It was said that parents started to refuse to vaccinate children after the Article of Wakefield in Lancet which was published in February 1998. If we search PubMed for some statistical data: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1719604/ "The proportion of parents attributing their child's autism to MMR appears to have increased since August 1997." I do not like retrospective research as it is not clear, based either on memories of someone from several years ago or papers which are in their turn based on memories of parents, but anyway - there is a slight timing difference (6 months actually) and I do not really believe that parents pre-viewed Wakefield's and colleagues research results.

As for our case - first the doctor suspected that our son had measles after vaccination and even called vaccine producer to claim it (was refused), said "in the worst case let's suggest he had measles and hope it will be OK". 1 year later our son was diagnosed with autism. If his autism is the result of measles infection or not - we do not know, but it is clear he had a viral infection as a result of vaccination which should normally PROTECT from that infection. It still surprises me how a vaccine-producer representative can diagnose the absence of link ON THE PHONE, contradicting to diagnostics of our doctor (35 years experience) made "in vivo"... Several days after vaccination he started to have fever, rash (first - behind the ears, then on the face, then on the body, then on the extremities (I remember it well, because I called the doctor literally every 2 hours as changes were quite notable), diarrhea, vomiting (did not drink for 3 days, any liquid was thrown up, even 10 ml). All medical records before the vaccination were perfect except that he had bowel problems (frequent diarrhea). After vaccination diarrhea stopped, but then he started to have constipation. He started to walk at 12.5 months, was walking from his dad to me, laughing, pointing, knew several words (we keep records and video), when his dad came from work he crawled to greet him, pointed to animals and objects and named them, "read" books. After 2 weeks after vaccination we took him to walk in the park. He ran away from us like he does not hear, started to turn around, liked spinning objects, no eye contact.

Recently we made immune tests and found that he has an immunosuppression of 48%. Now we have a paper where it is written "prophylactic vaccination is not recommended". If we have this paper before vaccination it is less likely our son have measles.

I am not against vaccination, but against doing it to all kids without taking into the account their immune system's capacity to fight the infection.

That should not be done by simple "doctor thought", but by appropriate laboratory tests before vaccination.

The required tests should be based on proper research - not retrospective, but medical trials, taking into the account that adults immune system is different to kids, that mice passed thousands times more generations than people optimising their sensory system when people optimised their capacity to interact, so the trials on healthy mice would not give any meaningful results.

If humans are ready to have kids at 15 y.o. then humans passed about 15000 generations from their "existence", 3500 generations from the time they started to talk, 500 generations from medical interventions (whic decrease survival optimisation). Mice do not have any medical treatment and their breeding onset is 50 hdays of age. So, even if we suppose they appeared at the same time as "relatively modern" humans (i.e. 200000 years ago) - then they passed 1.46 mln generations. Compare this to 15000 it is 1.445 mln generations more. How that can be compared to people, who on the top are not oriented to survival (i.e. optimisation of their sensory skills), but on medicalisation since birth - it is even ridiculous! Not surprising a language and sensory systems are the first things which are impaired. First one was "recently acquired" and second one regressed instead of being optimised.

So, it is not relevant to compare species quickly changing generations with no medical interventions, which improve their capacities to adapt to changing environment with each generation to humans, who do not improve their survival characteristics.

The better way would be to use computer programs modelling homeostasis changes due to external interventions. That could be one of the tools. Thus, even with that tool (or especially with that tool) research results theoretically could be manipulated.

Competing interests: Mother of the son with autism. Measles infection due to vaccine were claimed by the doctor (denied by vaccine producer on the phone) 1 year before autism diagnostics.

I was appreciative that some readers have taken the opportunity to look at the exciting developments in Autism research most notably by such eminent institutions as the University of California 1 and Johns Hopkins. 2

Further to this there is a number of excellent Distinguished Lecturer Series presented in multimedia format.Sourced at UC Davis MIND Institute.

I have always been concerned that the British Medical Journal and others were ignoring the real contribution parents can make in an open and honest dialogue with health professionals on a range of issues associated with ASD.

Though I was grateful the BMJ drew my attention to Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report.3 I found as a parent of an ASD child information contained at statements 14 to 18 particularly relevant to my families circumstances.

Readers then might be also interested in further research undertaken by The Kennedy Krieger Institute, Center for Autism and Related Disorders, The Johns Hopkins School of Medicine, USA in conjunction with Division of Biostatisics, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University, USA. 4

The research presented as "Development in infants with autism spectrum disorders: a prospective study" reinforces the very real observations of parents and caregivers.

Infants were tested at 6 14 and 24 months using the Mullen Scales of Early Learning.

87 children were selected as either High Risk for ASD or low risk. High risk children were siblings of ASD children Low risk were children from families with no history of ASD.

Results

At 6 months no statistical change evident.

By 14 months the ASD group was beginning to show signifcant performance deficits in all but one area.

By 24 months the ASD group performed significamtly behind all groups including the language delayed group. (LD) Particularly in Gross and fine motor skills as well as receptive language.

Their conclusion that reinforces parental observations.

"Unusual slowing in performance occurred between 14 and 24 months of age in ASD."

Of course their is a variety of hypotheses that can be generated from this information and I make no claim as to what this conclusion may mean . I just suggest that parents were faithfully describing a very real event in their ASD child's development.

regards

Further readings for those interested in all matters pertaining to ASD. I have referenced internet links as this is perhaps the easiest for parents and caregivers.

1. Distinguished Lecturer Series http://www.ucdmc.ucdavis.edu/mindinstitute/videos/video_dls.html#dls11

2. Johns Hopkins Neuroimmunopathology Laboratory research on autism http://www.neuro.jhmi.edu/neuroimmunopath/autism.htm

3. Buie et al Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report http://pediatrics.aappublications.org/cgi/content/full/125/Supplement_1/S1?gca=125%2FSupplement_1%2FS1& 4.Landall,Garrett-Mayer Development in infants with autism spectrum disorders: a prospective study

http://onlinelibrary.wiley.com/doi/10.1111/j.1469- 7610.2006.01531.x/abstract

Competing interests: Father of ASD son. My children are fully immunised on time and schedule. I have never made a claim between vaccination and my son's ASD.

New unorthodox approach to treat inflammatory bowel disease in autism gets approval from the FDA

I read a remarkable report published recently in The Scientist (Vol 25, Issue 2, Page 42)that shows how effective treatment of gut inflammation can reverse the most severe symptoms in autistic individuals. What is perhaps even more remarkable is that this new highly unorthodox treatment now has the stump of approval from the FDA. Why unorthodox? Because it involves feeding autistic patients with live ova of the nematode Trichuris suis, pig whipworm !

The idea for this came from Stewart Johnson (father of a child with autism) who discovered the work of researchers at the University of Iowa who had previously successfully treated patients with Crohn's disease and ulcerative colitis with Trichuris suis ova (TSO) [1-2]. Both Chron's and ulcerative colitis are autoimmune disorders in which the immune system attacks the intestinal walls. Stewart's hypothesis was that parasitic worm infection would modulate his son's immune system and calm the gut inflammation that was causing his disruptive behaviors. He came to this conclusion after reviewing the landmark study by Vargas et al. [3] which showed extensive glial activation and neuroinflammation in the brain of patients with autism. This led Stewart to conclude that indeed, there was a gut-brain connection in autism and that by fixing the gut problem the latter would be fixed as well.

He proposed this treatment to Dr. Eric Hollander from the Montefiore Medical Center University Hospital of the Albert Einstein College of Medicine.

After obtaining permission to administer the treatment from the US Food and Drug Administration (FDA) under "compassionate use" rules, Stewart and Hollander initiated the treatment.

Within 10 weeks of treatment (with 2,500 eggs given every two weeks), the boy's symptoms did no just improve. They vanished. He stopped smashing his head against walls and gouging at his eyes. His psychotic behaviours stopped and the family was finally allowed to have a normal life.

The big question is: what is the mechanism by which TSO modulates the immune system to calm down autoimmune attacks and inflammation in autism ? It was initially assumed that intestinal worms could activate a Th2-type response and as a consequence, suppress the Th1 response, which is usually implicated in autoimmune diseases. However, this hypothesis was later dismissed in favour of more recent research which showed that the mechanism involves direct modulation of regulatory T-cells (T-reg) by the worms. T-reg cells function to suppress activation of the immune system thereby preventing it from attacking the body's own tissues. Research indicates that intestinal worms can induce T-reg cells initially in the gut and that this changes the inflammatory setting which finally results in less inflammation in the brain.

This is good news! Even better is that the FDA finally started thinking outside of the box!

References:

1. R.W. Summers et al., "Trichuris suis therapy in Crohn's disease," Gut, 54:87-90, 2005. 2. R.W. Summers et al., "Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial," Gastroenterology, 128:825-832, 2005. 3. D.L. Vargas et al., "Neuroglial activation and neuroinflammation in the brain of patients with autism," Annal Neurol, 57:67-81, 2005.

Competing interests: None declared

In common with Dr Yazbak, I have no intention of dissecting Brian Deer's article in this rapid response. Instead I too wish to state the grateful thanks of all my family members to those two wonderful Royal Free clinicians, Professors Walker Smith and Murch. They were kind compassionate and very professional, and my Grandson's condition and behaviour improved greatly as a result of their diagnosis and care. My daughter was fully informed and consulted at every stage, including all diagnostic procedures.

My Grandson was properly referred to the Royal Free by his GP and his treatment was paid for by the NHS, which is 'free at the point of use' in the UK. He is still autistic and is still receiving NHS treatment for his bowel problems.

These two outstanding clinicians did not deserve the vilification, which has been their reward for doing their jobs properly and conscientiously, always putting their patients first. I was standing outside the GMC premises in July 2010 when the verdicts were announced. My delight at the total exoneration of Professor Simon Murch was tempered by my anger about Professor Walker Smith and Dr Wakefield both being 'struck off' the Medical Register.

My placard said 'Travesty of Justice'.

Competing interests: My autistic Grandson was treated for his bowel disorder at the Royal Free Hospital by Professors Walker Smith and Murch. (NOT one of the Lancet 12)

In response to Catherina Becker's comment. For parents of non-MMR vaccinated children with gastrointestinal symptoms and developmental regression, I don't think the topic at hand is "whether MMR causes autism with gut problems", but whether gastrointestinal disease triggered by environmental factors lead to brain malfunction in their previously normal children. If we knew what those factors were they could be avoided, even if one of them is a particular vaccine, a combination of vaccines, or a component of vaccines, and then vulnerable children could be shielded from permanent harm.

From my perspective, the most important aspect of Wakefield's 1998 paper is that it highlighted a medical problem in the group of children with regression - one medical problem among many other medical problems that for decades doctors have ignored by attributing physical manifestations of disease to autism, which, thanks to Leo Kanner and Bruno Bettelheim was blamed until only recently on poor parenting and refrigerator mothers breast-feeding their babies their black milk. (1)

We have a group of children with autism spectrum diagnoses whose medical problems (gastrointestinal disease, sub-clinical epilepsy, severe auditory problems and more) are overlooked time and time again because the children carry a psychiatric label, and the only solution doctors have offered to date is medication with a whole raft of dangerous, mind- altering drugs to control their behaviour. (2)

If it were not for Dr Andrew Wakefield, I very much doubt that in 2010 the American Academy of Pediatrics would have even entertained the idea of gastrointestinal disease in children with autistic conditions. I believe we have him to thank for their Consensus Report: "Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs" (2010). (3) They say:

"Care providers should be aware that problem behaviour in patients with ASDs may be the primary or sole symptom of the underlying medical condition, including some gastrointestinal disorders".

The question is:

How much longer must we wait for it to become standard medical practice for children presenting with regression and autistic symptoms to undergo full neurological, audiological, gastrointestinal and immunological testing?

It is surely high time to stop diagnosing babies, toddlers, and small children with lifetime mental disorders without looking for the root cause. Because autistic conditions do not have one cause, but many, the only way to do that is to examine the children as individuals.

Catherina Becker says she is baffled that with Lucija Tomljenovic's scientific training she should associate herself with "the anti-vaccine circus". Thinking people have always questioned the science behind vaccination, its efficacy and its safety. (3) George Bernard Shaw was one. Unfortunately, with very little science to support it, vaccination has become a religion, and anyone who questions its efficacy and/or safety is regarded as a heretic.

The bottom line is whatever side you take, pro-vaccine, pro-some- vaccines, or anti-vaccine, we all want our children to be healthy and mentally-fit, but with 1 in 7 children with neurological disorders today, can we really say in 2011 that they are?

(1) http://www.amazon.com/Empty-Fortress-Infantile-Autism- Birth/dp/B001MSIENO/ref=sr_1_1_title_1_h?s=books&ie=UTF8&qid=1295994362&sr=1 -1

The Empty Fortress: Infantile Autism and the Birth of the Self Bruno Bettelheim (1967)

(2) http://www.medicalnewstoday.com/articles/187386.php

Children With Autism Frequently Receive Psychotropic Medications 04 May 2010

(3) http://www.pediatrics.org/cgi/content/full/125/Supplement_1/S1

Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs Pediatrics 2010;125;S1-S18

(4) http://openlibrary.org/books/OL7164739M/

The_story_of_a_great_delusion_in_a_series_of_matter-of-fact_chapters. The Story of a Great Delusion by William White - Published 1885

Competing interests: My son regressed after vaccines. He has never received the MMR.

