr. Elizabeth Miller,
who has been so vociferous in criticising the Wakefield findings
and in defending MMR, and who was co-author, and designed,
the heavily-criticised 1999 Taylor, Miller North London study)
The Stokes, Schwartz, Miller and Eddes studies were therefore
all too small or too superficial to pick up uncommon adverse
The Plesner et al study of gait disturbance following MMR
(Acta Paediatrica, 2000, 89, 58-63) confirmed an association,
and indicated that more severe cerebellar ataxias following
MMR may be associated with residual cognitive deficits.
It is also worth noting that the Wakefield and Montgomery
paper is actually an argument for vaccination - but not using
triple measles-containing vaccines. Wakefield and Montgomery
are not anti vaccination per se. They argue that their duty
is to the patient. Dr. Wakefield has been investigating the
children brought to him, not campaigning against the UK DoH
for its own sake. He is simply relating what he is finding.
The peer review comments on Wakefield & Montgomery paper
were very powerful. Peer reviewers included Dr Peter Fletcher,
former Principal Medical Officer in the Medicines Division
(now MCA), who was medical assessor to the Committee on Safety
of Medicines. These are some summaries of his comments:
"Evidence on safety was very thin", and "Too
few children were followed for a sufficient time"
"Big numbers were necessary, and computerised databases
were already in place to permit this, but it was not done"
"Caution should have ruled the day", and "There
should have been strong encouragement to conduct a 12-month
observational study on 10,000-15,000 children" (this
was not done)
"The granting of a product licence was premature"
A subsequent letter was published in the Journal of Adverse
Drug Reactions & Toxicology, 2001 20(1) from Dr. Stephen
Dealler, Consultant Microbiologist at Burnley General Hospital,
Lancashire UK. Dr. Dealler stated:
The finding that measles virus ribose nucleic acid (RNA) in
the gut wall of almost all the autistic children that had
not suffered measles but had received MMR, when compared to
non-autistic controls (O’Leary, Dublin) must be investigated
Research in the US showing that inflammation can be found
not just in the large bowel and terminal ileum but in the
duodenum and jejunum as well should not be ignored
Data must be found to determine whether the measles virus
is actually causative, or merely retained because of inflammation
as a result of some other factor
Autism that might be produced will not necessarily appear
at a specific point after vaccination
Complex long term control trials may be required to show MMR
to not be involved in the pathogenesis of autism
Research into the background pathogenesis of autism is currently
In a further letter to the Journal of Adverse Drug Reactions
& Toxicology, Dr. F. Edward Yazbak MD FAAP and Kathy Lang-Radosh
MS of TL Autism Research, Falmouth Massachusetts, stated that:
Many children with the new or acquired autism syndrome are
normal until past their first birthday, and then develop symptoms
in the second or third year of life, or even later
These children actually lose previously-acquired skills
Children with the new autism have gastrointestinal, neurological,
sensory and endocrine difficulties
They also have an inordinate number of infections, for which
frequent and repeated courses of antibiotics have been used,
often leading to candida overgrowth, with further consequent
damage to the gastrointestinal tract and increased ileal permeability
Additionally, sulphur transferase deficiency in certain children
with autism causes decreased sulphating, which results in
inadequate detoxification and reduced mucin formation, which
further compromises mucosal integrity. The result is excessive
absorption of noxious polypeptides
While recent research has pointed to a genetic contribution
of autism, a more likely aetiology of the apparent familial
aspects of autism may simply be a family predisposition to
The Through A Glass Darkly safety paper by Wakefield and Montgomery
was strenuously criticised by Mike Watson, Medical Director
of Aventis Pasteur MSD, the manufacturers of MMR.
But Watson’s criticisms do not themselves stand up to
scrutiny, as demonstrated below by Paul Shattock of the University
of Sunderland Autism Research Unit. The only aspects that
cannot be bottomed-out by Shattock are where the studies referred
to by Watson have not been published.
Watson maintains that observation period in trials (as reported
in paper by Stokes et al, 1971) was up to 63 days, not up
to 28 as reported by Wakefield. However, Shattock quotes Stokes
study as saying "Joint involvement was noticeably absent
during six to nine week follow-up....Present studies with
queries at six to nine weeks following vaccination did not
reveal any occurrence of arthritis or arthralgia beyond the
28-day period for close observation". The trial was therefore
28 days, with only queries for arthritis etc beyond this.
The Wakefield version is therefore correct.
Watson maintains that "MMR I" safety was investigated
in four studies prior to licensing in US 1971 and UK 1972.
Also, "MMR II" investigated by seven studies, two
of which published. Immruvax also tested in seven studies.
But Shattock questions whether studies are published or secret.
Wakefield & Montgomery can only comment on what is published.
Watson states that virologists generally accept wild measles
virus only causes persistent disease in central nervous system,
as subacute sclerosing panencephalitis (SSPE) or measles inclusion
body encephalitis (MIBE). Wakefield maintains potential for
delayed intestinal pathology has been borne out by Fournier
et al, 1968. Shattock response: the technology has failed
to isolate measles virus RNA in affected children, but further
progress is expected.
Watson states that mutant measles virus genetic material can
persist in tissues of apparently healthy people without causing
disease (Katayama et al, 1998). Shattock response: so mutant
measles can persist but vaccine strains cannot? - challenge
for evidence to substantiate this claim.
Shattock also makes the important points that (a) MMR test
group in Stokes 1971 paper had way more GI problems than controls,
(b) that in Schwartz et al paper 1975 the results of 282 children
from Daytona Ohio and the 1192 from Santo Domingo and Panama
were pooled (unscientific), and (c) why was gastroenteritis
completely omitted from list of side effects when difference
of incidence between groups were so blatant?
Watson: "gold standard" in safety studies was placebo-controlled
crossover study of 1162 twins in Finland 1982. More detail
published by Virtanen, Peltola et al 2000. Shattock response:
was the 1982 study published?/where? Also, the 2000 Peltola
paper was actually only published after Wakefield & Montgomery
Wakefield: follow-up interval reduced from 4 weeks in initial
controlled trial to 3 weeks in subsequent trials. Watson:
insists follow-up was up to 63 days. Shattock response: observations
were for 28 days. At up to 63 days, parents asked about any
significant illness - side effects listed in paper apparently
excluded. No doubt Wakefield’s 28 days is right.
Watson: later MMR II studies had observation period of 42
days. Priorix studies had periods of 42-60 days. Shattock
response: where are publication details?
Watson: numerous post-marketing studies of MMR have been conducted
and published. Shattock response: references please? Why haven’t
they been quoted by DoH, why can’t anyone find them?
Other "facts" quoted by Watson in "Aventis
Pasteur MSD - Vaccines For Life" paper:
Watson: "national safety regulators require all side
effects to be reported". But this doesn’t mean
they actually are, especially in a novel syndrome with (up
till 1998) no publicity, delayed onset, and an official refusal
to count reports as an "adverse reaction"
Watson: "there have been over 500m doses given worldwide".
But there are also many hundreds of thousands of cases of
autism worldwide, and none of these has been admitted by authorities
to be consequence of MMR, thereby keeping its safety record
Watson: "As anyone in clinical trials knows, all participants
or their parents are very carefully informed and consented".
Yes, but this wouldn’t have covered a warning to watch
out for subsequent delayed degeneration into autism!
Watson: "Any unusual event that occurs in that child
at any time after trial should be reported to MCA". But
this would almost certainly never have included autism pre-1997,
when very first publicity was given in Pulse magazine and
BBC Newsnight. (NB: In Oliver Thrower’s case, the BBC
TV Newsnight report of 8/97 was the first clue, nine years
after vaccination, as to the cause of his autism. In his case,
vaccination had never previously been mentioned or considered
as a possibility by health professionals. He was added to
the UK Medicines Control Agency database 11 years after vaccination.
So much for the value of even a 63-day trial follow-up!)
Watson: "An unimmunised child is the infectious equivalent
of a drunk driver". This comment is a revealing insight
of the industry’s "MMR or be damned" culture.
Watson: "Giving vaccines separately would be more expensive".
More expensive than all the extra health costs, care costs,
special education costs, special needs transport costs, lost
earnings of the victim, lost tax revenues, parents’
lost earnings and taxes?
Quote from MSD product insert on MMR: "Clinical studies
of 279 triple seronegative children, 11 mths to 7 years of
age, demonstrate that MMR is highly immunogenic and generally
well tolerated." (So is just 279 the number?)
The UK Department of Health’s response was summarised
in its press release of 21st January 2001. The main points
are set out below, with the DoH’s text in italics, and
with my own responses following.
The claim by Wakefield & Montgomery that there was insufficient
research "is factually incorrect, as many studies recorded
safety data up to six weeks, which is standard for vaccines,
and some studies recorded data for longer - up to a year in
some cases". Yes, but autism did not form part of this
surveillance, the importance of gastrointestinal problems
was not appreciated, the reference to six weeks being "standard
for vaccines" doesn’t address the autism/gut syndrome,
and very few cases indeed, in very few studies indeed, were
followed up for longer than a few weeks. Thus the syndrome
"Combined MMR vaccines had been extensively tried and
tested in Scandinavia and the USA before they were introduced
in the UK in 1988". As a statement, this proves nothing.
The new syndrome of autistic enterocolitis was not suspected
in these countries, either, and again was missed.
"Now MMR is successfully used in over 30 European countries
as well as the USA, Canada, Australia and New Zealand".
The same comments apply. There is an autism problem in all
these countries too. Perhaps MMR is implicated elsewhere outside
"A publication in 1988 lists 30 published studies where
combined MMR vaccines were studied and follow-up was extended
up to ten years". The same comments again apply. (See
also the Wakefield/Watson/Shattock rebuttals section)
"The safety of combined MMR vaccines has been reviewed
repeatedly by the Government’s independent expert scientific
advisory committees including the Committee on Safety of Medicines
and the Joint Committee on Vaccination and Immunisation".
This is true in a purely literal sense, but the reviews have
been mis-designed and halfhearted or inconclusive (Quote:
"It was impossible to prove or refute the suggested association
between MMR vaccine and autism/pervasive development disorder
or inflammatory bowel disease because of the nature of the
information, the self-selection of cases and the lack of comparators"
- Committee on Safety of Medicines Report of the Working Party
on MMR Vaccine, page 12, paragraph 5.5).
One can also strongly argue that the Committees quoted are
neither wholly independent (see other references) nor expert
in the field of gastroenterology, as opposed to immunology.
"The use of MMR vaccine is also endorsed by the World
Health Organisation, the British Medical Association, the
Royal College of General Practitioners and the Royal College
of Nursing." This in itself proves little in the context
of an intense scientific debate about a new discovery in gastroenterology.
The latter institutions may come to regret their endorsement
in the fullness of time. Have their advisers read all the
evidence, on both sides, first-hand? If the evidence either
way is fuzzy, do they give the benefit of the doubt to the
parents who allege their children degenerated, or to the vaccine
"By 2000, several hundred million doses will have been
given wordwide". Yes, and there will also be several
tens, or hundreds, of thousands of cases of autism worldwide,
some of which may have been precipitated by MMR.
In short, the DoH’s rebuttal sought to refute the Wakefield/Montgomery
paper, but was almost entirely couched in generalities. The
devil is in the detail of the Wakefield/Montgomery paper.
And the Department of Health was unable to refute this detail
- indeed, it largely avoided addressing it.
This paper reported that 3-4 weeks following an otherwise
uncomplicated first vaccination against smallpox, a boy then
aged 15 months and last examined at age 5.5 years, gradually
developed a complete Kanner syndrome (autism). The question
whether vaccination and early infantile autism might be connected
was being discussed.
It noted that "A causal relationship was considered extremely
unlikely, but vaccination is recognised as having a starter
function for the onset of autism" (my emphasis).
(Note: this paper is most notable for drawing attention to
a possible vaccination/autism link as long ago as 1976. If
such a link was recognised a quarter of a century ago, why
has so little been done since to research it?).
