UPDATED [July 2004] MMR and Acquired Autism (Autistic Enterocolitis) - A Briefing Note by David Thrower

MMR and Late-Onset Autism -(Autistic Enterocolitis) - A Briefing Note by David Thrower

March 2001


Part A - Introduction
1. Summary
2. Late-onset Autism/Autistic Enterocolitis
3. The New Syndrome

Part B - The Parents, The Children, The Costs
4. UK Parents Taking Legal Action
5. The Parents’ Reports
6. Financial Costs

Part C - UK Autism Numbers
7. Failure to Monitor UK Increases
8. "Now Almost Everyone Knows Someone......"
9. University of Cambridge Research
10. University of Sunderland Research
11. National Autistic Society Estimates
12. UK Department of Health Views
13. Fombonne Paper

Part D - The USA
14. Autism In The USA
15. California

Part E - Inconclusive "Evidence" Against There Being An MMR/Autism Link
16. Taylor, Miller North London study
17. UK Committee on Safety of Medicines study
18. Gillberg study
19. Patja (Peltola) study
20. Kaye et al paper
21. Stokes et al paper
22. Medical Research Council Ad-Hoc Review, 1998
23. Medical Research Council Sub-Committee Report, 2000

Part F - Evidence To Suggest That There Is A Link/Other Papers
24. Weibel et al paper
25. Delgiudice-Asch et al paper
26. Fudenberg paper
27. Singh paper
28. Further Singh paper
29. Singh, Warren et al paper
30. Weizman et al paper
31. Gupta et al paper
32. Oleske and Zecca paper
33. Binstock paper
34. Griffin paper
35. Auwaerter and Griffin paper
36. Martinez paper
37. Wakefield et al "Early Report" paper,
38. Sabra, Bellanti and Colon letter
39. Cook et al paper
40. Warren paper
41. Warren and Singh studies
42. Kulman paper
43. US Developmental Delay Registry
44. Other Researchers
45. Professor Spitzer statement
46. Wakefield & Montgomery "Through A Glass Darkly" MMR safety-studies paper
47. Wakefield/Watson/Shattock Rebuttals
48. UK Department of Health Rebuttals
49. UK Department of Health Re-Launch of MMR

Part G - Flawed UK Regulatory and Monitoring Systems
50. Fighting Measles, Missing Vaccine Damage?
51. How the Medicines Control Agency Missed the Syndrome?
52. Subculture of the Regulatory Establishment
53. Independence of the Committee on Safety of Medicines?
54. Independence of the Joint Committee on Vaccination and Immunisation?
55. Lack of Public Scrutiny of CSM & JCVI
56. Monitoring of Medicines Control Agency and Public Health Laboratory Service
57. Monitoring of Department of Health

Part H - Various Experiences Elsewhere
58. Measles Outbreak, Republic of Ireland
59. MMR in Japan
60. Autism in Finland

Part J - Political Initiatives
61. UK All Party Parliamentary Group on Autism
62. Scottish Parliament
63. UK Liberal Democrats
64. UK Conservatives
65. US House of Representatives

Part K - Recent & Coming Events
66. Recent and Coming Events, UK
67. Ireland
68. USA
69. Just One More Question, Minister.........

David Thrower, 01925-264156, email David@ThrowerWarrington.freeserve.co.uk

Part A - Introduction

1. Summary

This note sets out, in some detail, the concerns of parents whose children have become autistic after MMR or measles-containing vaccines.

2. What Is Late-Onset Autism/Autistic Enterocolitis?

3. The New Syndrome

This is a summary of the new syndrome of autistic enterocolitis:

Part B - The Parents & The Children

4. The UK Families Taking Legal Action

5. The Parents Have Seen What They’ve Seen

6. The Financial Costs - Autism Is Costing Billions

Quite apart from the immense social costs of autism, there are the huge financial costs. Autism effects every UK taxpayer. The costs comprise:

In June 2000 a study for the Mental Health Foundation found that the annual costs of autistic disorder in the UK were at least 1 billion, and that individual lifetime costs per child affected could run to 2.94 million.