"Mistakes are, after all, the foundations of truth, and if a man does not know what a thing is, it is at least an increase in knowledge if he knows what it is not." Carl Jung

In the interests of breaking open this discussion from the simplistic construct of "MMR causes Autism" to the more open hypothesis generating question "What causes Autism ?".

I think both protagonists with varying interests in immunology and neurology should take a constructive look at the research being undertaken at Johns Hopkins Medicine Department of Neurology.

Perhaps they could start from this press release and summary into more substantial research articles.

Brain's Immune System triggered in Autism.1

FAQs: The meaning of neuroinflammatory findings in autism 2

Our Findings on Autism 3

Further they should again take time to avail themselves of research being undertaken at University of California MIND Institute 4.

Once again I should note with clear dissatisfaction that the observations and concerns of parents and caregivers of ASD children are not being properly investigated.

Put away your prejudices and have a "red hot go" at an open and honest dialogue.

1. Press Release http://www.hopkinsmedicine.org/Press_releases/2004/11_15a_04.html

2. FAQ Autism http://www.neuro.jhmi.edu/neuroimmunopath/autism_faqs.htm

3. Our Findings http://www.neuro.jhmi.edu/neuroimmunopath/autism_findings.htm

4. Research Studies http://www.ucdmc.ucdavis.edu/mindinstitute/research/studies.html

Competing interests: Father of ASD son

The recent BMJ editorial, along with several recent publications, have made extremely serious allegations of scientific fraud against Dr. Wakefield and his colleagues in regard to the 1998 Lancet study that supposedly linked the MMR vaccine to gastrointestinal disorders and autism. Even assuming that such fraud was committed -and there is abundant countervailing evidence to suggest that such did not occur- does the use of the term 'fraud' invalidate a legitimate scientific question? The answer is that it does not. The autism spectrum disorders incidence levels have grown explosively since 1992. Claims that such rising levels are due to changes in the gene pool have no scientific validity. Similar claims that changes in diagnostic criteria for ASD are to blame, while partially true, cannot account for the 2000 to 3000% change in ASD. This observation leads inevitably to one remaining conclusion, namely that something in the human environment is the culprit. There are many possible factors that may have increased leading to rising ASD levels. One of these is the significantly increased vaccine schedule for children. Any a priori exclusion of possible factors based on belief rather than evidence is not scientific, but rather reflects a disturbing trend to view anything associated with vaccines and vaccine policy as sacred and beyond scientific scrutiny. Indeed, some who appear to take this view frame their arguments less as scientific critiques and more as ad hominem attacks on the credibility, expertise, or scientific training of any who do what scientists are trained to do: ask questions and seek answers. Assertions that those who do so in respect to any aspect of vaccine safety must therefore be "anti vaccine" and hence not to be taken seriously belies a belief system that is profoundly unscientific. As most readers will know, an ad hominem attack on an opponent's character or credibility is a tacit admission that the logical argument is lost. Such comments have occurred in some letters to the editor on the issue of the Wakefield editorial and have attempted to portray those scientists who attended the recent Vaccine Safety Conference in Jamaica as unreliable because of some alleged bias against vaccines. As one of the organizers of the conference, let me state that an anti-vaccine bias was not the agenda of the meeting. Rather, a number of highly qualified scientists from different fields gathered for an open examination of the issue and in so doing simply fulfilled their fiduciary duties as scientists to seeking the truth.

Competing interests: None declared

To the best of my knowledge, the BMA has not officially commented as yet on Mr. Deer's pieces. There were also precious few rapid responses from British physicians in practice. Maybe they had enough of Deer and his personal vendetta or maybe they were embarrassed by the insults heaped on the Lancet.

The lack of interest in local papers and news outlets has also been very hard to miss.

A review of the rapid responses to the three articles strongly suggests that critical messages are being blocked and that aggressive criticisms of anything remotely pro-Wakefield are being published, lately garnished by the stale "anti-vaccination" label.

Fully aware that I would never be allowed to challenge Mr. Deer or respond to all his allegations, I will not even try.

Were children investigated and treated at the Royal Free Pediatric GI unit "used" for ulterior motives? Did they suffer needlessly and were they subjected to inappropriate work-ups and investigations?

My answer is NO. As I said numerous times in the past: As a pediatrician and the grandfather of a boy who was investigated at the unit, properly diagnosed and remarkably improved, I can attest that he received superb care from Professors Murch and Walker-Smith. We never felt that he had been worked-up for any reason other than his best interest. We have also never seen the slightest hint of a scam.

Over the years, we have come to know two mothers whose children were among "the twelve" and several parents whose children were subsequently investigated. We have never heard a word of criticism about the program at Royal Free from any of them.

The biggest proof that Mr. Deer is imagining demons where they do not exist is that: a) parents were lining up and begging to have their children investigated and treated and b) If the wonderful team of pediatric GI specialists at the Royal Free Hospital decided to resume their research on autistic enterocolitis today, I would bet that lines would form again and families would resume flying in from other countries as they did years ago.

Did Dr. Wakefield commit "Fraud" when he described the original twelve cases? My answer is again NO.

For the sake of brevity, I will only comment on Child 1 who Mr. Deer claims was affected before his MMR vaccination because he could not hear.

Although children with autism are sometimes suspected to have loss of hearing when they start withdrawing, this is always followed by other classical symptoms of the disorder. Such symptoms were not recorded before the child's MMR vaccination.

In fact, children with autism often have hyperacusis and are extremely distressed at the least noise. My grandson could hear a fly much before we did and starting a vacuum cleaner anywhere in the house was enough to throw him into a panic.

More importantly, Child 1 had a visible and physician-diagnosed reason for his decreased hearing: He had purulent otitis media and Mr. Deer knew that.

I respectfully request that criticisms of the 3 papers be published and answered by Mr.Deer

The editors owe the readers at least that.

Competing interests: I am a grateful friend of Dr. Andrew Wakefield

Readers of BMJ Rapid Responses may be a little confused that Fiona Godlee should reply to criticisms of her own journal without reproducing the document to which she was responding. It consisted of nine questions which can be viewed on-line at Age of Autism [1]. It is troubling that in the current debacle BMJ should fear even to publish questions and I append it here so that readers can judge how effectively Dr Godlee has answered them:-

'Dr. Godlee, I submit the following questions and would appreciate your response. Thank you.

'1. Do the BMJ editors stand by their 6 Jan 2011 editorial "Wakefield's article linking MMR vaccine and autism was fraudulent" alleging Andrew Wakefield alone and unassisted committed research fraud?
'This relates to a 1998 Lancet medical journal "early report" calling for more research into a finding of a new bowel syndrome in children exhibiting autistic symptoms?

'2. The editors claim "Wakefield altered numerous facts about the patients' medical histories in order to support his claim to have identified a new syndrome" and base this substantially on a comparison between early general family doctor records and what was reported in The Lancet early report.
'Do the BMJ editors dispute that:
*it was impossible for that to be done by anyone as they have alleged
*it could not have been done by Dr Wakefield
*none of the other 12 expert specialist medical professionals at The Royal Free Hospital London worked from or even saw those "patients' medical histories"
*those experts carried out their own investigations afresh
*Dr Wakefield faithfully reported the data and results provided by his other 12 expert professional colleagues

'3. If these matters are disputed, can the BMJ produce the data and results provided to Dr Wakefield by his 12 colleagues and demonstrate where The Lancet early report diverges?

'4. If the editors cannot produce evidence, do they now retract their editorial and the paper by Mr Brian Deer upon which it is based and which they also published?

'5. Can the editors confirm that neither they nor Mr Deer had sight of or access to the "prospective developmental records" of the 12 Lancet children [the "Red Books"]. 'These were used as part of the basis for detailed clinical histories investigating afresh early signs of disintegrative disorder.

'6. Do the editors agree that family doctors would not have considered "disintegrative disorder" nor looked for early signs.

'7. If the editors still stand by their story how do they account for the fact that those 12 specialist expert medical professionals read and reviewed the Lancet paper before submission for publication, approved Wakefield's report of their work and put their names to the paper?

'8. Do the editors accept that by accusing Dr Wakefield of fraud they are accusing all the other 12 experts?

'9. Do the editors also accuse the authors of the following papers of fraud for claiming to have found the same or a closely similar condition in autistic patients:-

'Balzola F, Barbon V, Repici A, Rizzetto M. Panenteric IBD-like disease in a patient with regressive autism shown for the first time by the wireless capsule enteroscopy: another piece in the jigsaw of this gut-brain syndrome? Am J Gastro. 2005; 979-981. (Italian replication)

'Balzola F, et al. Autistic enterocolitis: confirmation of a new inflammatory bowel disease in an Italian cohort of patients. Gastroenterology.2005;128:Suppl.2;A-303. . (Italian replication)

'Balzola F, et al. Beneficial behavioural effects of IBD therapy and gluten/casein-free diet in an Italian cohort of patients with autistic enterocolitis followed over one year. Gastroenterology, 2006:30; suppl. 2 S1364 A-21. . (Italian replication)

'Chen B, Girgis S, El-Matary W. Childhood autism and eosinophilic colitis. Digestion. 2010;81:127-9. (Canadian replication)

'Galiatsatos P, et al. Autistic enterocolitis: fact or fiction? Can J Gastroenterol 2009;23:95-98. (Canadian replication)

'Gonzalez L, Lopez K, Navarro D, Negron L, Flores L, Rodriguez R, Martinez M, Sabra A. Endoscopic and Histological Characteristics of the digestive mucosa in autistic children with gastrointestinal symptoms. Arch Venez Pueric Pediatr 69;1:19-25 (Venezuelan replication)

'Horvath K et al. Gastrointestinal abnormalities in children with autistic disorder. J Pediatr. 1999;135:559-63. (US replication)

'Krigsman A, Boris M, Goldblatt A et al. Clinical Presentation and Histologic Findings at Ileocolonoscopy in Children with Autistic Spectrum Disorder and Chronic Gastrointestinal Symptoms. Autism Insights 2010;2:1-11 (US replication)'

[1] http://www.ageofautism.com/2011/02/email-the-bmj-editor-asking-these-questions-re-andy-wakefield-editorial.html

Competing interests: Managing Editor, Age of Autism Mother of 3 daughters with autism 16, 14 and 10 years of age.

In regards to Fiona Godlee's quote and reference from Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report Buie etal.1

I would imagine that ASD parents are more rightly concerned about the very strong evidence of an interplay of severe behaviour and bowel conditions.

As was John Walker-Smith who has appeared at all times throughout this controversy as a man of great professional and personal stature as well as a deeply caring and sympathetic doctor.

Walker-Smith had this to say on why the case review was published

"Second, we have noted important behavioural responses in several of the children when their intestinal pathology is treated."2

Those behavioural responses should not be underestimated, because they include self injurious behaviours and violence, as we further explore this issue.

We should then position this comment against our current understanding of ASD bowel conditions with Statement 6 of Godlee's referenced Consensus Statement.

"An emerging literature suggests that individuals with ASDs and gastrointestinal symptoms may be at higher risk for problem behaviors than those with ASDs who do not have gastrointestinal symptoms."1

further to this statement ..

"Problem behaviors are the single most important factor in determining quality of life for individuals with ASDs and their caretakers.33 Vocal and motor behaviors, including problem behaviors such as self-injury and aggression, as well as overall changes in state of being (eg, sleep disturbance or irritability), may be behavioral manifestations of abdominal pain or discomfort in persons with ASDs."1

A full text html or pdf file is available for interested parties to fully avail themselves of one of the most important and overlooked issues in this debate the care of our most vulnerable children.

regards

1. Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report (doi:10.1542/peds.2009-1878C)

2. Autism, inflammatory bowel disease, and MMR vaccine Original Text Simon Murch Mike Thomson John Walker-Smith doi:10.1016/S0140-6736(05)70323-8

Competing interests: Father of ASD son.

Since we published the first of three articles by Brian Deer on the secrets of the MMR scare [1] and a linked editorial [2] on 5 January 2011, the BMJ has been the subject of an orchestrated campaign of emails. In response to questions raised in these emails, we make the following statement.

The BMJ stands by the article and the editorial. The article, which was subjected to peer review and editorial checking, was based on enquiries carried out over some seven years, involving, among other things, interviews with parents of children enrolled in Andrew Wakefield's research. Four such parents are quoted in the article. As made clear in the article, the core data on which the findings were based were evidenced, except in the case of one child, by the transcript of a General Medical Council fitness to practise hearing which sat between July 2007 and May 2010.