This reported a study by macrophage migration inhibition factor
test, in seventeen autistic patients and a control group of
eleven patients suffering from other mental diseases, of cell
mediated immune response to human myelin basic protein. It
of the seventeen autistic patients, thirteen demonstrated
inhibition of macrophage migration
none of the non-autistic patients showed such a response
the results therefore indicate the existence of a cell-mediated
immune response to brain tissues in autism
the noting of the potential relevance of antimyelin autoantibodies
reference to the work of Stubbs in the USA and the suggestion
that an inflammatory reaction in the brain may contribute
to the development of autism
references to indirect evidence of immune activation in autism
the reference to Singh’s finding, also in the USA, that
identified serum antibodies to myelin basic protein in 19
out of 33 autistic children, compared with only 9% in a control
reference to Todd and Ciaranello’s detection of circulating
antibodies in seven out of thirteen children with autism
This studied 40 infantile autistic patients ranging from 6-15
years, of which 22 were classical infantile autism ("true
autism", or TA) and 18 lacking one or more defects associated
with infantile autism and were therefore termed "pseudo-autism
syndrome" (PAS). Medical histories focused on possible
viral infection in the mother, especially during second trimester,
whether the child had multiple infections, especially otitis
media, in the first to fifteenth month of life, and the relation
of onset of symptoms to immunisation. Results were:
antibodies to myelin basic protein were present in 20 out
of 22 TA and 4 out of 18 PAS children
12/22 TA and 6/18 PAS children had a decreased response to
ConA and negative LIF response to PHA and a decrease in suppressor
functional assay (later studies showed a good correlation
of the above with low levels of CD8/CD28 and CD8/CD38 T-cells)
6/22 TA and 12/18 PAS children had increased toxic metal levels,
usually aluminium) and decreased levels of trace minerals
necessary for a normal immune response
10/22 TA and 6/18 PAS children had elevated thyroid stimulating
titers to rubella were ten times normal in 11/22 TA and 5/18
several of the children had elevated IgM levels to measles,
indicating a defect in immune regulation
Fudenberg states that:
the very low IL-2 receptor/positive lymphocytes and the decrease
in DR+, but not IL-2 receptor+ lymphocytes, suggests incomplete
activation in the TA children, a finding seen in other autoimmune
diseases; this suggests that TA may be an autoimmune disease
it is possible that "auto-antibodies" are directed
against various viruses and that the reaction to myelin basic
protein, neuron axone filaments, one or other receptors for
neurotransmitters, represent molecular mimicry
TA is probably due to adverse reactions to live virus or live
virus vaccine in a genetically-predisposed individual, one
whose cell-mediated arm of his/her immune system is not yet
mature, or, in a very young infant, by transplacental IgG
antibodies from a mother with high titers of antibodies to
one of the vaccine constituents, e.g. diptheria toxin
some children are susceptible to an environmental pathogen,
probably a virus or bacterium, resulting from an inherited
deficiency of their immune system
unable to clear the pathogen, the child is at higher risk
for the pathogen to damage the developing brain or trigger
an autoimmune response
the pathogen would not necessarily create gross neuronal damage,
but have more subtle effects on portions of the brain controlling
although not a requirement, the pathogen might persist and
replicate slowly or be maintained in homeostasis by the immune
Dr. Warren outlined the possibility of several key factors,
exposure to a certain pathogen at a vulnerable time, i.e.
at the time the central nervous system is undergoing rapid
the existence of an immune susceptibility or deficiency that
would allow a pathogen to persist
a genetic constitution that allowed certain T cells to react
to the pathogen in such a way as to cause reactivity against
the central nervous system or products of the central nervous
system such as neurotransmitters
in some cases an immune susceptibility or deficiency in the
immune system of the mother that may permit a pathogen to
be present in utero or allow an immune response within the
in some cases, a purported immune mechanism may have not caused
irreversible damage to the central nervous system but is only
interfering with brain function such as by binding to various
neurotransmitters or their receptors
In a study by Warren and Singh published in the journal Immunogenetics,
it was noted that:
of the 46 chromosones of 23 patients, 27 chromosones (58.7%)
had an extended haplotype as compared to an unrelated control
group in which 33/128 (only 25.8%) of chromosones carried
an extended haplotype
the frequency of extended haplotypes on chromosones of autistic
children was much greater than that on family-parent normal
chromosones, the latter being only 30.7%
in the initial and later studies, only eight out of 45 autistic
subjects did not have an extended haplotype, and fifteen autistic
subjects carried an extended haplotype on each of their chromosones
also, the mothers but not the fathers of the autistic children
had an increased representation of extended haplotypes
an additional control group of subjects with general severe
learning difficulties had a haplotype frequency of 26%, similar
to that of the earlier-mentioned unrelated controls
It was also noted that:
many normal individuals possess one or more of the above factors,
but it would only be those children that possessed all of
these, plus probably others, simultaneously, where autism
four season-of-birth studies had found an excess of births
in the month of March, and that, if a pathogen was involved
in autism, it was conceivable that it was more prevalent during
early winter so as to affect March babies
four to five times more boys than girls were affected by autism,
but that autoimmune diseases were often more common in one
sex, with the influence of sex hormones on immune functions
It was further noted there was a link between genetic background
and frequency of infections:
the products of the C4A and C4B genes are crucial to the activation
of the other vital components of complement involved in protection
against viruses, bacteria and other infectious agents
C4A proteins bind avidly to amino-rich surfaces and C4B proteins
form linkages with hydroxyl-containing carbohydrate surfaces
deficiency in the C4 proteins especially C4B has been associated
with increased viral and bacterial infection
inherited abnormalities of the complement C4 proteins are
linked to certain autoimmune diseases
This investigated the possible pathological relationship between
autoimmunity and autism, and reported that:
antibodies reactive with myelin basic protein (anti-MBP) had
been investigated in the sera of autistic children
nineteen out of 33 (58%) of sera of autistic children under
or equal to age ten were found to be positive for anti-MBP
in controls, only eight out of 88 (9%) were positive; controls
were age-matched and included normal children and children
with mental retardation or Downs Syndrome, as well as normal
adults aged 20-40.
This studied the immune responses to myelin basic protein,
which is a protein component of myelin. Defects in myelin
would dramatically affect brain activity. The study of 33
autistic children at or over ten years old was compared with
eighteen age-matched normal children. twenty children with
unknown-cause mental retardation and twelve children with
Down syndrome were also studied as controls, and testing for
serum antibodies to MBP undertaken:
antibodies were found in nineteen of the 33 (58%) of autistic
the corresponding level for controls was 7%, or over eight
testing of the autistic children showed features also found
in patients with autoimmune diseases such as rheumatoid arthritis,
insulin-dependent diabetes and multiple sclerosis
The features above included genetic predisposition, gender
imbalance (four or five times higher frequency in boys than
girls), major histocompatibility association, and immune activation.
The authors suggest that autoimmunity may be a critical factor
in the cause of autism.
They note that an essential part of the autoimmune mechanism
should involve antibody-mediated immune responses or antibodies
against the brain, and that other recent studies have found
evidence of antibodies to brain tissue antigens, such as myelin
basic protein, neurofilament proteins and serotonin receptor.
They also note that antibodies to MBP may have some pathological
relevance since abnormal cell-mediated immune response involving
a soluble factor but not antibodies to this protein has been
detected by other researchers, suggesting that autistic children
develop inappropriate immune responses to this brain protein.
They conclude that at present (1992) the relationship between
antibodies to MBP and autism was not understood, but they
hypothesised that the development of the immune response could
be the basis of autoimmune pathogenesis in some cases of autism.
It was conceivable that if an immunological assault was to
occur before birth or during infancy or early childhood, it
could lead to poor myelin development or abnormal function
of the nerve fibre myelin.
This found that:
among 16 children diagnosed with autism, there was a threefold
increase in their serum rubeola titers over the expected normal
the unusually high and persistent titers of anti-measles antibodies
in autistic children was statistically significant when compared
with a similar group of non-autistic subjects
it is suggested in the paper that MMR may play a role in the
pathogenesis of autism because elevated titers of anti-measles
antibodies may signify a chronic over-activation of the immune
This found that
brain regions whose pre-vaccination neuronal damage had been
relatively insignificant may, via vaccine-induced clonal expansions,
suffer additional damage.......resulting in vaccination-enhanced
neuropathy presenting clinically as autism
recent research findings are instructive regarding autistic
children for whom.......medical records show a history of
infections, antibiotic treatments, vaccinations and temporally-associated
onset of autistic traits.........
nearly any vaccine may have the potential for inducing neuronal
damage in persons with NdEs." (Source: Hypothesis: Infection,
Antibiotics, Vaccination-Induced Neuropathies; Mechanism Of
Pathogenesis In Some Cases Of Autism, ADHD, Tourette’s,
by Theresa C. Binstock, bit.listserv.autism 3rd January 1997)
although presented as a hypothesis, a route is offered that
demonstrates how a small subset of susceptible infants could
be affected, that a variety of vaccines could be involved
for this subset of cases, and that prior treatment with antibiotics
may play a critical role
This letter reported:
That there had been 24 notifications of temporary gait disturbances
after MMR vaccination
At a median of 6 days (range 3-25 days) after vaccination,
the children developed unsteadiness. Usually the children
recovered after a short time (median 8 days, range 1-100 days).
One child had not recovered after three months.
A possible cerebral disorder was reported in 8 children, with
unusual screaming in 5.
In company reports of MMR vaccines, gait disturbance was mentioned
as a rare complication.
Plesner et al later reported on a study of gait disturbance
following MMR (Acta Paediatrica, 2000, 89, 58-63)
This suggested a theory that high titers of rubella antibody
present in mothers of children with autism could be transplacentally
transferred and could persist in the child, and that when
the child received MMR, rubella antigen may complex with pre-existing
antibodies, thereby possibly playing a role in the pathogenesis
of autistic features.
This study involved the observation of 30 patients with post-vaccinal
pathology of the CNS and other symptoms, where the first symptoms
appeared concomitantly with or immediately after administration
of a vaccine. Patients were subjected to serological testing
for herpes virus (IgG and IgM) and to HLA (A, B, C) and HLA-DR-DQ
tissue typing to see if there was any correlation between
the emergence of CNS pathology and these antigens, to show
a possible autoimmune type immunogenetic basis for any demyelinisation
The authors reported that 30 Italian patients were observed
between April 1994 and October 1995. Clinical signs were dermatitis,
food allergies, constipation and reflux, and these followed
vaccination with the Salk or Sabin polio vaccine, DT, measles,
DPT, anti-tuberculosis or Hepatitis-B vaccines. All patients
had had convulsions with or immediately after vaccination,
with very high fever or diarrhoea. The patients were children
3-9 months old.
Results of tests showed that:
Serologic investigation for herpetic virus (IgG and IgM) were
positive in all patients for IgG and negative for all patients
Seropositivity (IgG) for Epstein-Barr virus was estimated
at 73.8%, for cytomegalovirus of 71.4%, for Herpes Simplex
virus of 47.6%, and for Varicella-Zoster virus of 21.4%
In all patients, diminished sideremia and a deficit of IgA
and IgG were noted
All of the patients had been normal prior to administration
of the first dose of vaccine. Physicians had administered
follow-up doses of vaccines, leading to stabilisation of conditions
presented, and progressive clinical deterioration.
Patients were also subjected to HLA tissue typing (A, B, C)
and serologic HLA DR-DQ to check a possible correlation with
the emergence of CNS pathology. These antigens indicated a
possible autoimmune immunogenetic basis for the demyelinisation
An increase in the HLA-A3 antigen was found (43.3% vs. 25%
in the normal population) and the HLA-DR7 antigen (48.3% vs,
24.1% in the population).
The presence of A3 and/or DR7 was observed in 22/30 (73.3%)
of the patients.
The authors noted the problems of molecular resemblance, of
discriminating between self and non-self antigens, and of
determining the function of the Class 2a CMI molecules.