Part C - Autism Numbers

7. Failure To Monitor Increases In Autism Numbers

8. "Now Almost Everyone Knows Someone Who’s Autistic"

Evidence of dramatic rates/ increases

9. Cambridge University Research

On 18/2/01, the UK "Sunday Telegraph" reported on research undertaken by Dr. Fiona Scott at the Autism Research Centre at the University of Cambridge. The research, undertaken across schools in Cambridgeshire, found that:

10. University of Sunderland Research

A study to be published in April 2001 will show a tenfold increase in diagnosis of autism, during the years 1989-93.

11. National Autistic Society Estimates

The NAS issued a factsheet in early 1997 which gave the following prevalence rates:

The above implies a very high level of autism in the UK, and the previously-described studies seem to bear this out.

12. Is Autism Increasing? - The Department of Health’s View

13. The Fombonne Paper, January 2001

Part D - The USA

14. Autism In The USA

15. California

Part E - Inconclusive "Evidence" Against There Being A Link

16. The Taylor, Miller et al North London Study, June 1999

The 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).

But these bodies are closely intertwined, and have staked everything on a tiny handful of very small studies that have completely failed to get at the truth (this failure is obvious to anyone reading these studies, but most media and the medical establishment has probably relied on prepared "summaries" and press releases).

First, the Taylor, Miller et al study, 6/99:

17. Committee On Safety of Medicines Study, June 1999

In the words of the study report......

Study run as knockout competition: each case had to pass 4 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 effect?

18. Gillberg Study, Sweden

19. Patja et al Study (Peltola Study), Finland, December 2000

Other awkward facts re Peltola:

UK DoH also said in correspondence, speaking of 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...."

20. The Kaye, Melero-Montes and Jick Paper, BMJ, February 2001

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, when MMR’s coverage reached near-saturation almost immediately after introduction.

21. The Stokes et al Paper, Trivalent Combined Measles Mumps Rubella Vaccine, Journal of the American Medical Association, 4th October 1971

This paper, by Stokes, Weibel, Villarejos, Jorge, Arguedas, Buynak and Hilleman, has assumed more importance recently, see later Wakefield/Watson/Shattock debate section.

22. Ad-Hoc Medical Research Council "Committee of 37 Independent Experts"

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

23. The Medical Research Council’s Report ("Report of the Strategy Development Group Sub-Group on Research into Inflammatory Bowel Disorders and Autism", March 2000

This was yet another review group which, upon failing to prove that there was a link, then drew the illogical and unproven conclusion that MMR therefore was safe.

For autism, its recommendations included:

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).


24. Paper By Weibel, Caserta, Benor and Evans, "Acute Encephalopathy Followed By Permanent Brain Injury Or Death Associated With Further Attenuated Measles Vaccines: A Review of Claims Submitted to the National Vaccine Injury Compensation Program", Pediatrics, Vol 101 No. 3 March 1998.

25. US paper, by Drs. Delgiudice-Asch (clinical instructor in psychiatry, Mount Sinai School of Medicine) and Hollander (Seaver Autism Research Centre)

This includes:

26. Paper, Dialysable Lymphocyte Extract In Infantile Onset Autism: A Pilot Study, has been published (journal not identified) by Dr. H. H. Fudenburg of the NeuroImmuno-Therapeutics Research Foundation, Spartanburg, South Carolina.

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:

Fudenberg states that:

27. Unpublished paper by Dr. Vijendra Singh at the College of Pharmacy, University of Michigan, Ann Arbor, jointly with the late Professor Reed Warren, Professor of Biology at the Centre for Persons with Disabilities, Utah State University in Logan and Adjunct Professor of Psychiatry at the University of Utah, and also Dennis Odell

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:

The features above included genetic predisposition, gender imbalance (four or five times higher frequency in boys than girls), major histocompatibility association, and immune activation.