In many of the emails we have been sent, it is suggested that Andrew Wakefield did not have access to GP records and therefore could not be responsible for discrepancies between those records and what was published in the Lancet in February 1998. The case we presented against Andrew Wakefield that the 1998 Lancet paper was intended to mislead is not critically reliant on GP records. It is primarily based on Royal Free hospital records, including histories taken by clinicians, and letters and other documents received at the Royal Free from GPs and consultants.

We draw attention to the finding of the fitness to practise panel, on which we are entitled to rely, that "the project reported in the Lancet paper was established with the purpose to investigate a postulated new syndrome and yet the Lancet paper did not describe this fact at all. Because you [Wakefield] drafted and wrote the final version of the paper, and omitted correct information about the purpose of the study or the patient population, the panel is satisfied that your conduct was irresponsible and dishonest."

Contrary to other suggestions contained in the emails, we made no allegation of dishonesty against Andrew Wakefield's co-authors, or indeed against anybody else. As the GMC panel heard, it was Andrew Wakefield who wrote the Lancet paper, using data which he anonymised, with little oversight by other authors. We confirm that under the uniform requirements for manuscripts submitted to biomedical journals all authors should be in a position to speak to data, but the evidence is that in this case they were not.

We are aware of recent claims made by Andrew Wakefield that "new documents have come to light" purportedly confirming his claims in the Lancet. The material he cites was presented to the GMC panel two and a half years ago. Andrew Wakefield was last year erased from the medical register and he has chosen not to appeal that decision. As indicated, the very many charges proven against him include dishonesty in his research.

We are unaware of any peer reviewed paper replicating Andrew Wakefield's research or confirming his claims to have identified a new syndrome of regressive autism and inflammatory bowel disease associated with MMR vaccination. With respect to gastrointestinal issues, we draw attention to an authoritative consensus statement published last year by experienced specialists in this field [3] and particularly to statement 4: "The existence of a gastrointestinal disturbance specific to persons with ASDs (eg 'autistic enterocolitis') has not been established."

Fiona Godlee, Editor in Chief, BMJ

References

1. Deer B. How the case against the MMR vaccine was fixed. BMJ 2011; 342:c5347 doi: 10.1136/bmj.c5347

2. Godlee F, Smith J, Marcovitch H. Wakefield's article linking MMR vaccine and autism was fraudulent. BMJ 342:doi:10.1136/bmj.c7452

3. Buie P, Campbell DB, Fuchs GJ, et al. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus statement. Pediatrics 2010;125;S1-S18.

Competing interests: FG is editor in chief of the BMJ and responsible for all it contains.

In response to Catherina Becker's comment ( 24 January). For parents of non-MMR vaccinated children with gastrointestinal symptoms and developmental regression, I don't think the topic at hand is "whether MMR causes autism with gut problems", but whether gastrointestinal disease triggered by environmental factors lead to brain malfunction in their previously normal children. If we knew what those factors were they could be avoided, even if one of them is a particular vaccine, a combination of vaccines, or a component of vaccines, and then vulnerable children could be shielded from permanent harm.

From my perspective, the most important aspect of Wakefield's 1998 paper is that it highlighted a medical problem in the group of children with regression - one medical problem among many other medical problems that for decades doctors have ignored by attributing physical manifestations of disease to autism, which, thanks to Leo Kanner and Bruno Bettelheim was blamed until only recently on poor parenting and refrigerator mothers breast-feeding their babies their black milk. (1)

We have a group of children with autism spectrum diagnoses whose medical problems (gastrointestinal disease, sub-clinical epilepsy, severe auditory problems and more) are overlooked time and time again because they carry a psychiatric label, and the only solution doctors have offered to date is medication with a whole raft of dangerous, mind-altering drugs to control their behaviour. (2)

If it were not for Dr Andrew Wakefield, I very much doubt that in 2010 the American Academy of Pediatrics would have even entertained the idea of gastrointestinal disease in children with autistic conditions. I believe we have him to thank for their Consensus Report: "Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs" (2010). (3) They say:

"Care providers should be aware that problem behaviour in patients with ASDs may be the primary or sole symptom of the underlying medical condition, including some gastrointestinal disorders".

The question is:

How much longer must we wait for it to become standard medical practice for children presenting with regression and autistic symptoms to undergo full neurological, audiological, gastrointestinal and immunological testing?

It is surely high time to stop diagnosing babies, toddlers, and small children with lifetime mental disorders without looking for the root cause. Because autistic conditions do not have one cause, but many, the only way to do that is to examine the children as individuals.

(1) http://www.amazon.com/Empty-Fortress-Infantile-Autism- Birth/dp/B001MSIENO/ref=sr_1_1_title_1_h?s=books&ie=UTF8&qid=1295994362&sr=1 -1

The Empty Fortress: Infantile Autism and the Birth of the Self Bruno Bettelheim (1967)

(2) http://www.medicalnewstoday.com/articles/187386.php

Children With Autism Frequently Receive Psychotropic Medications 04 May 2010

(3) http://www.pediatrics.org/cgi/content/full/125/Supplement_1/S1

Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs Pediatrics 2010;125;S1-S18

Competing interests: My son regressed after vaccines. He has never received the MMR.

I have come to these articles to try to educate myself on the Wakefield issue firsthand, seeking more than snippets and opinions from other sources (both pro and con). However, I am finding it difficult to get past a clear need for editorial review of a simple article by the journal's editor in chief. I am afraid it does not reflect well on the quality of content, nor the rigor with which it is reviewed prior to publication.

Please correct the error in the following paragraph, which references a mumps outbreak in Essen Germany. The article cited to support this clearly indicates the outbreak was of measles, not mumps:

"Any effect of the scare on the incidence of mumps remains in question. In epidemics in the UK, the US, and the Netherlands, peak prevalence was in 18-24 year olds, of whom 70-88% had been immunised with at least one dose of the MMR vaccine.21 22 Any consequence of a fall in uptake after 1998 may not become apparent until the cohorts of children affected reach adolescence. One clue comes from an outbreak in a school in Essen, Germany, attended by children whose parents were opposed to vaccinations. Of the 71 children infected with mumps, 68 had not been immunised.23"

23 Roggendorf H, Mankertz A, Kundt R, Roggendorf M. Spotlight on measles 2010: measles outbreak in a mainly unvaccinated community in Essen, Germany, March-June 2010. Euro Surveill2010;15:2

Regards,
KB

Competing interests: Parent of ASD Child

It surely has not escaped Catherina Becker's notice that the Hornig paper [1] contradicts its headline conclusion in the discussion. Having detected measles RNA in the ileum of two patients - one autistic case, and one non-autistic control but both having had MMR and bowel disease - the paper frankly states:

"Our results differ with reports noting MV RNA in ileal biopsies of 75% of ASD vs. 6% of control children...Discrepancies are unlikely to represent differences in experimental technique because similar primer and probe sequences, cycling conditions and instruments were employed in this and earlier reports; furthermore, one of the three laboratories participating in this study performed the assays described in earlier reports. Other factors to consider include differences in patient age, sex, origin (Europe vs. North America), GI disease, recency of MMR vaccine administration at time of biopsy, and methods for confirming neuropsychiatric status in cases and controls."

The only proper conclusion would have been that more research was needed.

[1] Hornig et al, 'Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study', http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003140

Competing interests: Autistic son

Obviously, vaccine safety is an important matter. However, it is not the matter this editorial is about.

The matter at hand is that Andrew Wakefield made up an entire paper, only very loosely based on data/facts, as it seems motivated by financial interest and causing both injury to vulnerable children and unwarranted fears of a vaccine, which lead to further damage to even more children (through entirely preventable measles outbreaks) and anguish to parents (who thought or still think they caused damage to their child by letting them be vaccinated).

Wakefield's claims have never been independently duplicated. Why is that, when there were a number of attempts in the past 12 years to specifically verify the connection between autism, gut problems and autism, most notably Hornig et al.(1)? The Cochrane report on the MMR vaccine does not justify Andrew Wakefield's actions.

(1) http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0003140

Competing interests: I have blogged about these issues.

Dear Sir,

May I suggest some useful quotes which might contribute to constructive discussion:

Cooper LZ, Larson HJ, Katz SL. Protecting public trust in immunization. Pediatrics 2008;122(1):1-5.

"In fact, there is no more dramatic documentation of the shortfalls in research on immunization safety than the findings of a series of Institute of Medicine review committees. At the request of the Department of Health and Human Services (DHHS), these expert review committees were established to evaluate specific hypotheses about harm from vaccines. Over the past 15 years, more than half of the allegations reviewed by the committees have concluded that "evidence is inadequate to accept or reject a causal relationship."

Blume S. Anti-vaccination movements and their interpretations. SocialScience & Medicine 2006;62(3):628-42.

"A crucial finding of Pilgrim and Roger's study bears on the attitude of professionals and their apparent resistance to the idea of parents wishing to make their own informed choices. Professionals seem frequently to have been seen as an obstacle to informed choice, rather than a source of advice and information. In other words, vaccination may be voluntary in theory, but that is not how most health professionals treat it in practice. The information literature they are given, in the view of these parents, reflects this same point of view: not designed to inform but to induce conformity. Full of glossy pictures, propaganda, nothing whatever on possible risks or side effects, on the duration of protection, on systemic effects on the child's immune system. It is of no help in trying to make a personal decision since that isn't its purpose: something particularly resented by highly educated parents accustomed to making reasoned decisions in most aspects of their lives. The social pressure exerted on parents who ask awkward questions, trying to reason things out for themselves, is deeply resented" p.637

(So too it seems are doctors, asking awkward questions, deeply resented...)

"To focus attention on vociferous opponents of vaccination, and to expound ways in which they can be countered (e.g. Leask & McIntyre, 2003) is to unite public health and medical professionals behind a banner of reason and rationality. At the same time it diverts attention from other sources of dissatisfaction. The unwelcome alternative is to raise serious, complex and potentially disruptive questions regarding the ways in which medical professionals behave: a critique that, as we saw, was indeed articulated by mothers interviewed in both Britain and the Netherlands." p.639

"Decades of emphasis on personal rights and responsibilities have encouraged growing number of educated parents, many of whom have already learned to express their preferences in opting for natural childbirth for example, to reason for themselves. For such parents the vaccination literature available and the attitudes of practitioners are deeply dissatisfying. Rogers and Pilgrim come to a similar conclusion. They point to a contradiction between the NHS policy emphasis on patients' rights to informed consent and practices around vaccination that fail to respect those rights. What we then see is an ideological conflict at the very heart of public health, in which individual rights on the one hand, and the expert articulation of the common good on the other, are pitted one against the other." p.639

"Until recently the tendency was to assume that parental doubts have no basis in fact and therefore do not merit serious consideration. There was no interest in the possibility that resistance to vaccination might follow rationally either from reasonable beliefs or justifiable concerns. ''Where consideration has been given to parents' views they tend to be portrayed as irrational or driven by neurotic anxiety,'' wrote Rogers and Pilgrim in 1994. Today, still, some are convinced that anti- vaccinationists are simply misinformed and irrational (or anti-rational). They must be made to see the truth of the matter. If their claims regarding vaccine risks can no longer be ignored, then they must be addressed and rebutted by appeal to a superior science. Not only is this sociologically inadequate, it is unlikely to have the desired effect either. 'Sociologically inadequate' because a sociological analysis must see both sides as mutually engaged in a process of contestation, in which the reflexive analysis of (shared) experience, differences in the assessment of risk, and the place of expertise in democratic decision making are all at stake. 'Ineffective' because what is being contested goes far beyond establishment of some objective measure of vaccine-risk, to the heart of modern citizenship and democratic politics." p. 640

"Concordance in immunization policy, he writes, ''must mean more than evidence-based health care simplistically interpreted.'' It should mean ''not only applying the evidence to the individual, but also dialogue between perspectives based on different views of the world. It means an exchange of views and mutual respect between these very different views'' (Vernon, 2003). He recognizes how great a step this will be for the health professions. Could dialogue based on ''mutual respect'' produce the desired effects?" p.640

I repeat Blume's question: ...."Could dialogue based on ''mutual respect'' produce the desired effects?"....

Hilary Butler.

Competing interests: Toothcombing bad science is an addictive hobby.

I agree with Lucija

My son was adversly affected by the MMR at 15 months. His story so mirrors many other parents stories by becoming non-verbal and having dietary, behavioural, learning, sleeping problems. To add to that my son has bowel and gut problems and at the age of 8 started to have seizures. We helped the seizures by going on a g/f and c/f diet plus supplements that he was deficient in. The seizures went away but came back with a vengance at the age of 15. Now he is on medication to control his seizures but he is not able to get out of bed most days and I worry for his state of mind and health and that is why I am very serious about getting my message across to warn others of the dangers. I waited 14 years to hear my son say "Ma" and he is saying a few words now and can let me know if he wants something or not. Not all will suffer the way our children did from the adverse effects of the MMR but eventually the population will suffer if we allow un-safe vaccines. My son is 18 now, and I am not anti-vaccine I just want safe vaccines.

Competing interests: Mum of MMR vaccine damaged son

Dr. Tomljenovic's answer to my letter is full of them.