They noted that any interference with the process of presentation
of the antigen can predispose to an autoimmune disease.
They also noted that "alterations which do not occur
can be due to the action of viral agents which compromise
the specific immune response, because of their resemblance
to the "self" tissue antigens.
The authors note that the consequence is persistence of the
infective agents and a tendency to provoke - through a marked
reaction - induction of an autoimmune disease. This can present
in conditions of marked reactivity to some viruses and to
In 66% of patients there was an obstinate constipation. In
31% there was proctic symptomatology with emission of mucus
The authors concluded that autoimmune pathology was more frequent
in countries where vaccination was more widespread, i.e. in
countries defined as "clean" from the virologic
or microbiologic point of view. They also noted that the use
of thiomersal in vaccines (see elsewhere) could demonstrate
the possibility of changes in the aminoacids of the molecules
which preserve the antigen.
This found that:
measles produces immune suppression which contributes to an
increased susceptibility to other infections
high-titred measles vaccines have been linked to increased
long-term mortality among some female recipients
vaccines can impair cell-mediated immunity by shifting cytokines
release into a Th2 pattern, thereby allowing intracellular
pathogens (e.g. many viruses) to be more successful
This noted that:
it was a well-established finding that a significant number
of people with autism have elevated levels of blood serotonin,
and the successful use of medications (potent serotonin transporter
inhibitors, or PSTIs) suggest the possibility that serotonin
plays a role in autism
the authors studied 86 people with autism and their parents
to examine whether the gene for the serotonin transporter
may contribute to the risk of autism. They found evidence
of a significant relationship
it was possible that the serotonin transporter gene HTT was
serving as a marker in linkage disequilibrium with a genomic
variant which was contributing to susceptibility to autistic
several lines of evidence suggested the serotonin transporter
as the most logical candidate gene, based on existing evidence,
but many other candidates could be considered on only slightly
the short variant at the serotonin transporter locus was found
to be preferentially transmitted from parents to children
with autistic disorder, and this provides preliminary evidence
that the serotonin transporter may serve as a susceptibility
locus in autistic disorder. This finding may contribute to
identification of other factors which add additively or in
a multiplicative manner
This found that:
measles virus and measles vaccinations impair cell-mediated
they also increase the likelihood of other viral infections
These researchers found that:
of 88 children immunised at six or nine moths with Edmonston-Zagreb
or Schwarz SW6 or SW9 strain of measles vaccine, mitogen-induced
lymphoproliferation was decreased at 2 weeks in the SW9 group
and at 3 months in all groups
this was negatively correlated with measles antibody level
at 3 months
CD8 T-cells, soluble CD8, neopterin and beta2-microglobulin
were increased at 2 weeks in the SW9 group
soluble CD8 and beta2-microglobulin remained elevated at three
therefore measles immunisation resulted in suppression of
lymphoproliferation, which was most evident in infants with
the highest antibody responses and most immune activation
This found that:
relative deficiency of T-helper type 1 (Th1) and cytotoxic
T lymphocyte (CTL) responses in early life is associated with
an increased susceptibility to infections by intracellular
this is likely to reflect a preferential polarisation of immature
CD4 T-cells towards a Th2 rather than a Th1 pattern upon immunisation
with conventional vaccines
This paper reported that:
The authors had evaluated the possible role of MMR in the
pathogenesis of autism by comparing rubeola titers in autistic
and normal children.
Amongst 16 children diagnosed with autism followed in their
clinical practice, it had been found that these children had
a threefold increase in their rubeola titers over the expected
normal range. These had been compared with the rubeola titers
from 13 normal controls.
Subjectively, parents had stated that their children’s
developmental milestones deteriorated following MMR vaccination.
The elevated titers of anti-measles antibodies in autistic
children may signify a chronic activation of the immune system
against this neurotropic virus. MMR may therefore play a role
in the pathogenesis of autism.
The purpose of this study was to determine any causal relationship
between acute encephalopathy and subsequent permanent brain
injury or death, following measles vaccine, mumps vaccine,
rubella vaccine, MR or MMR. The conclusion was that a causal
relationship may exist as a rare complication.
The study looked at children who received the first dose of
these vaccines 1970-93 and who then developed an encephalopathy
with no determined cause within 15 days
A total of 48 children (out of 403 claims submitted) aged
10-49 months met the criteria. Eight had died, the remainder
had mental regression and retardation, chronic seizures, motor
and sensory deficits and movement disorders. Symptoms were
clustered on days 8 and 9 after vaccination. The clustering
was accepted as suggesting a rare complication of measles
Of the 48, 1 child had MR, 30 had MMR, 2 had MMR plus DTP,
2 had MMR plus haemophilus influenzae type b (Hib), 4 had
MMR plus DTP plus oral polio vaccine (OPV), 1 had MMR plus
DTP plus OPV plus Hib
Two of the deaths were in previously apparently normal healthy
children, who then received MMR. Three deaths occurred 3 months
to 4 years later. One non-fatal case reviewed had eventual
hyperactivity and aggressive behaviour at age 5 years.
The authors thought that (1) the 48 cases represented under-reporting
from a passive system, but (2) most serious cases had been
captured by the system - a self-comforting point?
This is the "Early Report" that started the major
public debate in the UK and beyond about a possible link between
MMR and autism.
Dr. Wakefield and colleagues suggested that there could be
the possibility of a linkage between vaccination and autism
and other disorders. Although he was not in a position at
that time to present the published evidence of comprehensive
studies, initial findings suggested that the hypothesis was
The Royal Free Hospital group’s report found:
that there was patchy inflammation of the colon and swelling
of the lymph glands in the last part of the small intestine
in 39 out of 40 children studied that had developmental disorders.
All the children had previously gone through periods of normal
development, and most had acquired words and social skills
which were subsequently lost
most children had suffered either diarrhoea or alternating
periods of diarrhoea or constipation, frequently associated
with bloating, abdominal pain and poor appetite, and occasionally
the passing of blood
parents reported in some cases that certain foods made their
child’s symptoms markedly worse, and witholding those
foods improved behaviour. This implied that there could be
a syndrome that linked intestinal inflammation with developmental
disorders of the autistic spectrum, and could offer a vital
clue in understanding the origins of some forms of childhood
Dr. Wakefield also speculated that if the bowel was damaged
during a critical period of brain growth, an excess of peptides
could gain access to the developing brain, where these peptides
may not only influence behaviour but also brain growth and
development. The disease pathway was described as "speculative
but biologically plausible".
No hard evidence (in terms of the examination of actual affected
children or the disproving of this theory) to contradict this
hypothesis has been offered to date by the UK Department of
Health or others, and the Department has yet to offer evidence
of its own that degeneration into autism or the onset of inflammatory
bowel disease following vaccination is caused by some other
Note: the study only looked at 12 children. By the end of
2001, over 200 children had been examined. It has been reported
in the UK press that virtually all fitted the same pattern
as the original 12.
This study investigated the patterns of infection that are
risks for SSPE, early infection and a close temporal relationship
between measles and another infection, as potential risks
The data was from 7019 members of a nationally representative
1970 UK cohort study. The ages of five childhood infections
were recorded before the onset of IBD symptoms. Diagnosis
of IBD and insulin-dependent diabetes mellitus (IDDM) as a
control disease were identified by age 26 years. The results
Mumps infection before age 2 years was a risk factor for ulcerative
Measles and mumps infections in the same year of life were
significantly associated with ulcerative colitis and Crohn’s
disease, but not with insulin-dependent diabetes mellitus
These relationships were independent of each other and of
sex, social class at birth, household crowding in childhood,
and family history of IBD.
The study concluded that atypical paramyxovirus infections
in childhood may be risk factors for later inflammatory bowel
This stated that:
in support of the findings of Dr. Andrew Wakefield are several
behavioural and clinical features known to be related to the
central nervous system, such as infantile colic and attention-deficit
hyperactivity disorder, which have been related to food allergy
the US researchers had noted a striking appearance of ileal-lymphoid
nodular hyperplasia in patients with non-IgE-mediated food
allergy who had presented a range of conditions including
asthma and attention-deficit-hyperactivity disorder
examination of two cases with hyperactive disorders who were
intolerant to various foods, by colonoscopy of their terminal
ileum, had produced findings match those of Wakefield et al
ileal-lymphoid nodular hyperplasia lesions of the gastrointestinal
tract allowed the entry of antigens across the inflamed mucosa
of the bowel as a result of the reactive inflammatory response
in the adjacent lymphoid tissue of Peyer’s patches in
patients with non-IgE-mediated food allergies
the researchers proposed that similar mechanism(s) may be
involved in the pathogenesis of the central nervous system
dysfunction in the patients described by Wakefield et al
This paper suggested that:
a significant number of autistic children have positive titers
of measles and/or MMR autoantibody which is associated with
the presence of myelin basic protein autoantibody
Most autistic children with virus antibodies also had brain
The more virus antibodies they had, the more likely they were
to have the brain antibodies
None of the non-autistic children had brain autoantibodies
The strongest link was between measles virus antibodies and
anti-MBP, suggesting that exposure to the measles virus may
cause the immune systems of children with autism to attack
None of the autistic children in the study had had measles
in the past, but all had had MMR vaccine
a measles-related triggered autoimmune response to myelin
may play a pathogenesis role in the cause of autism in at
least a subset of cases
Singh commented that the most likely explanation for the connection
between autism and measles virus was that some autistic people
were genetically predisposed to the disorder. Measles or the
MMR vaccine may somehow prompt their immune systems to act
in a negative way whilst leaving other people unharmed.
Singh stated that, of 88 autistic cases that he had examined,
51% said that their child’s autism had followed MMR
vaccination, and 36% had said it had followed DPT vaccination.
This paper noted that measles virus nucleoprotein (N antigen)
had been detected in association with follicular dendritic
cells (FDC) in patients, and sought molecular confirmation
of this result. It found that:
Solution phase RT PCR yielded specific MV N gene amplification
in affected children (10/10)
Distinct measles virus genome was identified in FDC reactive
follicular centres by in-cell RNA amplification
None of the normal controls showed any evidence of measles
The data highlighted a possible causal link between measles
virus infection and ileo-colonic lymphoid nodular hyperplasia
in affected children
This confirmed the presence of measles virus in the brain
tissue of a previously-healthy 21-month-old boy, 8.5 months
after he received MMR. The child had no history of exposure
to measles or if immune deficiency.
The nucleotide sequence in the nucleoprotein and fusion gene
regions was identical to that of the Moraten and Schwartz
vaccine strains. The fusion gene differed from known genotype
A wild-type viruses.
Dr. Singh explained that he had set out in his studies to
answer two questions:
Do autistic children have a hyperimmune response (or increase
of antibodies) for a specific virus?
Is there a relationship between virus antibodies and brain
autoantibodies in autism?
In his studies, he reported two important observations:
There was indeed a hyperimmune response to a virus, and it
was specifically for the measles virus, but not for the other
viruses tested (human herpes virus 6 (HHV-6), rubella virus
There was an association between measles virus antibodies
and myelin basic protein autoantibodies (i.e. The higher the
measles virus antibody level, the greater the chance of brain
He had previously already found that many autistic children
had antibodies to a specific protein of the MMR vaccine
These viral antibodies were also related to positive titers
of brain MBP autoantibodies.
This was probably the very first laboratory-based evidence
to link measles virus and/or MMR vaccine to autoimmunity in
children with autism.
These observations led Dr. Singh to speculate that autism
may be caused by a measles-induced, or MMR vaccine-induced,
autoimmune response, but further research was being delayed
by a lack of funding.
Dr. Singh reported his own anecdotal survey of apparently
vaccine-injured children with regressive autism. He found
that 93% of cases had autistic symptoms shortly after vaccinations.
Of these, 52% were post-MMR, 8% post MMR and DPT, and 33%
post-DPT. Just 7% were not linked by the parents to any vaccination.
He acknowledged that the survey was non-scientific.