28. Further unpublished US paper, from Dr. Vijendra Singh

This suggests that:

29. Paper by Singh, Warren, Odell, Warren and Cole, published in Brain Behaviour 1993 March 7(1) 97-103

This investigated the possible pathological relationship between autoimmunity and autism, reported that:

30. Paper by Weizman, Weizman, Szekely, Livni and Wijsenbeek, published in the American Journal of Psychiatry 1982 Nov 139 (11) 1462-5

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 found:

31. Paper by Drs. Gupta, Aggarwal and Heads, titled Dysregulated Immune System in Children with Autism - Beneficial Effects of Intravenous Immune Globulin on Autistic Characteristics, published in the Journal of Autism and Developmental Disorders, vol. 26 no. 4 1996

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

32. Unpublished US paper, by Dr. Oleske and Assistant Professor Zecca, New Jersey Medical School

This found that:

33. US paper by Teresa Binstock, Researcher in Developmental and Behavioural Neuroanatomy, IMI, Denver

This found that

34. Paper by Diane E. Griffin, D. E. Hussy et al, John Hopkins University, US, has established (source: Journal of Infectious Diseases, 173 (6), 1320-26, June 1996)

This found that:

These researchers found that:

35. Paper by P. G. Auwaerter and Diane Griffin, (source: Clinical Immunolgy and Immunopathology, 79(2): 163-70, May 1996):

This found that:

36. Paper by Martinez et al, (source: Proceedings of the National Academy of Sciences, 94.8726-31 1997):

This found that:

37. Early Report by Dr. Andrew Wakefield and team, Inflammatory Bowel Disease Study Group at the Royal Free Hospital, London

Dr. Wakefield suggested in early 1998 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, his initial findings suggested that his hypothesis was plausible. The Royal Free Hospital study found:

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 evidence to contradict this hypothesis has been offered to date by the UK Department of Health, 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 source.

38. Letter published in The Lancet, Vol. 352, July 18th 1998, from Drs. Sabra, Bellanti and Colon of the International Centre for Interdisciplinary Studies of Immunology and the Department of Paediatrics, Georgetown University Medical Centre, Washington DC

This stated that:

39. Dr. Edwin Cook, Director of the Laboratory of Developmental Neuroscience, university of Chicago, in a joint paper with Courchesne, Lord, Cox, Yan, Lincoln Haas, Courchesne and Leventhal, published in the May 1996 edition of Molecular Psychiatry

This noted that:

40. The late Dr. Reed Warren, formerly Professor of Biology at Utah State University in Logan, set out a pathogen-autoimmune hypothesis for autism:

Dr. Warren outlined the possibility of several key factors, which included:

41. Warren and Singh studies

In his own studies, jointly with Singh et al, published in the journal Immunogenetics 36:203-207 of 1992, he noted that:

He 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 would occur. He also noted that 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. He also noted that 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 well-established. He further noted the link between genetic background and frequency of infections:

42. Paper by Kulman, Neri, Rovelli, Roselli, Lissoni and Bertolini, Divisione di Neuropsichiatria Infantile, Ospedale S. Gerardo, Monza, Italy

This examined the role of the pineal hormone melatonin (MLT) in the pathogenesis of autism. The study included 14 children affected by autism, median age seven years, mostly suffering sleep disorders, and found that:

43. A USA parents’ group, the Developmental Delay Registry, has reported that of nearly 700 children aged between one and twelve that had been surveyed in 1994:

44. Other Researchers Who Believe Link Possible

45. Statement by Professor Walter O. Spitzer

Although not a study, the statement by Professor Spitzer deserves a high profile. Professor Walter O. Spitzer, Emeritus Professor of Epidemiology, McGill University, Montreal, stated on December 6th 2000:

46. Wakefield & Montgomery "Through A Glass Darkly" Paper (Look Back At MMR Safety Trials), Journal of Adverse Drug Reactions, 2000 19(4), 265-283)

Wakefield & Montgomery reviewed 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.

Peer review comments on Wakefield & Montgomery paper very powerful. Peer reviewers included Dr Peter Fletcher, former Principal Medical Officer in Medicines Division (now MCA), who was medical assessor to Committee on Safety of Medicines. His comments:

Wakefield paper is actually argument for vaccination - but not using triple measles-containing vaccines. Wakefield not anti vaccination per se. Duty is to patient. He is investigating children brought to him, not campaigning against DoH for its own sake. He is simply relating what he is finding.