Of course critical analyses of vaccine safety doesn't make one "anti- vaccine", but speaking on anti-vaccine conferences and uncritically copying and pasting bad and/or misinterpreted science from anti-vaccine web sites makes one anti-vaccine.

To publically raise doubt about whether the measles vaccine actually works, reveals biomedical illiteracy. Claims like "If you search the literature you will find that outbreaks of infectious diseases frequently occur in fully vaccinated populations" identify the anti-vaccine activist, deliberately misrepresenting the published evidence:

Gustavson et al (http://www.ncbi.nlm.nih.gov/pubmed/3821823) describe what we know to date: 1xMMR will leave about 5% of vaccinees non-immune (in this case 4.1%), and "none of the 1732 seropositive students contracted measles.".

Tugwell et al (http://www.ncbi.nlm.nih.gov/pubmed/14993534) describe an outbreak of chicken pox with an attack rate of 12% in children vaccinated once, which is actually in line with the incidence second varicella infections in patients who previously had the disease (http://www.ncbi.nlm.nih.gov/pubmed/12042544) and roughly a quarter of the incidence in unvaccinated children (although there were very few in that particular outbreak this is what is commonly observed). The 1x varicella schedule has recently been estimated to have prevented about 50'000 hospitalisations in the US from 2000 to 2006 (http://www.ncbi.nlm.nih.gov/pubmed/21199857).

Both in smaller outbreaks in the US (e.g. 2008 San Diego, 11 cases, all unvaccinated http://www.cdc.gov/mmwr/preview/mmwrhtml/mm57e222a1.htm) and larger outbreaks (e.g. 1999/2000 Coburg, Germany, 1200 cases, 1100 unvaccinated http://www.aerzteblatt.de/v4/archiv/artikel.asp?id=39670), the risk of contracting measles was up to 50 times higher in unvaccinated children than in vaccinated.

The anti-vaccine arguments of Dr. Tomljenovic have been debunked over and over again.

Competing interests: I have previously blogged on this issue.

Eileen Nicole Simon writes:

"Thank you, John Stone, for pointing out the paper by Yap et al. on urinary metabolite differences in autism ... The next step must be to try to understand how abnormal metabolites affect the brain in a way that leads to the characteristic disorders of language and social obliviousness exhibited by children with autism."

That, of course, is one line of enquiry, but rather more relevantly we have right to ask in the present context how three doctors were successfully prosecuted for effectively fabricating GI abnormalities in autistic children when according to this study - which was published within days of the conclusion of the hearing - virtually all autistic children have them.

Simon speaks of her sad life as a mother of an autistic child of 48 years. And we can only conclude that the medical and psychiatric professions will have failed both miserably with their closed minds and closed ranks.

Competing interests: Autistic son

And I repeat: Being pro-vaccine safety does NOT make one anti-vaccine. It would be like saying someone was anti-car if they supported the Toyota 2010 recall of 1.53 million cars (due to a faulty brake master cylinder seal that potentially could have resulted in brake fluid leakage). Or that someone was anti-food if they opposed GMO foods.

I am NOT anti vaccine, I am anti bad science. The reason so many dismiss even the possibility that vaccine can cause damage is because they believe this to be true. This is religion and not science.

And to believe the media hypes about the measles epidemic is not exactly scientific either. Has there been an actual study to show how many of the children who contracted measles were actually vaccinated and how many non-vaccinated? If you search the literature you will find that outbreaks of infectious diseases frequently occur in fully vaccinated populations [1,2] most likely because vaccines suppress Th1 cellular immunity which is inherently far more effective against viral infections [3,4]. This is also the reason why there are increasing efforts to develop vaccines which stimulate Th1 responses [5,6].

[1] Gustafson TL, Lievens AW et al. (1987) Measles outbreak in a fully immunized secondary-school population. NEJM 316(13), 771-4.

[2] Tugwell BD, Lee LE, Gillette H, Lorber EM, Hedberg K, Cieslak PR (2004) Chickenpox outbreak in a highly vaccinated school population. Pediatrics 113, 3 Pt 1, 455-459.

[3] Makidon PE et al. (2008) Pre-clinical evaluation of a novel nanoemulsion-based hepatitis B mucosal vaccine. PLoS One 3, e2954.

[4] Israeli E, Shoenfeld Y et al. (2009) Adjuvants and autoimmunity. Lupus 18:1217-1225.

[5] Geissler M, Tokushige K, Chante CC, Zurawski VR Jr, Wands JR (1997) Cellular and humoral immune response to hepatitis B virus structural proteins in mice after DNA-based immunization. Gastroenterology 112: 1307-1320.

[6] Schirmbeck R, Zheng X, Roggendorf M, Geissler M, Chisari FV, et al. (2001) Targeting Murine Immune Responses to Selected T Cell- or Antibody-Defined Determinants of the Hepatitis B Surface Antigen by Plasmid DNA Vaccines Encoding Chimeric Antigen. J Immunol 166: 1405-1413.

Competing interests: None declared

It is really very troubling if exchanges in BMJ cannot take place without flying insults. Admittedly, Catherine Becker's reference to "the anti-vaccine circus" is somewhat milder that some we have seen here but what is wrong with articulating concerns about vaccine safety? If the message is that you are no longer allowed to do it, what insurance could there ever be about the programme not spinning wildly out of control? And what is the scientific base, as opposed to its ideological one?

As it is Cochrane tells us very little positive about the safety of MMR, and nothing in relation to autism:

"No credible evidence of an involvement of MMR with either autism or Crohn's disease was found."

A statement which is virtually meaningless given that none of the six autism studies reviewed was rated of low risk of bias, and the Cochrane paper did not even tackle issues of conflict, many of which were undisclosed: i.e. on their own account they did not find anything but they were poor studies ("largely inadequate"). They did approve of the one GI related study they reviewed but it was paid for and authored by the US Centers for Disease Control and data subsequently placed out of reach - so once again conditions institutional bias and absolute opacity pertain [1].

If you cannot report or investigate adverse vaccine events without scorn and hatred being heaped on you, where are the conditions in which actual science as opposed to reasons of state can flourish?

[1] http://www.bmj.com/content/339/bmj.b3658.extract/reply#bmj_el_220537

Competing interests: Autistic son

I recently came across a document that was issued to the government in 1968, entitled Notes on the use and storage of Measles vaccine (live attenuated) for routine vaccines.

http://www.scribd.com/doc/31707379/Notes-on-the-Use-and-Storage-of- Measles-Accine-Live-Attenuated-for-Routine-Vaccination

In section 7 the document clearly states that measles vaccine should not be given to children under 9 months of age as it fails to immunize them, instead it should be given to children in their 2nd year of life.

In section 8, the document further states that: "An interval of three to four weeks should normally be allowed to elapse between the administration of measles vaccine and any other vaccine, whichever is given first."

Currently measles is given as an MMR shot (essentially-3 vaccines in one) at 12-13 months of age. In UK, kids will on the same day also receive a PCV shot (Pneumococcal). Thus, the UK immunization practices completely violate the recommendations outlined in the 1968 document.

Not only that, but plans appear to be underway to essentially vaccinate children against 6 diseases at the same time (Hib/MenC, MMR and pneumococcal).

http://www.dh.gov.uk/en/MediaCentre/Statements/DH_122026

The UK Department of Health claims that:

"Independent scientific research has shown that providing these vaccines at the same time is safe, effective and more convenient for parents."

No reference is quoted. I would REALLY like to see this independent research.

Competing interests: None declared

Lucija Tomljenovic asks why Andrew Wakefield's findings were duplicated in 5 other countries. The answer is easy:

They were not.

The findings in the since retracted Lancet paper were reported as follows:

"We have identified a chronic enterocolitis in children that may be related to neuropsychiatric dysfunction. In most cases, onset of symptoms was after measles, mumps, and rubella immunisation."

There has not been an independent verification of this triad of results, also not in the list Dr. Tomljenovic provides (1), which comprises case reports, conference proceedings and papers of colleagues of Wakefield's in journals he edited, as Debajyoti Datta rightly points out (2).

The case of bowel inflammation in one autistic adult and two editorials from a time when the extent of data manipulation in the Lancet paper were still unclear (2000 and 2005) (3) don't "duplicate" Wakefield's findings and the reference to the Cochrane's 2005 review of the MMR vaccine (4) is a typical anti-vaccine canard. The topic at hand is whether MMR causes autism with gut problems - the same Cochrane Review answers precisely this question:

"No credible evidence of an involvement of MMR with either autism or Crohn's disease was found."

I was wondering why a post-doctoral fellow, with free access to the biomedical literature, an associate editor of a biomedial journal herself (5), with no declared conflict of interest, would indiscrimately copy and paste from anti-vaccine pages defending Andrew Wakefield, but quickly found that Dr. Tomljenovic has recently spoken on the same anti-vaccine conference as Andrew Wakefield (6), which might explain her bias. The willingness of someone with scientific training to associate with the anti -vaccine circus is still baffling.

(1) http://www.bmj.com/content/342/bmj.c7452.full/reply#bmj_el_248023

(2) http://www.bmj.com/content/342/bmj.c7452.full/reply#bmj_el_248215

(3) http://www.bmj.com/content/342/bmj.c7452.full/reply#bmj_el_248456

(4) http://www2.cochrane.org/reviews/en/ab004407.html

(5) http://www.j-alz.com/about/board.html

(6) http://vaccinesafetyconference.com/speakers.html

Competing interests: I have previously blogged about this issue.

Actually the second reference that I cited is easily found as it is by Nature Publishing Group:

http://www.nature.com/ajg/journal/v100/n4/full/ajg2005166a.html

The American Journal of Gastroenterology (2005) 100, 979-981; doi:10.1111/j.1572-0241.2005.41202_4.x

Panenteric IBD-Like Disease in a Patient with Regressive Autism Shown for the First Time by the Wireless Capsule Enteroscopy: Another Piece in the Jigsaw of this Gut-Brain Syndrome?

"A 28-yr-old male with regressive autism recently came to our attention with unexplained microcytic anemia requiring intravenous iron supplementation. Severe constipation with bloating and abdomen distension and symptoms of gastroesophageal reflux were reported by parents. Gastroscopy under general anesthesia revealed hemorrhagic gastritis with inflammatory pseudopolyps that reached the pylorum with a "pearl necklace" appearance. The biopsies in the stomach and duodenum confirmed the chronic active inflammation whereas those in the second part of the duodenum were inconsistent with celiac disease. The whole colon and the terminal ileum were macroscopically normal at colonoscopy, whereas random biopsies showed a chronic severe active mucosal inflammation (intraepithelial lymphocytes and eosinophyls infiltrations and villous focal atrophy with reactive lymphoid nodular with intraepithelial CD3 and mucosal CD8), compatible with active IBD. The wireless enteroscopy capsule (GIVEN? Imaging Diagnostic System), revealed areas of patchy erythema, mucosal erosions, and ulcers in both jejunum and ileum (Fig. 1A-D). A panenteric IBD-like disease, consistent with previous descriptions of autistic enterocolitis, was finally diagnosed."

I also found several editorials which suggest that Andrew Wakefield's hypothesis should not be discarded. For example:

Nature Publishig Group

The American Journal of Gastroenterology (2000) 95, 2154|[ndash]|2156; doi:10.1111/j.1572-0241.2000.03247.x Autism and the gastrointestinal tract

"Wakefield et al. (13) are to be congratulated on opening yet another window onto the ever-broadening spectrum of gut|[ndash]|brain interactions. Their findings raise many challenging questions that should provoke further much-needed research in this area, research that may provide true grounds for optimism for affected patients and their families."

European Journal of Gastroenterology & Hepatology 2005, Vol 17 No 8

The intestinal lesion of autistic spectrum disorder

"This editorial briefly reviews the significance of lymphoid nodular hyperplasia in the intestinal tract of children with autistic spectrum disorder. The distinction between physiological and pathological lymphoid hyperplasia of the intestinal tract is of importance in the context of a possible causative link with autism. A primary intestinal lesion may occur as part of the broad spectrum of immunological disorders to which autistic children are prone. This could result in increased intestinal permeability to peptides of dietary origin which may then lead to disruption of neuroregulatory mechanisms required for normal brain development. Alternatively, there could be a primary defect in the translocation and processing of factors derived from the intestinal lumen. These possibilities deserve further investigation and should not be lost in the fog of the controversy regarding the role of measles/mumps/rubella vaccination in the aetiology of autistic spectrum disorder."

As for the alleged safety of the MMR, a simple google search also reveals a most comprehensive study done on this subject, by the respected Cochrane Review (October 2005).

Although the review found no significant association between MMR and autism, Chron disease etc (it did however find that MMR vaccine was likely to be associated with benign thrombocytopenic purpura, parotitis, joint and limb complaints and febrile convulsions within two weeks of vaccination and aseptic meningitis (mumps) (Urabe strain-containing MMR)), none of the 31 studies included in the review met the Cochrane Collaboration's methodological criteria.