Dr. Singh’s conclusion was that:
Rapidly-accumulating evidence strongly implicated autoimmunity
In many, this may have resulted from a vaccine injury
There was a possibility of an atypical measles infection in
autism, but the evidence also suggested an MMR vaccine infection
The Congressional Committee should explore the possibility
that the manufacturers had never properly evaluated the safety
of vaccines in the first place.
This paper reported a study using biopsy material from children
examined at the Royal Free in London. Dr. Wakefield at the
Royal Free had posed three questions to the O’Leary
(1) was measles virus present in gut biopsies of affected
(2) where was measles virus located in the gut biopsies of
the affected children?
(3) how much virus was present?
The O’Leary team used in-situ hybridisation (with/without
tyramide signal amplification), in-cell PCR, solution-phase
PCR, TaqMan quantitative PCR and DNA sequencing to determine
the answers to these questions.
Using TaqMan PCR the team was able to quantify the measles
virus copy number per 1,000 mucosal cells using gene dosage
correction formulations. The copy number of measles virus
in gut biopsies from children with autistic enterocolitis
was low, at approx. 30-50 measles virus genomes per 2,000
mucosal cells (inc. Gut, epithelial,lymphoid and dendritic
Confirmation of the presence of measles virus genomes was
achieved using positive and negative strand sequencing of
cDNA measles amplicons.
The results were that 24 out of 25 (96%) of the autistic children
were positive for measles virus, including 2 children from
the USA who were included in this analysis
In the controls, only 1 of the 15 children (6.6%) was positive
for measles virus.
The study therefore localised, quantified and sequenced measles
virus genomes in gut biopsies of children with autistic enterocolitis.
The study team then posed the question, "how did it get
Following reports that measles virus might be present in the
intestines of children with Crohn’s Disease, a new syndrome
was reported in children with autism who exhibited developmental
regression and gastrointestinal symptoms (autistic enterocolitis),
in some cases after MMR vaccine, was reported (see papers
by Wakefield et al). It was not known whether the virus, if
confirmed as present in these patients, derived from wild
strain or vaccine strain.
This study carried out the detection of measles genomic RNA
in peripheral mononuclear cells (PBMC) in 8 patients with
CD, 3 patients with UC and 9 patients with autistic enterocolitis.
As controls, the study used 8 cases of either healthy children
or children with SSPE, SLE or HIV-1. The results were:
1/8 patients with CD, 1/3 with UC and 3/9 with autism were
positive. Controls were all negative
The sequences from patients with CD shared the characteristics
with wild-strain virus.
Sequences from patients with UC and children with autism were
consistent with vaccine strain measles.
These results were consistent with the exposure history of
This study is obviously particularly important because it
points to infection with vaccine-strain measles virus.
This paper looked at organic anion-transporting polypeptides
(OATPs), a rapidly growing gene family of polyspecific membrane
transporters. The study looked at the human OATP. The results:
demonstrated that OATP-A can mediate transport of the analgesic
opioid peptides DPDPE and deltorphin II across the human BBB.
indicated that members of the Oatp/OATP gene family of membrane
transporters play an important role in carrier-mediated transport
of opioid peptides across the BBB and blood-cerebrospinal
fluid barrier of the mammalian brain.
These findings were not specifically linked to autism, but
help to support the opioid-peptide theory aspect of autism.
This study described endoscopic and pathological characteristics
in a group of children with developmental disorders that are
associated with behavioural regression and bowel symptoms,
and compares these with pediatric controls.
Ileocolonoscopy and biopsy were performed on 60 affected children
(median age 6 years, range 3-16, 53 male)
Developmental diagnosis were autism (50), Aspergers (5), disintegrative
disorder (2), attention deficit hyperactivity disorder/ADHD
(1), schizophrenia (1), dyslexia (1).
The results were that ileal-lymphoid nodular hyperplasia (ILNH)
was found in 54/58 affected children (93%) but only 5/35 (14.3%)
Colonic LNH was present in 18/60 (30%) affected children but
only 2/37 (5.4%) controls.
Reactive follicular hyperplasia was present in 46/52 (88.5%)
ileal biopsies from affected children and only 4/14 (29%)
UC controls, but not in IBD controls.
Active ileitis was present in 4/51 (8%) affected children
but not in controls.
Chronic colitis was identified in 53/60 (88%) affected children
compared with 1/22 (4.5%) controls and in 20/20 (100%) with
Scores of frequency and severity of inflammation were significantly
greater in both affected children and those with UC, compared
Although not a study (but see later), the statement by Professor
Spitzer deserves coverage. Professor Walter O. Spitzer, Emeritus
Professor of Epidemiology, McGill University, Montreal, stated
on December 6th 2000:
"The safety of MMR has been brought into question, both
in the United Kingdom and in California. It is not possible
to rule out the possibility that excessive rates of autism
occur among children immunised with MMR"
"The early epidemiological findings are worrisome. The
clinical and laboratory data strongly suggest the biological
plausibility of a link between MMR and autistic disorders"
(He) "......strongly endorses immunisation as a pillar
of public health strategy for most diseases. But one should
never surrender caution".
Following reported colitis with ileal lymphoid nodular hyperplasia
(LNH) in children with regressive autism, this study was undertaken
to characterise this lesion and determine whether LNH is specific
Ileocolonoscopy was performed in 21 consecutively evaluated
children with autistic spectrum disorders and bowel symptoms.
Blinded comparison was made with 8 children who had a histologically
normal ileum and colon, 10 developmentally normal children
with ileal LNH, 15 with Crohn’s disease and 14 with
Immunohistochemistry was performed for cell lineage and functional
markers, and histochemistry was performed for glycosaminoglycans
and basement membrane thickness.
In the results, histology demonstrated lymphocytic colitis
in the autistic children, less severe than classical inflammatory
bowel disease. However, basement membrane thickness and mucosal
cell density were significantly increased above those of all
other groups, including patients with inflammatory bowel disease.
CD8+ density and intraepithelial lymphocyte numbers were higher
than those in the Crohn’s disease, LNH and normal control
CD3 and plasma cell density and crypt proliferation were higher
than those in normal and LNH control groups.
Epithelial, but not lamina propria, glycosaminoglycans were
However, the epithelium was HLA-DR-, suggesting a predominantly
The interpretation of these results was that immunohistochemistry
confirmed a distinct lymphocytic colitis in autistic spectrum
disorders in which the epithelium appears particularly affected,
and that this was consistent with increasing evidence for
gut epithelial dysfunction in autism.
This study investigated the alleged causal association between
the onset of regression/autistic behaviour and infant immunisation,
viral infection and adverse reactions to common foods. In
the study, the authors hypothesised that children with regressive
autism may have an aberrant immune response against these
common, usually benign, factors. The study:
Determined innate and adaptive immune responses in children
with autism spectrum disorders (n = 35, age = 2-14 years,
median 6 years, 24 males, 9 females)
It found that the autistic children produced a higher TNF-?,
sTNFRII and IL-6, with a low dose of LPS, than controls. This
was due to a subset of patients who produced large amounts
of these cytokines
27/35 (77%) of the study cohort produced higher than the maximum
levels of TNF-?, sTNFRII and IL-6 and/or IL-1? observed in
The study also observed elevated serum levels of these cytokines
in 8 out of 18 autistic children
Results indicated a high frequency of excessive innate immune
responses in children with regressive autism
These results may partly explain the apparent association
between the onset of regression or autistic behaviour and
immunisation in these children
The study also assessed T1/T2 responses:
The ratio of IFN-?/IL-5 did not differ between autistic children
7 and 8 out of 35 autistic children produced significantly
high IL-12p40 with recall antigens IL-12 and IL-18 respectively
10 and 11 out of 35 subjects produced high amounts of IL-10
with PHA and tetanus respectively
12/35 subjects produced significantly low IL-10 with PHA as
compared to controls
The study team concluded that these results also indicated
aberrant production of regulatory cytokines for T cell responses
in subsets of autistic children.
The study determined innate and adaptive immune responses
in 71 children with developmental regression and autism spectrum
disorders (ASD), in 23 developmentally normal siblings and
in 17 controls. The study found:
A number of ASD children produced excessive proinflammatory
and regulatory cytokines associated with innate immunity compared
Some siblings of ASD patients showed abnormalities in production
of these cytokines
The findings may indicate the presence of aberrant immune
responses in ASD children with developmental regression at
The study team also observed:
Many parents report the onset of regressive autism following
immunisation and/or benign childhood infections, and aggravation
of symptoms following benign viral infection/immunisation.
Data supporting the role of infection/immunisation/dietary
protein Ag in ASD are scarce and inconclusive
Many ASD patients also suffer from recurrent/chronic ear infection,
sinusitis, viral infection and chronic diarrhoea/constipation
Jyonouchi et al commented: "Vaccination was developed
to provide protective immunity by stimulating the immune system
with killed or attenuated microbes. It is well known that
purified protein Ags are poor immunogens and will not induce
immunity if not given with adjuvenants. Adjuvenants augment
Ag-specific immune responses by activation of innate immunity,
by facilitating co-stimulatory molecule expression, Ag processing
and production of pro-inflammatory cytokines by APC".
Jyonouchi et al hypothesise that ASD patients with developmental
regression may have aberrant innate immune responses that
could result in increased risk for adverse reactions to benign
childhood infection, and even to immunisation. They also hypothesise
that aberrant innate immunity results in abnormal adaptive
immune response and intolerance to common environmental Ag
such as dietary proteins
The study report concluded: "Our results indicate for
the first time that a number of ASD children with developmental
regression are likely to demonstrate aberrant innate immune
responses that may also result in aberrant adaptive immune
This paper found that:
Just over 900 families whose children had had MMR were seeking
legal redress in the UK, and so reviewed a set of 493 of the
children’s National Health Service records. Some were
ineligible for various reasons, and the study therefore focussed
on 369 eligible cases.
Of these cases, there was classic ICD-10 autism in 259 cases,
atypical autism in 25, Aspergers in 30, specific language
impairment in 10, disorders of attention, motor control and
perception (non-ICD-10) in 2, and other childhood disintegrative
disorders in 2. There were no cases of Rett’s syndrome.
Of the cases of classical and atypical disorders, 112 (39%)
regressed, from "normal" function pre-MMR, to unequivocal
major deficits in function that fit conventional criteria.
A further 115 (40%) were "failure to develop" following
MMR immunisation. A further 30 (11%) manifested both regression
and failure to develop.
The median delay from first dose of MMR to diagnosis was 2.5
years, with the range being 0.5 years to 11.8 years. The interquartile
interval was 1.8 years to 4.2 years. Virtually none of the
cases would have been classifiable if followed for only six
weeks after MMR.
The project was acknowledged to be passive surveillance of
an unrepresentative group of children, almost certainly affected
by major underreporting.
The key finding is the delay between exposure to MMR and the
emergence of autistic symptoms or the delay to definitive
diagnosis of an autistic syndrome.
The median the authors report for delay to diagnosis is 2.5
years within an interquartile interval of 1.8 to 4.2 years.
That means that the assumptions about delay and the distribution
of delay in many published articles and safety assessments
This paper was dismissed in a Parliamentary Written Answer
by Lord Hunt, Government Health Spokesman in the UK House
of Lords on 3rd January 2002. Lord Hunt stated that ".......it
provides no scientific evidence to link MMR vaccine with autism,
(it is) strongly suggestive that MMR played no role",
and its findings "are also counter to the paper by Dr.
Andrew Wakefield and colleagues published in the Lancet in
1988, which reported rapid onset of behavioural symptoms,
median 6.3 days, after MMR".
