PART F - EVIDENCE TO SUGGEST THAT THERE IS A LINK

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 Unpublished paper by Dr.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 Further unpublished US paper, from Dr.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 UK Regulatory and Monitoring Systems

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