One of the major conclusions from the Cochrane's 2005 MMR review was:

"The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate."

http://www2.cochrane.org/reviews/en/ab004407.html

Science should be based on evidence, not dogma.

Competing interests: None declared

Thank you, John Stone, for pointing out the paper by Yap et al. on urinary metabolite differences in autism [1]. The next step must be to try to understand how abnormal metabolites affect the brain in a way that leads to the characteristic disorders of language and social obliviousness exhibited by children with autism.

Yap et al. discuss possible disruption in the tryptophan-serotonin- melatonin pathway. In my own dissertation research, on long-term effects of neonatal asphyxia in laboratory rats, we found a male-female difference in brain serotonin synthesis, and initial growth retardation of male pups [2]. So many scornful people asked back then how relevant such findings could be for understanding autism, and I have to admit that both findings were too non-specific to have any direct bearing on autism.

My son with autism is now 48 years old, and I have spent most of my sad life trying to understand autism. I have come to realize that the current scientific obsession with "empirical research" has led to neglect of important existing evidence in the medical literature. Too much recent research on autism has produced a smoke screen of "evidence" that leads nowhere. This is my criticism of research that does not include the brain.

Understanding the brain systems involved in language development is what is most important. Note that the language areas of the cortex are not fully developed until 4 to 5 years after birth [3]. But children begin learning to speak "by ear" long before that, and a diagnosis of autism is usually made by the age of 3 or 4.

The article on asphyxia at birth by William Windle in the October 1969 issue of the Scientific American drew my attention to the auditory system [4]. That was just when I was beginning my graduate studies, and then I discovered the papers on blood-flow in the brain, and the finding that circulation and metabolism are greatest in the auditory pathway [5].

Auditory nuclei in the brainstem are exposed to greater amounts of any potentially toxic substance in the circulation. Asphyxia plus bilirubin or thimerosal or phenylpyruvic acid or aberrant metabolites from sulfation deficiency in the liver is double trouble (or more), and likely to impair an infant's ability to begin understanding speech.

References

[1] Yap IK et al. Urinary metabolic phenotyping differentiates children with autism from their unaffected siblings and age-matched controls. J Proteome Res. 2010 Jun 4;9(6):2996-3004.

[2] Simon N, Volicer L (1976) Neonatal asphyxia in the rat: greater vulnerability of males and persistent effects on brain monoamine synthesis. J Neurochem. 1976 May;26(5):893-900.

[3] Moore JK. Maturation of human auditory cortex: implications for speech perception. Ann Otol Rhinol Laryngol Suppl. 2002 May;189:7-10.

[4] Windle WF. Brain damage by asphyxia at birth. Sci Am. 1969 Oct;221(4):76-84.

Competing interests: Mother of a son with autism

I wonder if Eileen Nicole Simon is aware of this study:-

'Urinary metabolic phenotyping differentiates children with autism from their unaffected siblings and age-matched controls.

Yap IK, Angley M, Veselkov KA, Holmes E, Lindon JC, Nicholson JK.

J Proteome Res. 2010 Jun 4;9(6):2996-3004.

'Autism is an early onset developmental disorder with a severe life- long impact on behavior and social functioning that has associated metabolic abnormalities. The urinary metabolic phenotypes of individuals (age range=3-9 years old) diagnosed with autism using the DSM-IV-TR criteria (n = 39; male = 35; female = 4), together with their nonautistic siblings (n = 28; male = 14; female = 14) and age-matched healthy volunteers (n = 34, male = 17; female = 17) have been characterized for the first time using (1)H NMR spectroscopy and pattern recognition methods. Novel findings associated with alterations in nicotinic acid metabolism within autistic individuals showing increased urinary excretion of N-methyl-2-pyridone-5-carboxamide, N-methyl nicotinic acid, and N- methyl nicotinamide indicate a perturbation in the tryptophan-nicotinic acid metabolic pathway. Multivariate statistical analysis indicated urinary patterns of the free amino acids, glutamate and taurine were significantly different between groups with the autistic children showing higher levels of urinary taurine and a lower level of urinary glutamate, indicating perturbation in sulfur and amino acid metabolism in these children. Additionally, metabolic phenotype (metabotype) differences were observed between autistic and control children, which were associated with perturbations in the relative patterns of urinary mammalian-microbial cometabolites including dimethylamine, hippurate, and phenyacetylglutamine. These biochemical changes are consistent with some of the known abnormalities of gut microbiota found in autistic individuals and the associated gastrointestinal dysfunction and may be of value in monitoring the success of therapeutic interventions.'

http://www.ncbi.nlm.nih.gov/pubmed/20337404

Thirteen years after the Lancet paper I am not sure how anyone is in a position to seriously dispute the GI dimension of autism, irrespective of etiology. I certainly would not dismiss Eileen's concern about cord clamping expressed below either, but perhaps you have to look at a complex of events and not just one.

Competing interests: Autistic son

Autism is a neurological disorder. Therefore impairment within specific areas of the brain must be the focus of research. Autism is first and foremost a very characteristic disorder of language development [1]. What systems between birth and age 3 or 4 must be intact for a child to learn to speak? What causes of injury affect language learning in infancy?

Autism is associated with many etiological factors. Phenylketonuria was formerly associated with autism, and abnormal metabolites like phenylpyruvic acid may have been toxic to the brain. Exposure to alcohol and valproic acid during gestation are also associated with autism. Alcohol has long been known to affect brainstem centers. Anoxic birth is also associated with autism and produces ischemic lesions of the brainstem in a pattern similar to that caused by alcohol. The auditory system is prominently affected by anoxia at birth or prenatal exposure to alcohol [2, 3]. The auditory system is clearly important for learning to speak. Valproic acid appears to have a specific effect on language development [4].

The language disorder of children with autism is different from aphasias caused by damage of Broca's or Wernicke's areas in the cortex [1]. Other neurological handicaps of autistic children are different from those of children with cerebral palsy. The idea that GI disturbance starves the brain is too non-specific.

GI disorders have long been associated with abuse of alcohol (and other drugs), but toxic impairment of brainstem autonomic centers is a more likely explanation for gastrointestinal dysfunction in alcoholism [5].

Gastrointestinal inflammation is not unique to autism. Fraudulent or not, the data on GI problems observed in children are not particularly relevant to autism.

References

[1] Simon N. Echolalic speech in childhood autism. Consideration of possible underlying loci of brain damage. Arch Gen Psychiatry. 1975 Nov;32(11):1439-46.

[2] Windle WF. Brain damage by asphyxia at birth. Sci Am. 1969 Oct;221(4):76-84.

[3] Vingan RD et al. Cerebral metabolic alterations in rats following prenatal alcohol exposure: a deoxyglucose study. Alcohol Clin Exp Res. 1986 Jan-Feb;10(1):22-6.

[4] Meador KJ et al. for the NEAD Study Group. Foetal antiepileptic drug exposure and verbal versus non-verbal abilities at three years of age.Brain. 2011 Jan 11. [Epub ahead of print]

[5] Neuburger K. Wernickesche Krankheit bei chronischer Gastritis. Ein Beitrag zu den Beziehungen zwischen Magen und Gehirn [Wernicke's disease in the presence of chronic gastritis. A conribution to the relationship between stomach and brain]. Zeitschrift fur die gesamte Neurologie und Psychiatrie 1937; 160:208-225.

Competing interests: Mother of a son with autism

I find it very hard to believe that the BMJ allowed Rebecca Fisher to post at all. Their standards have slipped. Rebecca Fisher who says she is a executive publicist should have her website banned www.jabloonies.com. She should not be allowed to make fun out of parents whose children have been damaged by un-safe vaccines. I commend all who seek the truth and Alex Snelgrove tells it how it is for most parents in this tragic situation.

Competing interests: Mum of MMR vaccine damaged son

Lucija Tomljenovic lists nine articles in support of Wakefield's Lancet study. However, it should be mentioned that the first four articles and the seventh reference are not available in a search of Pubmed, most likely they are not indexed.

The fifth study referenced reports a case-series of 36 children where the chief finding was reflux oesophagitis, gastritis and duodenitis. It is not apparent how a finding of reflux oesophagitis can support a finding of ileal-lymphoid- nodular hyperplasia as reported in the Wakefield study.

The sixth reference is a correspondence about findings of ilieal- lymphoid-nodular hyperplasia in two patients with attention-deficit- hyperactivity disorder who were allergic to different foods. This was in an investigation which was looking at food allergy and the immunological involvement of the gut as a central focus for injury of other target organs (skin, lungs and G.I tract, not the brain). Again it's not apparent how this is duplicating Wakefield's Lancet study.

The last two references discuss three cases, two of which describe eosinophillic oesophagitis and gastritis. Again how oesophagitis and gastritis is supporting ileal-lymphoid- nodular hyperplasia is not apparent.

A simple search of Pubmed lists enough good quality research refuting the link between MMR and autism. I am giving one as reference.

Reference -

1. DeStefano F. Vaccines and Autism: Evidence Does Not Support a Causal Association. Clinical Pharmacology & Therapeutics 82, 756-759 (December 2007)

Competing interests: None declared

I agree with Mark Struthers that David N. Andrews appears to be outraged that my son with regression had been given a diagnoses of either autism or Asperger's Syndrome. Could it be that he has a deep emotional investment in his own Aspergers' diagnosis which, acquired in adulthood, gave him the explanation he may have needed for the social difficulties he experienced growing up? According to his website, one can imagine that his early life would have been made far easier for him if what he would undoubtedly regard as his different neurology had been recognised, understood, and accommodated in childhood.

http://www.angelfire.com/in/AspergerArtforms/casehist.html

I suggest David Andrews' experience of what appear to be a series of misdiagnoses and prescribed psychiatric drugs forced upon him in adolescence with the threat of institutionalisation hanging over his head might lie behind his motivation to become an activist in the movement to change how society regards and treats people with mental health problems and neurological disorders, to get them to view the minds of the outcast members of society as neurologically different and not defective. The lives of those whom society labels: weirdos, strange coves, space cadets, fools and idiots would be vastly improved if the name-calling was dropped and they were to be valued for who they are.

As the parent of a young man with extreme difficulties, especially in the social realm, I think the primary aim of the movement - acceptance - is laudable, no one should be outcast from society. But I do have a problem with it for several reasons, one of which is that my son's condition and the prospect of a lifetime of dependency and ostracism from society could have been avoided if only medical professionals had taken notice of the reactions that he had had to all the vaccines he received, starting with the first. Instead of taking them seriously, they were repeatedly ignored. I consented to further vaccines simply because I trusted doctors, and rationalised that they wouldn't give him another unless they knew for certain that they were absolutely safe for him. I was wrong. Little did I know that they had a quota to fulfil in order to earn their bonus, and at the forefront of their minds was more likely than not to be the protection of the herd, not my child. I cannot embrace a movement whose members openly and vociferously support and defend a medical procedure known to cause permanent neurological damage to the smallest and most vulnerable members of society, and who bully unmercifully the parents who blame vaccination for their child's regression.

The Autistic Liberation Front or the Neurodiversity Movement only started to get off the ground after the publication of Dr Wakefield's paper associating MMR and autism in 1998, and the American Academy of Pediatrics (AAP) and the Public Health Service (PHS) called for the removal of thimerosal from vaccines in July 1999 in response to concerns that babies and small children were being injected with too much mercury which might be causing the observed increase in neurodevelopmental problems.

Perhaps as David Andrews questions my son's diagnosis, he wouldn't mind discussing his involvement with Simon-Baron Cohen's study "Can Asperger Syndrome Be Diagnosed at 26 Months Old? A Genetic High-Risk Single-Case Study". I would be most interested in hearing his opinion as to why the child in this study was diagnosed with Asperger's Syndrome at 26 months "on the basis of both the Autism Diagnostic Interview ? Revised (Re-written by Michael Rutter, Ann LeCouteur, and Catherine Lord and published in 2003 for the purpose of diagnosing younger children) and Autism Diagnostic Observation Schedule scores, as well as clinical interview", and not the DSM-IV. This case study of only ONE, single child is supposed to have provided the evidence that Asperger's Syndrome is genetic.

http://www.cbcd.bbk.ac.uk/people/scientificstaff/mark/PDFs/Can_Asberger_Syndrome

Since the paper surfaced, several toddlers that I am aware of, some as young as eighteen months, have been given an Asperger's Syndrome diagnosis which until the above study was conducted, with the support of the Medical Research Council starting I believe in 1998/99 before the child was born, was rarely detected or diagnosed before seven years of age, and the average age for diagnosis was eleven. In fact the autism specialist we consulted who initially attributed my son's autistic behaviours, social problems, and cognitive defects to his severe language disorder, wrote some time after our appointment that we needed to wait until the clinical picture became clear, and a reassessment would be necessary at a later date to be certain.