In this paper, Dr. Aitken sets out several, possibly interacting,
biologically plausible mechanisms to link autism with immunisation:
An autoimmune reaction. This would be where the body’s
immune system raises antibodies to a vaccine virus, and those
antibodies go on to directly affect the functioning of the
central nervous system. A parallel might be drawn with disorders
known as PANDAS, where a movement disorder (Sydenham’s
chorea) occurs after a streptococcal infection, and can be
cured by removing the antibodies from the bloodstream. A number
of recent autism papers point to autoimmune problems
A gastrointestinal dysfunction, where interference with intestinal
function leads to alteration to endogenous opiate systems
or to food related opiate-like substances passing into the
bloodstream, reaching the brain and causing autistic-like
behaviour. The opioid hypothesis receives support from a range
of studies. Endoscopic research published to date demonstrates
abnormalities of both the oesophagus (Horvath et al) and the
intestine (Wakefield et al)
A direct viral infection of the central nervous system, although
evidence for this is more limited, being to date three deaths
from chronic measles infection of the nervous system (subacute
sclerosing panencephalitis, or SSPE), which have been reported
within the group of UK children whose cases are making their
way to the High Court
The authors noted that circulating immunoglobulin E (IgE)
is one of the characteristics of human allergic diseases including
allergic asthma. The authors had previously showed that infection
of human B cells with rhinovirus or measles virus could lead
to the initial steps of IgE class switching, and that, as
many viral vaccines are live viruses, they speculated that
live virus vaccines may also induce IgE class switching in
human B cells. To examine this, they selected the MMR vaccine.
In their study, they showed that infection of a human IgM+B
cell line with MMR resulted in the expression of germline
In addition, infection of freshly prepared human PBLs with
MMR vaccine resulted in the expression of mature IgE mRNA
The authors concluded that their data suggested that a potential
side effect of vaccination with live attenuated viruses -
in this case, specifically MMR - may be an increase in the
expression of immunoglobulin E
Dr. Buie reported that he had performed over 400 gastrointestinal
endoscopies with biopsies, and evaluation of digestive enzyme
function in children diagnosed with autism. The results of
his testing were reported to be similar to the observations
of Dr. Andrew Wakefield and colleagues at the Royal Free Hospital,
London. Buie had found:
The presence of chronic inflammation of the intestinal tract,
although the incidence was noted to be less frequent than
in the RFH group.
Biopsy results indicated the presence of chronic inflammation
of the digestive tracts, including esophagitis, gastritis
Lymphoid nodular hyperplasia had been found in 15 of 89 children
Results of enzyme testing had paralleled that of Dr. Karoly
Horvath and colleagues at the University of Maryland School
The autistic children examined showed disaccharide/glucoamylase
enzyme levels below normal
Some 55% of the children had lactase deficiencies (which break
down lactose in milk), as well as deficiencies of the enzyme
sucrase (responsible for digestion of table sugar).
Buie shared the opinion of a growing number of clinical researchers:
"These children are ill, in distress and pain, and not
just mentally, neurologically dysfunctional".
This study investigated the presence of persistent measles
virus in the intestinal tissue of 91 patients with new variant
inflammatory bowel disease, and examined a group of controls,
using molecular analysis.
Patient samples were provided by the Department of Gastroenterology,
Royal free Hospital, London. The 91 patients had a median
age of 7 years, age range 3-14, 77/91 were boys.
The 70 developmentally normal controls had age range 0-17
years, 47/70 were boys. These included 19 children with normal
ileal biopsies, 13 children with mild non-specific chronic
inflammatory changes, 3 children with ILNH investigated for
abdominal pain, 8 children with Crohn’s disease, one
child with ulcerative colitis, 26 children who had undergone
appendicectomy for abdominal pain including appendicitis.
Biopsies from the terminal ileum of affected children and
normal controls were examined. Measles virus fusion (F) and
Haemagglutinin (H) genes were detected by Taqman reverse transcription
polymerase chain reaction (RT-PCR) and the Nucleocapsid (N)
gene by RT in-situ PCR. Localisation of the mRNA signal was
performed using a specific follicular dendritic cell antibody.
Measles virus positive control material included 2 cases of
SSPE and MV-infected Vero cells. Negative control material
included uninfected Vero cells and human tissues, control
RNA extracted from Raji cells (Applied Biosystems, Foster
City, California) and normal peripheral blood mononuclear
The results of the study were:
75 of 91 patients with a histologically confirmed diagnosis
of ileal-lymphoid nodular hyperplasia and enterocolitis were
positive for measles virus in their intestinal tissue compared
with 5 of 70 controls.
70 of 91 affected children were positive for MV compared with
4 out of 70 controls as analysed by TaqMan RT-PCR
Measles virus was identified within the follicular dendritic
cells and some lymphocytes in foci of reactive follicular
hyperplasia. The copy number of measles virus ranged from
one to 300,000 copies/ng total RNA.
Of the paediatric controls, MV was not detected in normal
children or children with isolated ILNH. However, 4 out of
26 appendicectomy samples harboured the MV genome. The study
noted that the prevalence of MV in the general population
is unknown, and that this warrants further investigation.
The conclusion is that the data confirm an association between
the presence of measles virus and gut pathology in children
with developmental disorder
The study did not exclude the presence of alternative infections
to MV, and that viruses might exist elsewhere or exert a transient
effect. The study concluded that its findings raised many
questions - most importantly, does measles virus play an aetiological
role in intestinal inflammation in developmental disorder?
But the study raises for the first time an association between
MV infection and ileocolonic lymphonodular hyperplasia and
ileocolitis in children with developmental disorder.
Following their finding that many autistic children have autoantibodies
to brain myelin basic protein (MBP) and also elevated levels
of measles virus antibodies, Singh and Nelson conducted further
serological studies. These included measles virus (MV), mumps
virus (MuV), rubella virus (RV) cytomegalovirus (CMV), human
herpes virus-6 (HHV-6), MMR, DPT, diptheria-tetanus (DT),
and hepatitis B (Hep-B). These were then studied for correlations
with MBP autoantibodies.
Antibodies were assayed in the sera of autistic children (n
= 125) and in normal children (n = 92) by ELISA or immunoblotting
methods. The study findings were:
Autistic children have significantly higher than normal levels
of MV and MMR antibodies, compared with controls
The antibody levels of MuV, RV, CMV, HHV-6, DPT, DT and Hep-B
did not significantly differ between autistic and normal children
Immunoblotting analysis showed the presence of an unusual
MMR antibody in 60% (75 out of 125) of the autistic children,
but in none of the 92 controls
By using MMR blots and monoclonal antibodies, Singh and Nelson
found that the specific increase of MV antibodies or MMR antibodies
was related to measles hemagglutinin antigen (MV-HA), but
not to mumps or rubella viral proteins, of the MMR vaccine
In addition, over 90% of MMR antibody-positive autistic sera
were also positive for MBP autoantibodies, suggesting a causal
association between MMR and brain autoimmunity in autism
The authors concluded by suggesting that an "atypical"
measles infection, in the absence of a rash but with neurological
symptoms, might be etiologically linked to autoimmunity in
A US parents’ group, the Developmental Delay Registry,
has reported that of nearly 700 children aged between one
and twelve that had been surveyed in 1994:
those that had taken more than 20 cycles of antibiotics in
their lifetime were more than 50% more likely to suffer developmental
nearly 75% of the developmentally-delayed children had been
reported as developing normally in their first year of life
developmentally-delayed children were 37% more likely to have
had three or more ear infections than non-developmentally
developmentally-affected children were nearly four times as
likely to have had adverse reactions to immunisations
This states "In the course of its review the committee
encountered many gaps and limitations in knowledge.......(including)
inadequate understanding of biological mechanisms underlying
adverse events, insufficient information from case reports
and case series, inadequate size or length of follow-up of
many population-based epidemiologic studies".
The report received on this study, which is ongoing, states
Since the developing nervous system is uniquely sensitive
to damage following virus infection, postnatal CNS development
during the first year of life provides continued susceptibility
of the infant CNS to damage by viral infection after birth.
Administering neurovirulent vaccines to infants also places
the child’s CNS at increased risk for injury.
Wild type mumps virus, and some strains of mumps vaccine virus
(Urabe Am9, Leningrad 3) are amongst the most neurotropic
of the early childhood viruses, and new MMR combinations continue
to be proposed that include new strains of mumps vaccine virus.
It is important to develop valid molecular biological, inn-vitro
and in-vivo models to evaluate the pathogenesis of the neurotoxic
effects of vaccine viruses. Information obtained in these
studies about mumps virus vaccines will be likely to be useful
in generalising to other potentially neurovirulent vaccines,
Study progress on molecular markers of neurotoxicity:
We have identified vaccine virus related perturbations in
CNS gene expression by standard semiquantative RT-PCR and
by differential display techniques, including endogenous immune
mediators of the CNS.
We have recovered un-characterised gene products from new
genes that are altered by virus infection of the brain.
We have initiated RPA to compare changes in endogenous immune
mediators in the CNS in animals infected with low and high
neurovirulence strains of mumps virus
On animal models of CNS diseases following childhood virus
Viruses are known etiologic agents of autism (e.g. rubella).
Therefore concerns are raised regarding a possible relationship
between childhood vaccines and autism. Because no valid animal
model exists to study the pathogenesis of the neuroanatomical
and behavioural signs of autism, we developed a rat model
of autism using neonatal infection with neurotropic viruses.
We have characterised autistic-like changes in neuroanatomy,
neurological disease and behaviour in these rates. In addition,
we have identified regional and developmental changes in neurotransmitters,
including serotonin and norepinephrine.
A developmental study of damage to developing brains (e.g.
Cerebellum) in virus infected rats was performed, demonstrating
anatomical, behavioural and neurological consequences.
This study was conducted to clarify the validity of a causal
link between persistent mumps virus infection and inflammatory
The study used amplification of the mumps virus genome by
reverse transcription-polymerase chain reaction (RT-PCR).
The mumps virus genome was not detected in intestinal specimens
or peripheral blood lymphocytes.
It concluded that it could not find any evidence to support
a causal link with the mumps virus (note that this study did
not look at the measles virus component of MMR)
Spitzer’s testimony included the following:
(Commenting on safety studies) "I have not found scientifically
sound safety studies"
(On length of follow-up period) "I shall present new
data (see earlier) supporting the view that British evaluations
on safety of MMR in respect to autism invoked inappropriately
short lengths of follow-up".
(On single vaccines) "The intrusion of the authorities
in the legitimate freedom of choice of responsible parents
by proscribing monovalent products is self evident"
(On evidence for/against a link) "The data about biological
plausibility of an MMR/autism link has gradually become more
(On the view held by Fombonne, described earlier, that there
is no evidence of a rise in autism) "Declaring a non-epidemic
flies in the face of official statistics in government files
and several published papers.......Fombonne’s arguments
do not explain away such steep rises in occurrence of AuS
anywhere.......His letter gives inadequate attention to the
rate changes of subsets of AuS, such as regressive autism.
A worldwide epidemic of autism is in progress. That demands
serious scientifically admissable inquiries about possible
(On the Kaye et al study, reviewed earlier, hailed by the
UK Department of Health as evidence of no MMR/autism link)
"The Kaye-Jick study is the best published descriptive
epidemiological study to date demonstrating that an epidemic
of autism exists."
(On the UK Medicines Control Agency’s Yellow Card passive
reporting system for adverse events) "Passive surveillance,
pioneered by the British Yellow Card system and emulated world-wide,
was designed to raise warning flags on safety. The system
was never intended to be used the other way round, to confirm
(On Patja, Peltola et al, the Finnish study) "I find
no evidence that the study was set up to be sensitive to AuS,
nor that the surveyors or the reporters of events looked for
autism events at any time........A large scale study as was
done in Finland is not automatically well designed or adequately
reported because of its size.....There were no controls.....There
was no discussion about such uncontrolled surveys.....There
is no indication in the report about the length of follow-up.....There
is no information about the nature or content of briefings
to health care personnel before the study started, in relation
to the types of reactions and the inclusion of autism as a
reportable side effect.....Any assertion that the Patja-Peltola
paper "clears" MMR is unfounded."
(On Taylor, Miller et al, reviewed earlier) "The study
and its report are seriously, if not fatally, flawed.......Complete
ascertainment of all cases of autism in the eight districts
(of North London) is uncertain.......(there is) inadequate
classification of the various diagnoses within the autistic
spectrum.......There is a failure to correct for "catch-up"
components of the immunisation campaign (this is a reference
to 7.5m older children immunised in the UK in 1994).....An
incorrect analytic method was used. The case-series method
used by Taylor, Miller, applies primarily to acute events......One
does not expect autism to develop acutely.......(There was
a) failure to discriminate between types of MMR vaccine."