Other background points relevant to paper:

47. The Wakefield/Watson/Shattock Rebuttals - "Anything You Can Rebut, I Can Rebut Better"

Through A Glass Darkly safety paper by Wakefield and Montgomery has been 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 Sunderland University Autism Research Unit (tel 0191 515 2000). The only aspects that cannot be bottomed-out by Shattock are where the studies themselves have not been published.

Other "facts" quoted by Watson in "Aventis Pasteur MSD - Vaccines For Life" paper:

48. UK Department of Health Repudiation of Wakefield & Montgomery "Through A Glass Darkly" Paper

The UK DoH’s response was summarised in its press release of 21st January 2001. The main points are set out below, with the DoH in italics, and with my own responses following.

In short, the DoH’s rebuttal was a "non-denial denial". It 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 DoH was unable to refute this detail - indeed, it largely avoided addressing it at all.

49. Department of Health Re-Launch of MMR, 22/1/01

On 22/1/01, DoH launched 3m publicity campaign for MMR and rejected Wakefield "Through A Glass Darkly" MMR safety-test paper, without:

PART G - Flawed Regulatory & Monitoring Systems

50. Fighting Measles, Missing Vaccine Damage

51. Has The Medicines Control Agency Missed The Syndrome?

52. The Subculture of the Regulatory Establishment

All this makes more sense if you study the subculture:

53. Independence of the Committee On Safety Of Medicines?

Specific members of CSM linked with MMR manufacturers are:

(total 16 members)

54. Independence of the Joint Committee on Vaccination and Immunisation?

A Parliamentary Written Question by Mrs. Ann Winterton MP in May 1999 confirmed the following declared interests within the JCVI membership (NB - the PWQ related only to a limited range of pharmaceuticals companies, so the full list will be greater than this):

(total 6 members)

55. Lack of Public Scrutiny of the Committee on Safety of Medicines, the Joint Committee on Vaccination and Immunisation, and the Standing Medical Advisory Committee

In its Memorandum 9 of 24th November 1999 to the Select Committee of the House of Commons, the UK Department of Health sets out how its Non-Departmental Public Bodies (NDPBs) have provided information on openness of government. This was a response to the consultation document "Quangos - Opening The Doors", about improving the scrutiny of Quangos (a "Quango" is a quasi-autonomous non-governmental organisation, such as the Committee on Safety of Medicines or the Medicines Control Agency).

1 Required to publish an annual report
2 Required to publish an annual account
3 Subject to a full audit by the National Audit Office or equivalent
4 Comes under scrutiny of the Parliamentary Ombudsman/other ombudsman
5 Has its own complaints procedure
6 Has to observe code of practice on access to Government information
7 Allows public to inspect register of (organisation’s) member’s interests
8 Has public right to attend Board or Committee meetings
9 Is obliged to release reports of above meetings
10 Has public right to inspect agendas of above meetings
11 Has public right to inspect minutes of above meetings
12 Is required to hold public meetings
13 Has Register of Members’ Interests
14 Maintains internet site
15 Is considering developing internet site
16 Has been recently (in last year) subject to "Quinquennial Review"

It is not clear what role the Standing Medical Advisory Committee (SMAC) has in relation to MMR. Its Register of Members’ Interests is published on the Internet, but does not give details as to the pharmaceuticals companies involved, annotating each member as having "consultancies, directorships and similar positions", "fee-paid work", shareholdings, "fellowships", "industrial support" and "other".

The failure to specify what these actual links are, how many companies are involved or the value of significant financial interests is wholly unsatisfactory.

56. Monitoring Declared Conflicts of Interests Within Medicines Control Agency and the Public Health Laboratory Service

These two bodies are executive non-departmental public bodies (NDPBs). Conflicts of interest are handled by the Guidance on Codes of Practice for Board Members of Public Bodies. This states (with my own comments following):

A Parliamentary Written Question by Mrs. Ann Winterton MP in May 1999 confirmed that, of the PHLS:

In February 2001, the Committee on Standards in Public Life confirmed that the Guidance on Codes of Practice for Board members of Non-Departmental Public Bodies is published by the Central Secretariat in the Cabinet Office. Anyone researching this further should approach that office.

The Committee also confirmed that:

The Office of the Commissioner for Public Appointments (tel 020 7276 2625) confirmed the following in February 2001:

Again, there seems to be no outside scrutiny whatever of these measures in practice.