It might surprise David Andrews that my son was re-labelled with Asperger's in his mid-teens, despite a score of only 28/50 on Simon-Baron Cohen's Autism Spectrum Quotient Test which appeared online in 2001. Although my son achieved an above average score, according to the test, "eighty percent of those diagnosed with autism or a related disorder scored 32 or higher" "and many who score above 32 and even meet the diagnostic criteria for mild autism or Asperger's report no difficulty functioning in their everyday lives". What exactly is the diagnostic criteria for mild autism or mild Asperger's? Do the experts even know what they are doing? Especially to disabled people on the spectrum?

http://www.wired.com/wired/archive/9.12/aqtest.html

Perhaps David Andrews could also explain why in 1999 a group of adults with high-functioning autism and Asperger's diagnoses, and another who was self-diagnosed, according to her own admission in her book published in the same year, discussed with Baron-Cohen whether or not Asperger's Syndrome/High Functioning Autism is necessarily a disability, the subject of which was raised by Andrews himself.

http://www.larry-arnold.net/Neurodiversity/Mission/disability.htm

In my opinion David Andrews might possibly have competing interests in this subject.

Competing interests: My son regressed after vaccines. He has never received the MMR.

Readers should be aware of some of the findings of this document titled - June 1999: Report of the working party on MMR vaccine. 1

The Working Party looked specifically at the broader cohort of children, outside of Wakefield's initial case review of 12. These children were the ones clearly as seen at risk by their parents.

"The Working Party considered the diagnostic criteria which should be used for autism, pervasive developmental disorder (PDD), developmental delay, encephalitis, different types of inflammatory bowel disease and other types of bowel disorder."1

The report found an extremely good accuracy for this cohort of children clearly refuting the reporting by Brian Deer.

Confirmation of diagnosis of Autism/PDD.

"Of the 95 cases of reported autism evaluated, the diagnosis was considered confirmed as autism/PDD in 81, possible in 11 and not confirmed in 3. The three unconfirmed reports were all considered to be cases of global developmental delay."

It clearly demonstrates that the concerns were real, these children had autism.

It clearly demonstrates the accuracy of the parents' assessment in taking their children to Royal Free.

It shows clearly that a caring and loving family should not be so easily dismissed when it comes to their knowledge and understanding of their children.

This is a profound and simple lesson for Brian Deer and the BMJ editorial staff.

Will they continue to question the accuracy of the parent reports on the onset of symptoms of autism in relation to immunisation as well ?

regards

1. June 1999: Report of the working party on MMR vaccine A full transcript can be found at http://briandeer.com/wakefield/csm-report.htm

Competing interests: Father of ASD son

As long as the aetiology of Infantile Autism is not generally accepted, although it has been published years ago, hypotheses flourish. Usually age of onset is set at before three years of age. However, infantile autism occurs in the 2nd adaptive brain event at around 6-7mo caused by a pruning of Supplementary Motor Area (SMA), the centre in Medial Frontal Lobe System connecting Hippocampus and Cingulum, in the synaptogenesis at 6-7mo in some very slowly maturing infants. This is the time we usually learn the Delayed Response Function which is exactly what the infants with autism lack. An inability to conscious acts, to plan, predict according to storage of information (memory): A PSYCHOSIS.

It has to be added that an acutely psychotic adult has similarly absent-deficient activity in the SMA and in Cerebellum as infantile autism which is a chronic psychosis. This implies a temporary macrocephaly associated with temporary deficient Purkinje cell activity. It usually ends with microcephaly at puberty in the most severely affected. Persistent defect of the Delayed Response Function, implies a deficient social brain in infantile autism. All their various symptoms are explained by this persistent deficiency which occurs in the 2nd adaptive brain event in infancy.

Following the first adaptive brain event at birth, we have Asperger Syndrome due to deficient "brain food" in pregnancy, affecting our only two areas with continuous neurogenesis and an increased need for "brain food" Olfactory Bulb and Hippocampus. Routine testing of Olfaction in infancy as well as in the elderly is recommended as it is a first symptom of deficiency in "brain food" also in neurodegenerative disorders.

As regards the MMR scepticism related to content of methyl mercury in the preservative, this similarly to the arguments against eating fish in pregnancy is irrelevant and unfortunate. Studies comparing offspring of mothers eating fish with offspring of pregnancies with no fish-eating invariably favour the fish-eating offspring. Infantile Autism and Asperger Syndrome are both markedly increasing in Europe but particularly in the USA, revealing deficient brain food in pregnancy and infancy. It has been estimated that we eat only some 20% of brain food compared to 100yrs ago (polyunsaturated fatty acids, PUFA; Omega-3. We better start eating more fish, knowing that "toxic effects" are irrelevant. What is important in brain development which is multifactorially inherited is to be aware of the important role of epigenetic factors for optimal brain development and function. Infantile Autism and Asperger Syndrome are avoidable brain disorders with optimal brain function. Early fast development is advantageous at birth with minimal mortality in birth weights some 500g above the mean. Similarly in infancy.

Early fast development is advantageous as is also the common view. Persistent defects might arise in very slowly developing infants such as following a serious infection.

Adversity invariably delays rate of growth and maturational and might thus contribute to a development of autism.

For further reference my articles "Infantile autism" and "What is a psychosis and where is it located?" may be provided.

Letten F. Saugstad, Professor University of Oslo

Private address: Behrens gate 5, 0257 Oslo

Competing interests: None declared

1) Gonzalez, L. et al., Endoscopic and Histological Characteristics of the Digestive Mucosa in Autistic Children with gastro-Intestinal Symptoms. Arch Venez Pueric Pediatr, 2005;69:19-25.

2) Balzola, F., et al., Panenteric IBD-like disease in a patient with regressive autism shown for the first time by wireless capsule enteroscopy: Another piece in the jig-saw of the gut-brain syndrome? American Journal of Gastroenterology, 2005. 100(4): p. 979- 981.

3) Balzola F et al . Autistic enterocolitis: confirmation of a new inflammatory bowel disease in an Italian cohort of patients. Gastroenterology 2005;128(Suppl. 2);A-303.

4) Krigsman A, Boris M, Goldblatt A, Stott C. Clinical Presentation and Histologic Findings at Ileocolonoscopy in Children with Autistic Spectrum Disorder and Chronic Gastrointestinal Symptoms. Autism Insights. 2009;1:1-11.

5) Horvath K., Papadimitriou J.C., Rabsztyn A., Drachenberg C., Tildon J.T. 1999. Gastrointestinal abnormalities in children with autism. J. Pediatrics 135: 559-563.

6) Sabra S, Bellanti JA, Colon AR. Ileal lymphoid hyperplasia, non- specific colitis and pervasive developmental disorder in children. The Lancet 1998;352:234-5.

7) Sabra A, Hartman D, Zeligs BJ et al., Linkage of ileal-lymphoid- nodular hyperplasia (ILNH), food allergy and CNS developmental abnormalities: evidence for a non-IgE association, Ann Allergy Asthma Immunol, 1999;82:8

8) Galiatsatos P, Gologan A, Lamoureux E, Autistic enterocolitis: Fact or fiction? Can J Gastroenterol. 2009:23:95-98

9) Jarocka-Cyrta et al. Brief report: eosinophilic esophagitis as a cause of feeding problems in an autistic boy. The first reported case.J. Aut. Dev. Disord. Online July 10, 2010

The following articles support the importance of recognizing and treating gastrointestinal symptoms in autistic children:

1) Buie T, et al. Pediatrics. 2010 Jan;125 Suppl 1:S19-29. Recommendations for evaluation and treatment of common gastrointestinal problems in children with ASDs.

2) Buie T, et al. Pediatrics. 2010 Jan;125 Suppl 1:S1-18. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report.

The following peer-reviewed papers provide further support for gastrointestinal disturbances involving the immune system in autism.

1) Jyonouchi H., Sun S., Lee H. 2001. Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression. J. Neuroimmunol. 120(1-2):170-9

2) Jyonouchi H, Geng L, Ruby A, Zimmerman-Bier B. Dysregulated Innate Immune Responses in Young Children with Autism Spectrum Disorders: Their Relationship to Gastrointestinal Symptoms and Dietary Intervention. Neuropsychobiology. 2005;28:5177-85

3) Jyonouchi H, Geng L, Ruby A, Reddy C, Zimmerman-Bier B. Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders. J Pediatr.2005;146(5):605-10.

4) Jyonouchi H, Sun S, Itokazu N. Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorder. Neuropsychobiology. 2002;46(2):76-84.

5) Vojdani A, O'Bryan T, Green JA, McCandless J, Woeller KN, Vojdani E, Nourian AA, Cooper EL. Immune response to dietary proteins, gliadin and cerebellar peptides in children with autism. Nutr. Neurosci. 2004;7:151- 61.

6) Whiteley P, Haracopos D, Knivsberg AM, Reichelt KL, Parlar S, Jacobsen J, Seim A, Pedersen L, Schondel M, Shattock P. The ScanBrit randomised, controlled, single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders. Nutr Neurosci. 2010;13(2):87-100.

7) Knivsberg AM, Reichelt KL, H?ien T, N?dland M. A randomised, controlled study of dietary intervention in autistic syndromes. Nutr Neurosci. 2002;5(4):251-61.

8) Balzola F, et al. Beneficial behavioural effects of IBD therapy and gluten/casein-free diet in an Italian cohort of patients with autistic enterocolitis followed over one year. Gastroenterology 2008;4:S1364.

9) Valicenti-McDermott M., McVicar K., Rapin I., et al., Frequency of Gastrointestinal Symptoms in Children with Autistic Spectrum Disorders and Association with Family History of Autoimmune Disease. Developmental and Behavioral Pediatrics. 2006;27:128-136

10) Chen B, Girgis S, El-Matary W. Childhood Autism and Eosinophilic Colitis. Digestion 2010;18:127-129

11) Sandler R, Finegold SM., Bolte ER., et al. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol. 2000;15:429-435

Competing interests: None declared

Has Andrews considered this:-

Autism is mentioned in the paper because the child subjects had been diagnosed with autism. It would seem rather odd were their developmental diagnoses not mentioned, especially when their families were of the mind that their autism developed in association with their GI problems.

I believe that Deers' statistics are faulty - see my letter below for the evidence or read the original paper and Deer's summation of histology, lab and endoscopy along with the parental anecdote and Royal Free physicians investigations for each child and you ought to reach my conclusion that Deer has failed to recognise the necessity to include all evidence, direct, material, circumstantial and expert witness (parents). Regressive autism in the context of the Wakefield paper is, as the LNH special diagnosis, essentially a novel diagnosis that the Royal Free Team appear to have become accustomed to only through their investigations of the twelve children just as the histology was novel as the disorder was novel; the nearset possible diagnostic measure may have been childhood disintegratve disorder just as the nearest possible diagnostic measures provided by the histology had to approximate to what was known, not novel. That is why the endoscopies, lab work, family and medical input were so necessary along with the additional investigations by Royal Free paediatric, psychiatric and GI physicians - novel findings require novel discussions and novel summation. This seems to be lost on Deer, Andrews, and many other observers.

Competing interests: None declared

As the author of the retabulation that has caused a flurry of letter writing I should perhaps make the message presented clearer to all.

I read Rutter's work as part of my major in Abnormal Psychology at University in 1990 and as I recall at that time the diagnosis and identification of a child who was Autistic was a rare event.

As I said in my original rapid response times have changed dramatically in all areas of ASD.

We are standing on shifting sands what could be said in 1990 changed significantly in 1998, now 13 years later in 2011 their is a recognition that those boundaries between Autism Spectrum Disorders have become very blurred.

DSM V revision recognises this and I believe is being readjusted to suit this, though of course it has not been finalised.

Thus when people talk of absolutes when it comes to ASD and its many facets they should be cautious in both retrograde analysis and future prediction.

Fitting ASD kids into boxes is a herculean task ... the one helpful protocol I have found in education is to address the needs of that individual that stands in front of you.

Competing interests: Father ASD son

In his lengthy rapid response (11 January 2011), David Andrews, Finnish autism professional, appears outraged - and not a little confused - at those amateurs unable to distinguish between Hellers disease (CDD) and an autistic spectrum disorder. However, confusion also reigns supreme amongst established British professionals like Professor Sir Michael Rutter. In his 1985 book, 'Infantile Autism and other Pervasive Development Disorders in Child and Adult Psychiatry', Rutter wrote,

"The clinical picture [in Childhood Disintegrative Disorder CDD] after the phase of regression is often somewhat similar to autism and the differentiation may be difficult, if not impossible, in cases with an onset before 30 months."

Some years later Sir Michael appeared as a key prosecution witness at the GMC hearing into the crimes of the Royal Free Three. During the proceedings Rutter was asked,

"In embarking on a study of children with behavioural disorder, would [he] expect a distinction between CDD and autism to be made." The reply was, "yes". And Rutter continued, "and the literature would support drawing a clear distinction at the time [1996]." [1]

Eh?

[1] Andrew Wakefield, 'Callous Disregard: Autism and Vaccines - The Truth Behind the Tragedy', Skyhorse Publishing, New York 2010. p135.