Spitzer concludes that the Taylor, Miller et al paper ".......which
is incorrectly interpreted as demonstrating safety, provides
much better evidence in the opposite direction, consistent
with MMR being associated with some AuS categories. Moreover,
an uncontrolled study is uninterpretable as the basis to demonstrate
a link between MMR and AuS, or to dismiss it aside, unless
the findings were dramatic and very clear."
The following are brief details about known UK studies investigating
an MMR/autism link, but which have yet to report:
This study, based at the Maudsley Hospital, Denmark Hill,
London (tel 0207 836 5454 email firstname.lastname@example.org) is
to assess if exposure to MMR immunisation is a risk factor
for autism, and to assess the exposure to viral infections,
both prenatally and postnatally.
The study will use UK GP data, hospital reports and a parents’
questionnaire. It will use over 400 cases of autism and four
times as many controls, selected from a GP database. It is
funded by the Medical Research Council (£351,000). No
date has been given for publication of the findings.
(Note: since this study commenced, Professor Fombonne has
also agreed to appear at the forthcoming UK High Court cases
as an expert witness on behalf of the manufacturers of MMR,
against the children. His current role within the study is
not known. It is also not known whether the control group
will be "unvaccinated with MMR", "unvaccinated
with MR", "unvaccinated with any measles-containing
vaccine", "unvaccinated with thiomersal-containing
vaccines" or "totally unvaccinated", or what
the vaccination status of the control group children’s
mothers will be. These may affect any study findings).
This study, based at the Behavioural Sciences Unit, Institute
of Child Health, Guilford Street, London, tel 0207 242 9789
email email@example.com) will look at a representative
population sample (but see caveats in previous section, final
paragraph) of 8 year olds who have received a diagnosis of
childhood autism or a related pervasive developmental disorder
The study will address the following questions:
Is the prevalence of autism in this population confirmed as
five times the established figure?
Alternatively, is the reported rate due to inaccurate over-diagnosis?
What is the rate of metabolic medical risk factors in autism?
To what extent are they specific to autism as opposed to other
neurodevelopmental and learning problems?
Do they distinguish between autism and related PDDs?
What evidence is there in this representative sample that
onset of symptoms is associated with MMR vaccination?
The study is funded by the Wellcome Trust (£461724).
This study, using the UK GP database, commenced in 2000, and
is expected to report in 2002. The study, to investigate the
causes of autism, including an assessment of the potential
role of MMR, will use case-control and case-series statistical
approaches. The electronic general practice records in the
database will be supplemented by record interviews of all
cases and questionnaires to both parents of affected children
and of controls.
A protocol paper of this study was reported in BMC Public
Health 2001, 1 (1): 2 in February 2001. The study is designed
If autistic children are more likely to have received MMR
vaccine prior to disease onset
To examine whether there is any association between clinical
onset of disease and the timing of MMR vaccination.
In July 2001, the research team, Hall, Smeeth and Fombonne,
wrote to the British Medical Journal, stating that "the
failure (of other studies) to find an association between
the time trends in vaccine coverage and the incidence of autism
codes in children’s electronic general practice records,
does not exclude a causal association".
(Note: Fombonne confirmed in summer 2001 that he was being
retained as an expert witness on behalf of the manufacturers
of MMR, and against the children, in the forthcoming UK High
The notification report of this current study (final reporting
date not known) stated that:
The prevalence of autism in Japan during the 1980s was 5-16
per 10,00, and was 21.1 in 1996. The apparent increase by
1996 was difficult to interpret, because it may have been
due to recent improved screening and other factors.
MMR was introduced in 1989 in Japan. The vaccination programme
was unsuccessful, on account of the higher incidence of associated
aseptic meningitis, and in 1993 the Ministry of Health &
Welfare discontinued MMR
During 1989-1992, 2.2 million doses of MMR and 3 million doses
of monovalent measles vaccine were distributed in Japan
The 1988-89 birth cohort received approximately 1.3 million
doses of MMR and 1.7 million doses of monovalent measles vaccine
It was noted that Kawashima et al had claimed that symptoms
developed soon after MMR in the majority of autistic cases
A case control study of the 1988-89 cohort would therefore
be of value for elucidating a possible relation between autism
This study is seeking explanations for the 273% increase in
cases of autism in California between 1987 and 1998. It will
examine a number of possibilities, including:
Whether there is a real underlying increase
Whether the criteria used in diagnosis has changed over time
Whether children have been misclassified in the past or at
the present time
Whether the number of families already with an autistic child,
and then later moving into California, has accounted for part
of the increase
If and how the characteristics of children with autism have
changed over time
The study will also ascertain the incidence amongst children
with autism of:
Specific medical or developmental problems such as retardation,
allergies, gastrointestinal disorders, and any pregnancy and
Regression, whether the children had a normal birth and developed
normally, then lost skills and regressed, as has been widely
reported by parents
Estimating how much regression now occurs, and whether this
has changed between the two age groups in the study
The study has enrolled 1,000 children, including 500 diagnosed
with autism and 500 with other developmental disabilities,
selected at random from the developmental services database.
One group of children with either of these characteristics
will be drawn from 15-17 year olds, and one group with either
disability from 5-7 year olds. The study will be completed
and report to the California State Legislature in early summer
If MMR "opens the gateway" to autism in genetically
or medically susceptible children, what does the actual damage
to the brain? A number of possibilities have been, and are
being, put forward. These may include thiomersal.
It is understood that thiomersal, a mercury-based preservative,
has been used in a number of UK and US vaccines over many
years. It is believed that it is not used in MMR itself, but
it may yet prove to have been used in the manufacturing process.
If this is the case, it is believed that no declaration has
to be made on the manufacturer’s information sheet,
as it is not an actual MMR constituent.
Worldwide, thiomersal has been used for about the past 60
years. Ethyl mercury constitutes about 49.6% of its weight,
and mediates the antimicrobial effects. Thiomersal has been
used to prevent bacterial contamination during the vaccine
manufacturing process, as well as in vials where repeated
puncture may allow contamination to occur.
It is believed that levels of thiomersal have been reduced
over the years in vaccines, and removed altogether in some
cases. In the US, in 2001, a free exchange system was instigated
by the manufacturers, to remove stocks.
In the UK, the Department of Health has refused to acknowledge
that there might be a problem with thiomersal, and no free
exchange system has been offered, or sought.
In the US, a September 2001 survey of 65,909 vaccines at provider
centres found that 5.5% still contained thiomersal. Some 36%
of these were DtaP-Hib for the fourth dose. A depot survey
of 837,174 vaccine doses found that 1% still contained thiomersal.
Of these, 80% were for DtaP.
In 1999, researchers calculated that a low-birthweight baby
could receive a cumulative dose of mercury (187ug) that would
have exceeded the safety recommendations of the US Environmental
In July 1999 the AAP and the PHS issued a joint statement
on thiomersal in vaccines, noting that the US Food & Drug
Administration Modernization Act of 1997 called for the FDA
to review and assess the risk of all mercury-containing food
The joint statement was generous in its self-reassurance:
"Thiomersal has been used as an additive......since the
"There is a significant safety margin incorporated into
all the acceptable mercury exposure limits"
"There are no data or evidence of any harm caused by
the level of exposure that some children may have encountered"
(Comment - but this may reflect lack of studies or lack of
monitoring, not lack of harm)
"Infants and children who have received thiomersal-containing
vaccines do not need to be tested for mercury exposure"
(Comment - as an example of complacency, this statement is
in a class of its own).
"The recognition that some children could be exposed
to a cumulative level of mercury over the first six months
of life that exceeds one of the federal guidelines on methyl
mercury now requires a weighing of two different types of
risk.....The large risks of not vaccinating children far outweigh
the unknown and probably much smaller risk, if any, of cumulative
exposure to thiomersal-containing vaccines" (Comment
- this is an tautological statement, and is revealing. What
the AAP/PHS are saying is, the risks from thiomersal are unknown,
are probably small, and are far outweighed by another risk
- which of course is an impossible deduction to draw if the
risks from thiomersal are unknown. One cannot say for certain
that A is larger than B if there is no way of determining
the size of B, or if the size of B is unknown because it has
been historically overlooked, and thus not measured).
"Nevertheless, because any potential risk is of concern,
the PHS, the AAP and the vaccine manufacturers agree that
thiomersal-containing vaccines should be removed as soon as
Key action agreed was:
A formal request to manufacturers for a clear commitment and
a plan to eliminate or reduce mercury content of vaccines
A review of data
Expedited FDA review of manufacturers’ supplements to
their product license applications, to eliminate or reduce
Studies to better-understand the risks and benefits of this
Vaccines in the UK that are believed to still contain, or
until recently contained, thiomersal are:
DTaP (Diptheria and Tetanus and acellular pertussis) made
by Lederle Laboratories
HIB (haemophilus influenza type B) made by Connaught Laboratories
DPT (Diptheria and tetanus and pertussis) made by Glaxo SmithKline
Energix-B (Hepatitis B) made by Glaxo SmithKline
HibTiter (Haemophilus influenza type B) made by Lederle
Fluvirin influenza virus vaccine made by Medeva Pharma
FluShield made by Wyeth-Ayerst
Menomune (Meningococcal polysaccharide vaccine) made by Connaught
Rabies vaccine made by Glaxo SmithKline
Recombivax (Hep B recombinant vaccine) made by Merck &
It is understood that the UK introduced an accelerated schedule
of DPT vaccination in the late 1980s/early 1990s, which would
have significantly increased the thiomersal intake of infants.
It is known that MMR does not contain thiomersal, but it is
thought that thiomersal may be used in its manufacturing process.
When the thiomersal issue was reviewed in the UK general practitioners’
magazine Pulse, the report concluded: "Another drawn-out
public debate might damage public confidence, and falling
vaccine uptake rates could cause the resurgence of preventable
diseases". This may be true, but this approach is also
a potential charter for complacency and secrecy. At what point
should safety concerns be publicly debated?
This meeting was convened by the US CDC to discuss the findings
of Dr. Verstraeten in relation to the positive statistical
association between thiomersal-containing vaccines and neurodevelopmental
disorders (thiomersal is a mercury-based preservative that
has been extensively used in the UK and US, and elsewhere).
The confidential version of the study reviewed at this meeting
clearly demonstrated that an exposure to more than 62.5 micrograms
of mercury within the first three months of life significantly
increased a child’s risk of developing autism. Specifically,
the study found a 2.48 times increased risk of autism.
In the US, courts of law have held that a relative increased
risk of 2.0 or higher is sufficient to substantiate that a
given exposure causes disease (in the case of Cook v. United
States, 545 F. Supp. 306, at 308, Northern District, California,
1982, the Court stated that "in a vaccine case, a relative
risk greater than 2.0 establishes that there is greater than
a 50% chance that the injury was caused by the vaccine").
The key findings of the Vaccine Safety Datalink analysis were
that there was a statistically significant association between:
A cumulative exposure to thiomersal-containing vaccines at
2 months of age and unspecified developmental delay
A cumulative exposure at three months of age and tics
A cumulative exposure at six months of age and attention deficit
A cumulative exposure at 1, 3 and 6 months of age and language
and speech delay
A cumulative exposure at 1, 3 and 6 months of age and neurodevelopmental
delays in general
The report noted that "the consultants were unanimous
in their opinion that further investigations should be pursued
with a degree of urgency".
These are some extracted comments from some of the key participants:
Dr. Weil: "There are just a host of neurodevelopmental
data that would suggest that we’ve got a serious problem"
Dr. Verstraeten: "We have found statistically significant
relationships between the exposures and outcomes for these
different exposures and outcomes. First, for two months of
age, an unspecified developmental delay which has its own
specific ICD9 code. Exposure at three months of age, Tics.