57. Conflicts of Interest/Declared Personal Interests Within UK Department of Health

Is the management of the key sections of the Department of Health truly 100% independent over the MMR/autism issue? There is no evidence whatever to suggest that pecuniary or other non-legitimate interests or considerations have in practice influenced civil servants’ judgement, but the question is a legitimate one purely in principle, and therefore the monitoring of such potential conflicts of interest is briefly reviewed here, for completeness.

The background to this section is the following text from a health campaigner, Dr. Vera Shreibner, but the origins of the details are items from the Bulletin of Medical Ethics, published in London in 1994-95, particularly the August 1995 issue:

"The Bulletin of Medical Ethics.....in......the October 1994 article, "Is Your Measles Jab Really Necessary?", stated that during November 1994 the UK Government would be running a mass campaign of measles vaccination with the intention of reaching every child between the ages of five and sixteen......The purpose.....was to prevent an epidemic that would otherwise occur in 1995, with up to 200,000 cases and up to 50 deaths.....(but) between May and August 1994 the notification rate in England and Wales dropped sharply, so there was nothing that clearly suggested an imminent epidemic.....Based on the epidemiology of measles, there was never going to be a measles epidemic in 1995, and there was certainly no justification for concomitant rubella vaccination. The mass campaign was planned as an experimental alternative to a two-dose schedule of MMR. The UK Government knowingly misled parents about the need for the campaign and about the relative risks of measles and measles vaccination. The UK Department of Health broke the European Union’s law about contracts and tendering to ensure that specific pharmaceutical companies were awarded the contracts......Al this must have been extremely fortunate for the drug companies in question, since the supplies of MR (measles and rubella) vaccines, which they’d been left with in 1992 (when two brands of MMR had been hastily withdrawn after a press leak) and for which there was virtually no demand, were soon to go out of date".

(The Bulletin also pointed out that the whole concept of a mass campaign was questionable. The World Health Organisation had indicated such a strategy, but not specifically for developed countries).

The Civil Service Code gives some principles (with my commentary added):

Although there is no evidence whatsoever to suggest any impropriety in this area, it remains a source of concern that, as there is no register of civil servants’ interests, there is no way that the public can verify the matter, one way or the other. This is important when the ordering of all UK vaccine supplies is now centralised in the Department of Health, when major campaigns such as the 1994 "Operation Catch-Up" anti-measles campaign involve major contracts for over seven million doses of vaccine, and if EU competitive tendering rules are reported to have been side-stepped).

The Commissioner for Public Appointments does not cover civil servants within a department. This issue is only covered by a management code within each department. The code stipulates that:

Once again, the problem is that there is no external-to-the-department scrutiny of such interests, or of the degree of departmental enforcement in practice. Given the major increases in the value of pharmaceuticals shares during the 1990s, this appears to be unsatisfactory, particularly in relation to the key sections of the Department of Health.

Part H - Various Experiences Elsewhere

58. Measles Outbreak In The Republic of Ireland

It has been reported by the UK DoH that there has been an epidemic of measles in the Dublin area, and that two children have died:

Autism is reported as rising sharply in Ireland. A survey of Cork found 33 cases in a population of just 13,000 (source: Ms. Miriam Twomey, Chairwoman of the Hope Project, Cork). The children had generally become autistic before the age of two years, and following vaccination.

59. MMR In Japan

The DoH has asserted that Japan doesn’t use MMR and the consequence has been 69 deaths from measles. The UK Channel 4 News and the UK Daily Mail checked out the facts, on 29/01/01 and 7/2/01 respectively:

60. Autism In Finland

(See also Patja et al study)

Part J - Political Initiatives

61. UK All Party Parliamentary Group On Autism (APPGA), Westminster

62. Scottish Parliament, Edinburgh

63. UK Liberal Democrats

64. UK Conservatives

65. US House of Representatives

Other relevant points:

Part K - Coming Events?

66. Recent and Coming Events - UK

67. Ireland

68. United States

69. "Just One More Question, Minister....."

Some sample questions for the media are offered here...

[Vaccination] [MMR]  [Autism & vaccination]  [David Thrower]