Competing interests: None declared

From the day my son was diagnosed I saw the professionals trying to tick boxes, every question had to be answered - yes or no, but sometimes human frailty isn't that simple. So often even now, the professionals miss the point in their attempts to make us fit a particular criteria. The human body is complicated and the brain even more so. The greatest skill of the physician in the future will be to fully understand the interaction of the two. It is the scenario of regression that is important and the 'cause' of the 'brain damage' that should be addressed. If every baby book now included a chapter on 'Infant regression' that started with the words - There is a 1 in 64 chance that your child will regress to the point where you will be a Carer for the rest of your life - it would be considered shocking, but this is the scenario that has occurred in homes all over the world, in the last 15-20 years. Brian Deer and the BMJ can argue about the details of the Lancet Paper but they cannot deny that children like my son exist. When will they be investigated beyond the box ticking?

Competing interests: Mother of son with regressive autism

David N. Andrews,

Thank you very much for going to the trouble of reviewing the little of my son's history that I provided, and suggesting that his correct diagnosis might be Childhood Disintegrative Disorder.

I first came across Heller's Syndrome/Childhood Disintegrative Disorder in 1999, some years after my son's diagnoses. He certainly met the criteria, but none of the specialists involved in evaluating my son over the years diagnosed him with it. Why was that? Perhaps they didn't ask the right questions, or maybe they didn't think that my son was old enough for his development to have disintegrated, seeing as the condition usually occurs between 3 and 4 years of age, and, as I'm sure you already know, it has always been considered such a rare disorder, affecting approximately 1 in 100,000 children, it may not have even occurred to them that a patient of theirs might have it. I think we have to bear in mind that they were evaluating him on his presentation at the time of the consultation, not at the time of his regression at age two. which was insidious over a period of months. Losing skills and language was not a major focus for any of us at the time of our consultation, what was uppermost in our minds was how to help him.

Tell me please:

1) How would this re-classification to another Autism Spectrum Disorder have benefited my son, and how would it benefit him now as an adult?

2) How would it have altered his treatment? (No treatment was prescribed).

3) Do adults with CDD in childhood carry their diagnosis with them throughout their lifetime, or are they reclassified later, depending on their presentation?

And..

4) Currently, are services made available to children and adults labelled with CDD, or is help only available for children with autism?

"Heller Syndrome was the original PDD listed in the research that Wakefield had been doing". Yes, Wakefield discussed Heller's Disease on page 640 of THE LANCET * Vol 351 * February 28, 1998, but "Heller Syndrome" to my knowledge is not mentioned in the DSM -IV, nor is it a PDD, but CDD is. And CDD is classified as a PDD, in other words an Autism Spectrum Disorder.

As a psychologist, if you were presented with a room full of young children who'd been diagnosed with either CDD or Autistic Disorder, would you be able to identify the ones who had regressed? How exactly would you know which was which?

I feel sure you will be familiar with Catherine Maurice's book Let Me Hear Your Voice (published 1994). Both of her children regressed but they were given autism diagnoses. Charlotte Moore's children also regressed, and, as she tells us in her book George and Sam (published 2005), that within two or three years, one of her son's had his Asperger's diagnosis changed to Autistic Disorder. Presumably you would consider this re- diagnosis to be impossible. In your view, these four children with regression should have been diagnosed with CDD. Correct?

You are suggesting that the DSM and ICD are the only available criteria for diagnosis, that they are always used, and that they are just as infallible as blood tests. But, and I'm certain that you will already know this, there are other sets of criteria such as Gillberg and Gillberg and Szatmari which some psychologists prefer to use. What one psychologist might diagnose as Autistic Disorder, another might diagnose Aspergers Syndrome because of the child's functioning level at the time of his or her presentation.

Diagnosing developmentally regressed children with autism or Asperger's Syndrome is not unusual, and neither is re-classifying them. Psychologists and psychiatrists give opinions, not diagnoses that are set in concrete. Brian Deer especially should know that.

What is important to realise is that once children are burdened with the autism label, as I mentioned before, every medical condition and behaviour they exhibit is blamed on "the autism" and no one will medically examine them. Covering their ears, for example, at what would to us be considered normal background sounds - something as seemingly innocuous as music for instance; poor sleeping habits; tactile sensitivity; severe tantrums; diarrhoea; leaning their bellies on furniture, and vomiting. Psychologists seem to regard these as normal for an autistic child, and being specialists in their field, who is going to question their expertise? Only, it seems, Dr Andrew Wakefield and his team at the Royal Free who were prepared to put the psychiatric diagnosis aside, investigate the physical manifestations of disease, and examine the bowels of children with bloating, diarrhoea and abdominal pain.

When I wrote, "I am certain that what most parents of a child with regressive-type autism want to know is what happened to their child's brain. I certainly do", your response was: "Who wouldn't want to know what was going on? "

There are all kinds of people who don't want to know what's going on. Those that think that it is better to turn a blind eye to the children with brain injury or developmental regression after vaccine reactions, than to publicly acknowledge that vaccines can and do permanently and severely damage children. They believe that a few casualties of vaccination are a small price to pay for protection for everyone else from what are called vaccine-preventable diseases. Because without vaccination, they believe, many more children would be brain-injured or die. Acknowledging to the general public that there are hundreds or thousands more babies and children than the '1 in a million' they claim are damaged by vaccination would kill the programme. They believe that a great many more children's lives are at stake.

Competing interests: My son regressed after vaccines. He has never received the MMR.

The article starts with "Clear evidence of falsification of data should now close the door on this damaging vaccine scare."

How can one bad study disprove a theory? As an engineer/tec and one who has spent days in labs doing testing there seems no logic to that beginning statement. Every inventor and researcher has failed many times before proving their point. Louis Pasteur got Penicillin from an apparent failure. What does one lying witness prove? Usually in science you must prove something true or false.

Regards, Dale Dupont

Competing interests: I have studied into autism and wrote one article http://www.associatedcontent.com/article/5602710/autisms_core.html?

Dear Sir,

In response to Professors Awofeso and Rammohans' plea for re-thinking the 2000 - 2008 global measles morbidity and mortality data, to do so is to enter as big a minefield as analysing the recent downgrade by CDC, of the annual flu deaths in America, which has arbitrarily been reduced from 36,000 to 24,000 death, by the use of a pen. Sorry - computer mouse.

The first African measles data "landmine" to step on is the fact that in 2000, if measles looked like measles, it was called "measles". Based on guessing the diagnosis from appearance, Africa's measles data was... "estimated".

Starting in 2000, WHO implemented a huge network of laboratories whose task was to take these "guessed at" measles cases, and test them to see if what was "thought" to be measles, was actually measles.

So if for instance, you looked at page 14 in the WHO 2006 "Afro Measles Surveillance Feedback Bulletin, January 2006" (1) you will see that of the 14,185 cases reported in 2006, after blood testing, 9,764 were "discarded", because the "measles" wasn't measles at all. That's an immediate 69% drop in cases, because they are no longer relying on doctor's eyes.

This will also have immediately have affected the percentage death rate drop as well.

But if you take the WHO data on page 2 of the same document, out of 14,185 cases, 3,257 were accepted leaving a balance of 10,928 discarded, so that equals 77% which were NOT measles after blood testing.

So the question has to be asked about consistency in measles death rate data, as well as case rate. You can apply one standard to one thing, another to another, which will result in utter confusion.

The same thing happened in the UK when saliva testing was introduced. Suddenly, 98% of what was visually thought to have been unmistakable classical measles cases, was - with the stroke of a laboratory diagnostic test, allocated to a raft of other viruses. Which automatically gives your graph a nice downwards crash.

Whereas some would say that commonsense dictates that you shouldn't compare "look-see" data with "laboratory confirmations" this is exactly what the medical system does, because it's suits the message which is that the measles vaccine caused the decrease. Yet laboratory-confirmed cases is a far cry from the crystal-ball gazing that went on up to 2000. By saying there was a 90% decline since then, they are comparing 'apples' with 'army jeeps'.

While it boggles the mind that Africa can fund and test even 20% of actual measles cases, let alone 100%, let's assume that all cases of measles are tested, and WHO figures are accurate. If this is the case, then the WHO claim of 90% decrease is unscientific on the fundamental grounds of the non admission that the change in diagnostic criteria created most of the decline in the first place.

If Professors Awofeso and Rammohan are right, and much of the measles cases aren't even reported, then who knows if there has really been a decline at all?

If we took the pre-2000 measles data from Africa, and automatically removed 77% of those cases on the presumption that this is roughly the percentage testing appears to eliminate, then the real meases decrease in Africa, might only be 13%, not 90%. Which still doesn't allow for under- reporting...

The latest AFRO report once again shows that the majority of measles cases are dismissed as a result of laboratory results.

It would be unlike that African measles cases/deaths data will be revised upwards or accurately analysed, (for that would indicate EPI failure) unless good reasons can be found - which don't undermine current EPI vaccination practice - to justify pushing MORE measles vaccine than is already delivered to Africa.

Hilary Butler.

(1) WHO January 2006 AFRO data: http://www.google.co.nz/url?sa=t&source=web&cd=2&ved=0CBwQFjAB&url=http%3A%2F%2Fwww.afro.who.int%2Findex.php%3Foption%3Dcom_docman%26task%3Ddoc_download%26gid%3D3653&rct=j&q=Afro%20Measles%20Surveillance%20Feedback%20Bulletin.%20January%202006&ei=huYsTdWZH4 -asAPrhcnVBg&usg=AFQjCNFC1G6pWMLnT_KB8LXVLE-3JKjn2A

(It's probably easier to google the titles.)

Competing interests: I love figuring out bad science through the ages...

It seems rather odd that the latest campaign to discredit Andrew Wakefield happened at a time he was attending an international meeting in Montego Bay, Jamaica Jan. 3-7, 2011 to discuss current vaccine science and policy safety concerns. Delegates from around the world included senior scientists and physicians, editors of scientific journals, experts in vaccine regulation, social science and health policy, consumer child health advocates, legal experts and members of the media.

http://www.vaccinesafetyconference.com/index.html

Among the scientists present was Dr Yehuda Shoenfeld, the head of the Department of Medicine at the Tel Aviv University since 1984 (age 36). Has founded and is heading the Center for Autoimmune Diseases since 1985 - at the largest hospital in Israel- the Sheba Medical Center. He has published over 1600 papers in journals such as New Eng J Med, Nature, Lancet, Proc Nat Acad Scie, J Clin Invest, J Immunol, Blood, FASEB, J Exp Med, Circulation, Cancer and others. His articles have had over 20,000 citations until 2009. He has authored and edited 25 books, some of which became cornerstones in science and clinical practice, such as "The Mosaic of Autoimmunity", "Infections and Autoimmunity", the textbook "Autoantibodies" and "Diagnostic Criteria of Autoimmune Diseases", all of which were published by Elsevier and sold by thousands.

He is on the editorial board of 43 journals in the field of Rheumatology, and Autoimmunity and is the founder and the editor of the IMAJ (Israel Medical Association Journal) the representative journal of Science and Medicine in the English language in Israel. Shoenfeld is also the founder and Editor of the "Autoimmunity Reviews" (Elsevier) (Impact factor 6.2). He has written over three hundred chapters in different books.

Shoenfeld obviously felt that Andrew Wakefield deserved to be heard. I wonder, what scientific credentials does Brian Deer hold that the world should listen to him?

At a recent interview, Richard Deth, Professor of Pharmacology in the Department of Pharmaceutical Sciences at Northeastern University, who was also at the conference made the following statement:

http://www.northeastern.edu/news/stories/2011/01/deth.html

"Wakefield's identification of gastrointestinal inflammation in autism will remain an important scientific contribution. The magnitude of the effort to discredit him betrays a strong fear that his suggestion of a link to vaccination may be correct. It amounts to a public pillorying that frightens others from investigating this controversial but important issue."

I wonder, whatever happened to true science? One not driven by dogmatic preconceptions but based on rigorous evaluation of scientific evidence. Food for thought.

Competing interests: None declared

David Andrews has failed to make a point. The term "autism" is also widely current in the US where DSM diagnostic criteria are commonly used, as well as by Dr Harvey and Berelowitz in the Wakefield paper.

Retrospectively, one could say that cases of regressive autism are now very common, or even the norm, but that does not make them Heller's disease or disintegrative psychosis. You could see actually that the authors may have been struggling with the concept of regressive autism which as Andrews admits is not covered by the diagnostic criteria. And if Andrew does not in 2011 understand that regressive autism is a frequent experience of families he may not be listening adequately to the parents. I can certainly say that back in 1995 when our son was diagnosed the clinicians were quite uninterested in the regressive features of his history.

But once again I must protest that histories were taken by John Walker-Smith: the neurological diagnoses were made by Peter Harvey and Mark Berelowitz, and though some of these gentleman may have distanced themselves long ago from the MMR hypothesis, they have never repudiated their own data. So, I ask how it was possible for Wakefield to have fabricated it?

Competing interests: Autistic son

First I must apologise I am not an academic nor have pretensions to be one I am a simple father with a son with ASD. Therefore my essay may not follow the essential referencing and format required of an academic journal and for this I apologise.