Exposure at six months of age, an attention deficit disorder.
Exposure at one, three and six months of age, the entire category
of neurodevelopmental delays, which includes all of these
plus a number of other disorders."
"Now for speech delays, which is the largest single disorder
in this category of neurologic delays. The results are suggestive
of a trend with a small dip. The overall test for trend is
highly statically significant above one".
"After excluding this speech group, the trend is also
apparent in this group (developmental delays, less those with
speech delays) and the test for trend is also significant
for this category excluding speech".
Dr. Davis: "In terms of a search for pre-disposing factors.....serious
and chronic otitis media by history, being mentioned by the
pediatrician or the specialist, was present 38% of the time".
(US parents’ note: doesn’t this sound familiar
to all of you parents with autistic children?)
Dr. Johnson: "This association leads me to favour a recommendation
that infants up to two years old not be immunised with thiomersal-containing
vaccines if suitable alternative preparations are available......there
are probably implications for this internationally".
Congress also ordered the Institute of Medicine (IoM) to investigate
the autism/MMR link, or identify another cause(s). The IoM
is a division of the National Academy of Sciences, whose members
serve as advisers to Congress. The IoM met in 2001, and also
looked at eight other vaccine-related safety concerns.
In March 2002, the lawyers Waters and Kraus, acting on behalf
of US children in the thiomersal/autism class action, stated
that their discovery process in their case of Counter v. Eli
Lilly (manufacturers of thiomersal) had demonstrated that
thiomersal was known by Lilly as early as April 1930 to be
dangerous. These included the following studies/warnings deposited
(1947) "It may be dangerous to inject a serum containing
merthiolate into a patient sensitive to merthiolate"
(1963) "It seems advisable to use a preservative other
than merthiolate for injections into merthiolate-sensitive
(1972) Merthiolate in vaccines caused six deaths - "The
symptoms and clinical course of the six patients suggest subacute
(1982) The (FDA) Panel concludes that thiomersal is not safe
for OTC topical use because of its potential for cell damage
if applied to broken skin, and its allergy potential".
In 1991, Lilly ceased the manufacture and sale of thiomersal,
but licensing agreements have revealed a continuing profits
stream until at least 2010.
In May 2001, the UK MCA instructed manufacturers to warn doctors
and patients of potential allergic reactions to vaccines containing
However, unlike the US, the UK has not moved to remove existing
stocks, which are being used up.
The magazine Pulse also reported that the UK Government planned
to reduce levels of thiomersal in infant vaccines, including
DTP, HiB and the pre-school DT booster.
It also reported that the UK Government was set to adopt guidance
from the European committee for proprietary medicinal products,
urging manufacturers to implement a stepwise reduction in
thiomersal levels in vaccines.
The UK DoH has traditionally failed to commission research
into the causes of autism. It seemingly prefers uncontroversial
research into detailed behavioural manifestations, or genetic
research that offers little insight into triggers. Also:
The UK Medicines Control Agency (MCA) has failed to properly
monitor adverse reactions to all vaccines, including MMR
The DoH repeatedly demonstrates an entrenched bias in favour
of maintaining public confidence in the vaccination programme,
and against investigating the causes of autism
The DoH repeatedly demonstrates dual standards of robustness
of evidence for/against an MMR/autism link, and repeatedly
shows this in its embracing of studies and findings that suit
The studies that the DoH quotes (Taylor, Miller, the Committee
on Safety of Medicines study, Gillberg, Peltola) are, when
critically examined, inconclusive or largely irrelevant in
terms of disproving any MMR/autism link.
The adverse reaction monitoring system has never been properly
reformed, because it would probably greatly increase adverse
reaction statistics, and this in turn would prompt political
pressure over possible vaccine damage, which in turn might
undermine public confidence
Autism has never been recognised as an adverse reaction, so
has not been reported as such (thereby potentially giving
false reassurance about vaccine safety records)
There also appears to be a very determined resistance on the
part of the UK DoH to understanding that slow descent into
autism takes place - it is not an acute adverse reaction,
like other alleged adverse drug reactions. The DoH is determined
to continue to ignore this, because acknowledging it would
invalidate many of the studies it quotes as "proof"
of MMR’s safety, eg the original safety trials, the
Peltola study, etc.
The greater their resistance, the stronger the suggestion
is that the DoH understands rather more about this syndrome
than it wishes to acknowledge publicly.
The (then) Medicines Division, predecessor of the MCA, was
admitted by its then management to have been in a disorganised
and dysfunctional state in 1988, the year that the MMR programme
commenced in the UK (see Draft Factual Account 17 of Evidence
to the BSE Inquiry, pp 31-33).
It had no effective method of finding files
It had severe staff shortages in key areas
Product licence renewals were handled purely administratively
without scientific input. MMR wasn’t a renewal, but
may have been treated as little more than one, as the single
vaccines were already licensed, and the long-term complications
and link with autism were not foreseen. It is therefore very
possible that MMR obtained its UK licence "on the nod",
with minimal investigation.
The Medicines Control Agency’ adverse reaction warning
system, known as the Yellow Card system, by their own admission
only picks up 10-15% of even serious adverse reactions (source:
Guidance on Interpretation of Yellow Card Data, MCA, 1997).
The system is thus officially acknowledged to be woefully
Yellow Card was unable to identify the potential problem over
autism because it must be shown that an adverse event occurs
more frequently in a vaccinated than unvaccinated population.
This is very difficult to do when almost all children are
vaccinated. (source: personal communication of the MCA of
Yellow Card depends on doctors, dentists, coroners and hospital
pharmacists to file reports (source: MCA). But these are unlikely
to be able to make the link between autism and MMR.
Adverse reaction reports are added to the ADROIT database,
introduced in 1991. However, the database can only deal with
the data it actually receives. If a syndrome is missed completely,
then there will be no data in the database.
Yellow Card is voluntary for health professionals, but compulsory
for pharmaceuticals manufacturers. But this depends on adverse
reactions being reported to manufacturers - again, unlikely.
Parents must also be able to make link between MMR/autism.
This was not possible pre-1998, as publicity had never been
given to a connection between vaccination and later degeneration
In any case, "it has been estimated.....that only 10-15%
of serious ADRs (adverse drug reactions) are reported"
(1997 Guidance Sheet issued by MCA), and "....it is accepted
that spontaneous reporting schemes have limitations"
(source: personal communication of the MCA of 29/3/99).
And more telling still, "Autism has been very rarely
reported as an adverse drug reaction.....These figures are
unsurprising since autism is not a recognised ADR to any particular
medicinal substance" (Source: personal communication
of the MCA of 29/3/99). Once again, this is a chicken-and-egg
And a potentially-significant admission, "Evidence from
the Yellow Card scheme is unlikely to resolve the issue as
to whether or not autism could be causally associated with
MMR vaccine" (Source: personal communication of the MCA
The MCA’s estimate of only 10-15% of ADRs being reported
may even itself be optimistic. The West Midlands Centre for
Adverse Drug Reactions Reporting did a survey and found a
rate of only 6.3% of all ADRs being reported.
All recent improvements to Yellow Card have been irrelevant
to autism detection (extension of the system to hospital pharmacists,
GP prescribing systems, community pharmacists, nurses)
A similar situation appears to apply in the USA - "On
the basis of Vaccine Adverse Event Reporting System alone,
we don’t have proof that vaccines are not contributing
to (vaccine-related problems)(source: Caveats to Interpretation
of VAERS Data, Centre for Biologics Evaluation & Research,
The whole monitoring system is therefore highly passive, and
potentially 100% irrelevant to detecting a link between immunisation
and autism, in the way it has operated.
On 22/1/01, the UK DoH launched a £3m publicity campaign
for MMR and rejected the Wakefield & Montgomery "Through
A Glass Darkly" MMR safety-test paper, without:
announcing any investigation into the affected children
offering any explanation as to why autism is rising so steeply
in UK and around the developed world (although the Medical
Research Council’s 2001 review was announced soon afterwards
- in the event, the latter proved to be yet another missed
The DoH also released the 15-page paper, "Combined MMR
Vaccines: Response of the Medicines Control Agency and DoH"
referred to above, to attempt to refute the Wakefield and
Montgomery paper. However, the DoH paper merely re-assembles
previous studies quoted by the Department, and adds nothing
new of note.
The Chairman of the Committee on Safety of Medicines, Professor
Alasdair Breckenridge, said "MMR vaccination is very
safe. There is no question-mark whatever over its licensing".
Professor Michael Langman, chairman of the JCVI, said "My
Committee has independently considered all the issues and
reached the same position as the Committee on Safety of Medicines".
The Chief Medical Officer, Professor Liam Donaldson, said
"We are very pleased to have this further confirmation
from the two independent expert committees".
Some parents feel that, in the absence of conclusive evidence,
either way, and taking all the surrounding factors into account,
the re-launch of MMR was a serious error, leaving the authorities
no escape should the test cases win in the High Court.
The Department of Health’s high-risk strategy would,
if this was the outcome, severely damage public confidence,
probably in all forms of immunisation. The repercussions for
the Department, and for child health generally, would be very
significant. The Department’s actions seem to have not
countenanced this potential future scenario.
The Medicines Control Agency has attempted to prevent single
vaccines from being administered, banning the importing of
further supplies and threatening any GP who administers single
vaccines with prosecution for breaching laws on importation,
sale or supply of unlicensed vaccines
In early 2002, press reports indicated a fresh major "push"
for MMR take-up:
North Cheshire Health Authority launched a major advertising
In both Scotland and Wales, there were press reports that
consideration was being given to making MMR compulsory for
all children starting at nursery schools. Any such move would
be highly controversial, and probably capable of successful
In February 2002, the UK Health Minister, England & Wales
Chief Medical Officer and Scottish Medical Officer announced
an intensification of the programme of persuasion that there
was no link between MMR and autism.
However, at the same time, there also appeared to be a shift
of policy in early 2002 as to the actual threat of a measles
In 2001, the Public Health Laboratory Service’s Communicable
Diseases Surveillance Centre stated: "We are below the
critical threshold at which point we run the risk of getting
a large number of cases. We will have to reverse that trend
because there is a significant chance we will get a major
measles outbreak or an epidemic".
Then, in January 2002, the Chief Medical Officer for England
and Wales stated: "There is no epidemic of measles and
there is no concern that there will be. There are not large
numbers of children dying of this disease".
The House of Commons Health Committee strongly urged in 1997
that a register be established of numbers of children with
autism. This was ignored by the Department of Health.
Evidence to the Health Committee was given on the MMR/autism
issue as part of its wide-ranging Inquiry into Adverse Outcomes
From Medical Care, June 1999. However, the Committee’s
report did not make any specific recommendation in relation
to the issue.
The Health Committee Chairman, David Hinchliffe MP, says he
still has questions over MMR issue, that there have been serious
concerns raised in his own constituency, and that he needed
to look for answers, and was to team up with members of Scottish
Health Committee to further investigate the MMR issue (report
in Daily Express 21/1/01)
An All Party Parliamentary Group on Autism has been formed
at Westminster. It is currently looking at diagnosis, education,
care and causation issues. The Chair is Dr. Stephen Ladyman
MP (Labour, Thanet South). Vice-Chairs are Lord Clement-Jones
(LibDem), Stephen Hesford MP (Labour), and Tim Loughton MP
(Conservative). The Treasurer is Brian Cotter MP (Labour).
Some 150 Members of Parliament are members of the APPGA.
The All-Party Group has called for clear progress on data-gathering
by Government. However, the APPGA has not implied that there
is any reason to question MMR’s safety at this stage.
The Health Committee of the Scottish Parliament appointed
a Reporter, Mary Scanlon MSP, in Autumn 2000, to examine the
issues surrounding the MMR/autism link and to report back
to the Committee. The Committee subsequently requested further
work, and set up an Expert Group to give advice. The Group
reports in February 2002. It is expected by the parents to
reject an MMR/autism link, as to do otherwise would prompt
a major controversy. Some elements of the expert committee
appear completely unpersuadable over MMR and autism. In February
2002 the expert committee was reported to be split.
In February 2002, the Scottish Chief Medical Officer stated
that calls to research the link between MMR and autism would
Susan Deacon MSP, the then Scottish Health Minister, has said
that the issue of single vaccines is a "reserved matter",
ie the power remains in Whitehall. However, Scottish MPs at
Westminster no longer cover health. So the Scottish democratic
representation is in Edinburgh, but the power is still in
London, and so this issue may yet cause a constitutional problem.
The Scottish National Party and Tommy Sheridan MSP of the
Scottish Socialist Party have both called for the re-introduction
of single (monvalent) vaccines in Scotland
In February 2002, Nick Harvey MP, Liberal Democrat health
spokesperson, stated in a personal communication that "We
do not doubt the integrity with which (Dr. Wakefield) approaches
his work, which is still at an interim stage. We note that
Dr. Wakefield’s opinions are not currently shared by
the vast majority (of the medical establishment). However,
there are also a number of parents who are convinced that
the MMR vaccine has been the cause of their children developing
autism......Liberal Democrats......respect the right of parents
to choose to have the vaccinations administered separately,
this being preferable to children slipping through the net
However, the current Liberal Democrat Health Spokesman in
the UK House of Commons, Dr. Evan Harris, has repeatedly insisted
that MMR is safe, and has opposed calls for the re-introduction
of single vaccines.
The Conservative health spokesman, Dr. Liam Fox, has expressed
his support for MMR but has also expressed his view that the
provision of single vaccines would be preferable to children
being unimmunised at all, and would reflect the wishes of
parents for being offered a choice. In February 2002, this
became Conservative policy. The usual cross-party consensus
on vaccination policy has therefore broken down. This is without
A Conservative MP, Ms. Julie Kirkbride, has vigorously promoted
a Private Member’s Bill to bring about the re-introduction
of single vaccines. In February 2002, her call for the re-introduction
of single vaccines to give parental choice was publicly endorsed
by another Conservative MP, George Osborne.
In April 2000, Rep. Dan Burton, Chairman of the US House of
Representatives Committee on Government Reform, initiated
a series of hearings into the relationship between vaccination
and autism. Some of the submissions of evidence to the hearings
have been described in earlier sections.
In a statement on 15th June 2000, Burton criticised the Food
& Drug Administration’s Vaccines and Related Biological
Products Advisory Committee (VRBPAC) and the Centers for Disease
Control and Prevention’s Advisory Committee on Immunisation
Members of these committees, including chairmen, were found
to own stocks/shares in the companies that make the vaccines.
Individuals held patents for vaccines under consideration
The CDC granted conflict-of-interest waivers, a year at a
time, to its committee members
The CDC’s committee had no public members, and the FDA’s
committee had only one.
Burton concluded that "conflict of interest rules employed
by the Food and Drug Administration and the Centre for Disease
Control have been weak, enforcement has been lax, and committee
members with substantial ties to pharmaceutical companies
have been given waivers to participate in committee meetings".
The Committee on Government Reform found that the majority
of members of both the FDA and CDC committees had financial
ties to vaccine manufacturers or held patents on vaccines
The Committee Chairman, Rep. Dan Burton, said: "For the
public to have confidence in the decisions made by their government,
they must be assured that those decisions are not being affected
by conflict of interest. It has become clear over the course
of this investigation that the FDA’s Vaccines &
Related Biological Products Advisory Committee and the CDC’s
Advisory Committee on Immunisation Practices are dominated
by individuals with close working relationships with the vaccine
producers. This was never the intent of the Federal Advisory
Committee Act, which requires that a diversity of views be
represented on advisory committees" (my emphasis).
Parents giving evidence to the Committee on Government Reform
told repeatedly-similar stories of how their child had developed
normally, then received triple vaccines (MMR or DPT) and had
gradually become autistic.
A number of researchers in the field gave detailed evidence
on autism incidence and its steep climb to near-epidemic (for
a supposedly-rare condition) proportions
The cause of autism could not be explained away by genetics,
because genetics do not cause epidemics within only two decades
- the two decades that multiple vaccines have become standard
The US agencies defending MMR made their own presentations.
Some acknowledged financial links with vaccine manufacturers.
Others said they were "looking into" the MMR/autism
connection, but their stance suggested an entrenched hostility
to the concept of any link.
Overall, these agency representatives displayed indifference
and an unconvincing grasp of the facts. (Note: an entire industry
of "looking into it" has developed, both in the
US and the UK. In the US, this has reported to have consumed
$100m in two decades of lack of progress).
Controversial areas of research are being avoided, in favour
of more abstract genetic-background research. Key leads are
not followed up, so progress is understandably very poor.
At every turn, the researchers try to prove that MMR and DPT
are not involved. Obvious approaches, such as comparing significant-sized
cohorts of triple-vaccine-immunised and unimmunised children
- the most promising line of any scientific exploration -
are not taken.
Further hearings by the Government Reform Committee are planned.
Other relevant points:
In February 2002, Rep. David Weldon, a Florida physician and
member of the US House of Representatives, urged the American
Academy of Pediatrics to fully inform parents of their choice
in having MMR separated-out and administered at different
times. He stated that he was "very disturbed" by
the recent Uhlmann, Wakefield, O’Leary et al paper,
and that there was an "epidemic" of autism among
There has been strong criticism of the US regulatory mechanisms
for drugs and adverse drug reactions by the Committee on Government
Reform, and by others. The consumer group Public Citizen found
that only 13% of 88 follow-up studies required as a condition
for the licensing of drugs launched in the early 1990s were
actually completed. Public Citizen’s Health Research
Group said that the neglect of follow-up studies could mean
that side effects are going undetected.
A "USA Today" investigation of FDA advisory committees
between 1/1/98 and 30/6/00 found that at 55% of meetings,
half or more of the FDA advisors present had conflicts of
interest. At some meetings, over 90% of advisors present had
conflicts of interest.
Federal law generally prohibits the FDA from using experts
with financial conflicts of interest, but this has been side-stepped
by using waivers. The FDA issued more than 800 waivers between
1998 and late 2000. Some 300 advisors serve on 18 advisory
The above puts "under one roof" a considerable amount
of information on the MMR/autism issue, though it cannot possibly
be an exhaustive coverage, given the many issue involved and
the ongoing scientific debate. However, it demonstrates that:
There is considerable evidence of (in relative terms) an autism
epidemic, with large increases being reported, though being
dismissed by some observers. It also begs the question "how
large an increase in the numbers is needed before the authorities
accept there really is an increase?". But common sense
suggests a sharp rise.
There are many studies that seek to deny an MMR/autism link,
but it is possible to demonstrate that each is flawed in several
ways. These studies are also statistical/epidemiological-type
studies - not studies of the actual children involved. They
are also based upon small (for statistical-type studies) samples.
There are strong grounds for believing that the safety studies
of MMR were cursory, that the potential for damage was not
recognised, and that subsequent safety follow-up has been
There are many papers that point - some of them powerfully
- to an MMR/autism link. Some of these studies involve analysis
of samples of the actual children involved
Putting the above conclusions together, there appears to be
strong grounds for believing that children have been damaged,
and are still being damaged, by MMR. No alternative credible
explanation has been put forward for these children’s
condition. The explanation that their degeneration into autism
is biologically linked to MMR is also supported by the accounts
of the parents of the actual children.
Some outstanding questions, which the media may find useful
to bear in mind, are offered here...
(Q1) Does the DoH/Minister accept that parents’ reports
are to a consistent pattern?
(Q2) Why was autism rare a couple of decades ago but now much
(Q3) Why do reviews such as the 2001 review by the Medical
Research Council stretch out so hard to reach the comforting
explanation that it’s mainly a matter of better recognition
and improved diagnosis, when they have no scientific justification
or hard data for doing so?
(Q4) Just how large an increase in autism numbers is required
for it to be recognised as a real increase?
(Q5) why were most autism cases prior to the late 1980s, the
time of introduction of MMR, of children who failed to develop
in very early infancy, whereas very many cases nowadays -
paradoxically, when there is now much better recognition of
the condition (i.e. when it is much less likely to be missed
in early infancy) are now of acquired autism, after a normal
(Q6) does the DoH etc accept that the alleged new syndrome
involves slow degeneration over many weeks/many months/several
years, rather than an acute event within a few days, or at
most three weeks, of MMR vaccination?
(Q7) does the DoH accept that many autistic children have
extreme multiple food allergies, and that the onset of these
approximately coincided with the onset of their autism?
(Q8) Ditto question for bowel conditions.
(Q9) related question: does the DoH etc accept that simultaneous
or sequential onset of gut/bowel/autism problems could be
(Q10) is the DoH monitoring England/Wales autism numbers centrally?
(they are not!)
(Q11) are UK health authorities/Boards monitoring autism locally,
to a consistent degree? (they are not!)
(Q12) is the UK DoH aware of the well-documented huge increase
in autistic pupils in the US, 1993-2001 up from 12,222 to
78,717? (the UK DoH likes to quote that "MMR is safely
used in the US")
(Q13) what research has the DoH etc commissioned into possible
causes (as opposed to the genetic susceptibility aspect) of
autism. What is its £ value over how many years?
(Q14) What new research into causes has been recently commissioned?
(Q15) has the DoH (or anyone in the UK Government?) made any
estimate of the national financial costs of autism? (health,
education, social services care, etc multiplied by numbers
of cases multiplied by years of life expectancy)?
(Q16) was the UK Medicines Division in complete disarray and
chronically understaffed in 1988, the year MMR was introduced?
(it was - see BSE Inquiry evidence, Draft Factual Account
17, pp 31-33)
(Q17) did the Taylor, Miller et al North London study find
that autism was increasing?
(Q18) did the 2001 Medical Research Council review into autism
find that autism was running at a rate of 1/166?
(Q19) is it admitted that the Patja, Peltola et al (Finland)
study only followed up 173 of the 1.8m children/troops/other
(Q20) is it true that all these 173 cases were only those
with acute gastrointestinal or other problems (vomiting etc),
not slow long-term degenerative problems?
(Q21) was the study designed to look at autism? (Peltola has
publicly admitted it wasn’t), and would local paediatricians
in Finland have connected autism with vaccination at all at
that time? (they certainly wouldn’t, no-one had ever
suggested it then, 15 years ago)
(Q22) does the DoH etc concede that long-term (six months
plus) follow-up was not undertaken of a sufficiently convincingly
large sample (10,000-plus) children prior to MMR licensing,
and that the UK was in effect trusting to safety because MMR
was already widely used elsewhere, eg the US? (they’ll
never admit this, but keep trying)
(Q23) did the Medicines Division license MMR on the basis
that it was only the amalgamation of three existing licensed
vaccines, without considering that their combination could
have a synergistic effect?
(Q24) is autism now recognised and recorded even as a potential
adverse reaction, nowadays, by the Medicines Control Agency
as part of the Yellow Card warning scheme? (very important
(Q25) are UK doctors now specifically advised by the DoH to
look out for degeneration as a potential adverse consequence
of immunisation? (Lord Hunt recently confirmed in a Parliamentary
Written Answer to Lord Clement-Jones that they were not).
(Q26) Has there been any further recent guidance on this,
in the light of the study by Spitzer, Aitken et al? (there
(Q27) why has the UK Medicines Control Agency not instructed
health authorities to replace existing stocks of thiomersal-containing
vaccines with non-thiomersal containing vaccines, when there
is concern over adverse reactions to thiomersal, and when
the manufacturers are operating a free-exchange scheme in
(Q28) how will the Department of Health/whoever rebuild confidence
in the immunisation programme if the children win in the forthcoming
UK High Court cases?
(Q29) will the Chief Medical Officer, Minister for Public
Health (whoever), resign if MMR children win in the High Court?
(Q30) who else will be expected to resign?
David Thrower, UK tel. 01925-264156, non-UK 44 1925 264156
18th March 2002