The Central Plank

There is always a central plank or theme to any discussion. In this particular debate it would be said to be the "Link of the MMR Vaccine to Autism".

I would like to draw to the attention of the reader to some current research in the field of immunology that may help clarify some issues in the MMR vaccine debate.

I believe both Fiona Godlee Editor and Brian Deer in recent days both commented that there has not been any evidence of a link between the MMR Vaccine and Autism.

"Over the following decade, epidemiological studies consistently found no evidence of a link between the MMR vaccine and autism."1

and from Brian Deer.com (http://briandeer.com/mmr/lancet-summary.htm)

"Deer (who in April 2006 reported the first British measles death in 14 years) took no view on whether vaccines may or may not cause autism, but never found any scientific material which repeated the Lancet findings. Although all kinds of children suffer from digestive issues, he learnt of a mass of authoritative research which overwhelmingly rebutted Wakefield's claims. "Specifically, numerous studies have refuted Andrew Wakefield's theory that MMR vaccine is linked to bowel disorders and autism," was how the American Academy of Pediatrics summarised the position in an August 2009 statement to NBC News for a Dateline programme which featured both Wakefield and Deer. "Every aspect of Dr Wakefield's theory has been disproven." "1a

To my mind the following studies do represent just such a link and perhaps the tool of epidemiology was the wrong instrument to precisely uncover that association.

This is taken from the work of J E Libbey et al Department of Neurology, University of Utah.

"Biological assays lend support to the association between measles virus or MMR and autism whereas epidemiologic studies show no association between MMR and autism.Further research is needed to clarify both the mechanisms whereby viral infection early in development may lead to autism and the possible involvement of the MMR vaccine in the development of autism."2

It not only identifies the association between MMR and Autism. But identifies a specific research tool eg biological assays as a more precise instrument in which to do so.

Vijendra K. Singh et al had this to say in his 2001 study.

"Furthermore, over 90% of MMR antibody-positive autistic sera were also positive for MBP autoantibodies, suggesting a strong association between MMR and CNS autoimmunity in autism. Stemming from this evidence, we suggest that an inappropriate antibody response to MMR, specifically the measles component thereof, might be related to pathogenesis of autism."3

This second study also identifies MMR as part of the development of autism.

Dr Zimmerman wrote the following in his biographical page at the Kennedy Kreiger Institute where he is Pediatric Neurologist and Director of Medical Research at the Center for Autism and Related Disorders Baltimore. He is also an Associate Professor of Neurology and Psychiatry at the Johns Hopkins University School of Medicine.

"Dr. Zimmerman and colleagues recently found that rheumatoid arthritis and other autoimmune disorders are more common than expected in the families of children with autism. This leads to speculation that autoimmune disorders might be a sign of genetic susceptibility to Autism. Such a predisposition may act through genes associated with the human lymphocyte antigens, which commonly have specific associations with autoimmune disorders. These genetic effects most likely begin before birth and might be modified by the mother's, as well as the father's, genes. This may lead to disruption in normal development of the immune, as well as the nervous, systems in the fetus. It is hoped that a better understanding of the links between the developing immune and nervous systems will eventually improve the treatment of persons with autism." 4

Further V K Singh and R L Jensen Department of Biology and Biotechnology Center, Utah State University said the following in their study.

"Virus-induced autoimmunity may play a causal role in autism. To examine the etiologic link of viruses in this brain disorder, we conducted a serologic study of measles virus, mumps virus, and rubella virus... ...Thus autistic children have a hyperimmune response to measles virus, which in the absence of a wild type of measles infection might be a sign of an abnormal immune reaction to the vaccine strain or virus reactivation."5

Further refernce in regards to MMR / Autism in "Possible immunological disorders in autism: concomitant autoimmunity and immune tolerance." Kawashti MI et al

"It is concluded that, autoimmune response to dietary proteins and deficient immune response to measles, mumps and rubella vaccine antigens might be associated with autism, as a leading cause or a resulting event. Further research is needed to confirm these findings."6

In regards to Ethyl Mercury often portrayed as a villain in the MMR Vaccine debate. I was able to find this evidence.

"Similar to many complex autoimmune diseases, genetic and environmental factors including diet, infection and xenobiotics play a critical role in the development of autism. In this study, we postulated that infectious agent antigens such as streptokinase, dietary peptides (gliadin and casein) and ethyl mercury (xenobiotic) bind to different lymphocyte receptors and tissue enzyme (DPP IV or CD26)."7

The conclusion from A Vojdani Comparative Immunology, Dept. Neurobiology, UCLA Medical Center.

"In conclusion, this study is apparently the first to demonstrate that dietary peptides, bacterial toxins and xenobiotics bind to lymphocyte receptors and/or tissue enzymes, resulting in autoimmune reaction in children with autism."8

To my mind it is surprising that more research wasn't developed particularly in the light of all we knew about the aetiology of Autism and Congenital Rubella Sndrome.

Perhaps I can best some up by using some of the participants own words.

"There are hard lessons for many in this highly damaging saga...."9

1.9 BMJ 2011; 342:c7452 Editorial Wakefield's article linking MMR vaccine and autism was fraudulent Fiona Godlee, editor in chief, Jane Smith, deputy editor, Harvey Marcovitch, associate editor. 2011

1a Deer, Brian Nailed: Dr Andrew Wakefield and the MMR - autism fraud undated Web page at Brian Deer.com

2 Pardo CA, Vargas DL, Zimmerman AW. Autistic disorder and viral infections - Journal of Neurovirology 2005 Immunity, neuroglia and neuroinflammation in autism.

3.Vijendra K. Singh, Sheren X. Lin, Elizabeth Newell and Courtney Nelson Journal of Biomedical Science Volume 9, Number 4, 359-364, DOI: 10.1007/BF02256592 Abnormal measles-mumps-rubella antibodies and CNS autoimmunity in children with autism 2001

4.Zimmerman Andrew http://www.kennedykrieger.org/kki_staff.jsp?pid=1068 Staff Biography

5.Singh VK, Jensen RL.Pediatr Neurol. 2003 Apr;28(4):292-4. Elevated levels of measles antibodies in children with autism.

6. Kawashti MI, Amin OR, Rowehy NG Possible immunological disorders in autism: concomitant autoimmunity and immune tolerance. Egypt J Immunol. 2006;13(1):99-104.

7. 8. Vojdani A, Pangborn JB, Vojdani E, Cooper EL.Int J Immunopathol Pharmacol. 2003 Sep-Dec;16(3):189-99. Infections, toxic chemicals and dietary peptides binding to lymphocyte receptors and tissue enzymes are major instigators of autoimmunity in autism.

Competing interests: Autistic Son

In February 1998, Dr Richard Horton, editor of The Lancet, published a peer reviewed case series report written by 13 highly qualified medical researchers entitled, 'Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children'. In 2003 Horton wrote,

"The MMR vaccine paper was published not because peer review indicated that the findings were true - peer review can never prove truth, only indicate acceptability to a few experts, as was indeed the case with Wakefield's findings - but because the issue raised was so important for public health and so in need of urgent verification that not to publish with appropriate caveats would, in my view, have been an outrageous act of censorship." [1]

For nearly three years the GMC carried out a forensic dissection in public: even the GMC found no evidence that the Lancet paper was a fraud. Dr Andrew Wakefield FRCS, FRCPath is a fraud because journalist Brian Deer says so. BMJ editors, Drs Godlee, Smith and Marcovitch know that the paper was fraudulent because a journalist has said it is - a freelance journalist with absolutely no medical or scientific credential.

Wakefield ... there is a problem! With no reasonable doubt, there is fear and loathing in Las Vegas and well beyond. Despite repeatedly virulent attack he is still breathing: by rights Andrew Wakefield should be down and out in London, Paris and Texas too. Will overkill make the problem go away?

[1] MMR: The Lancet Fiasco. Richard Horton glorifies Wakefield, with "no regrets" over discredited MMR paper. http://briandeer.com/mmr/horton- wakefield.htm

Competing interests: None declared

"I question that a professional such as Andrews should enter into published discussion without checking the text of study and with an apparently revisionist historical agenda."

I have the paper. I have read the paper. Autism is mentioned rather a lot in the text of the paper! Maybe you yourself didn't read the paper. I know that I did.

"I believe this illustrates how farcical the pillorying of Wakefield has become."

Believe what you like. But don't be preaching it at us as if it is absolute truth. It isn't.

Looking at the statistics presented by Deer, it is clear that Wakefield was vastly overstating something: only one child out of the twelve that he cherry picked for the paper had a clear 'regressive autism'* thing going on. Those out of the rest who were not developing typically were already on a developmental trajectory that differed from the ones that most people would follow.

As for revisionism... hmmm, well... it seems that - when something comes out that is at odds with what you prefer to believe - you accuse the messenger of being 'revisionist' instead of actually taking a critical look at your own understanding of the situation to see if - maybe, just maybe - you were wrong! That is how you reduce the cognitive dissonance: by rejection of new information out of hand rather than take on the more effortful task of checking your assumptions. Such a way of dealing with a dissenting view-point is lazy, uncritical and basically faulty: hence your failure to learn anything from the whole Wakefield scandal. Not much point in discussing anything with you because you have a tendency to 'go revisionist' on what others whose view oppose your views say (whilst decrying then for being 'revisionistic' themselves; can you not see the hypocrisy in doing that? Or do you reduce the cognitive dissonance on that one by denying what you clearly do?).

* 'regressve autism' is not actually mentioned in either ICD 10 or DSM IV (in either of its versions): what is mentioned is something Wakefield picks up on in the paper... childhod disintegrative syndrome, also known as Heller syndrome or dementia infantalis. This is interesting in that Wakefield was using this paper to claim a link between MMR and autism: he was claiming that the children in the study became autistic after their MMR vaccines. And it now seems that most of them were already on that developmental trajectory prior to inclusion in the study. Wakefield says:

"In some cases the onset and course of behavioural regression was precipitous, with children losing all communication skills over a few weeks to months. This regression is consistent with a disintegrative psychosis (Heller's disease), which typically occurs when normally developing children show striking behaviour changes and developmental regression, commonly in association with some loss of coordination and bowel or bladder function. Disintegrative psychosis is typically described as occurring in children after at least 2-3 years of apparently normal development."

This is true. But this is not autism: it is a disintegrative disorder in childhood, somewhat akin to dementia in older adults. Had there been any truth in the idea that all these children's behavioural semiologies began after they were vaccinated with the MMR vaccine, then this disintegrative disorder in childhood should have been given (since they claim that a post-vaccination 'regression' from typical development took place). Instead, they chose to diagnose autism. Why? Because it wasn't autism that was being observed, if the claims made in the paper were true. Here's a clue: childhood disintgrative disorder is very rare compared to autism (autism prevalence being about ten times that of childhood disintegrative disorder).

As for what background I have to say all this: I have a copy of the ICD 10 Chapter 5, and access to a copy of the DSM IV should I need it; I trained as a specialist in autism and other issues affecting learning and development; I collaborate with a local training provider on autism issues; I have a BA-equivalence in applicable psychology (Finnish universities did not routinely award bachelor degrees when I matriculated into the University of Birmingham); I have a Master of Education degree that was taken inthe Division of Special Education, Educational Psychology and Inclusion (I focused on the psychology of teaching, learning and development), and I was awarded my degree 'with Distinction' because I knew my stuff and could explain it well; I completed a Certificate of Professional Specialisation in Education (Educational & Organisational Ethno-Psychology) at the University of Applied Sciences in Jyvaskyla** (this was done by research, with the development project being a proto-proposal for doctoral study; topic: 'Autism as a para-cultural phenomenon'); I am an occasional Visiting Lecturer at my alma mater, having tutored and supervised a student of theirs in Finland (and it is me that they ask to revise their distance learning materials in the autism options); I am also international associate editor in Finland for the journal Good Autism Practice. I'd say that this is a reasonable background from which to say anything meaningful on autism and learning & developmental difficulties. You may not think so, but that's just you. Many others do, and they are the important ones.

I suggest that you start looking at your belief system and loosen up your schemata: they are clearly holding your education back.

** the a-with-umlaut character does not show in this form, so I have substituted a for it.

Competing interests: None declared

David N Andrews, psychologist, writes:

"A bit egregious with your avoidance issues, are you not? The paper was published in 1998: the definition of autism current at the time - in the United States - was that in DSM IV. In the UK, where these children were assessed, the definition used was that found in ICD 10, Chapter 5."

The terminology in the title of the paper "pervasive development disorder" is from DSM-IV [1]. The paper states that the neurological and psychiatric assessment were done by consultant staff Peter Harvey and Mark Berelowitz under 'HMS-4 criteria' which as footnote "1" makes clear is a typographic error for DSM-IV. I question that a professional such as Andrews should enter into published discussion without checking the text of study and with an apparently revisionist historical agenda. I believe this illustrates how farcical the pillorying of Wakefield has become. And were not the actual diagnoses made by Harvey and Berelowitz, and not by Wakefield who is now being accused of fabricating them?

Another problem I would like to briefly highlight in Deer's account of the medical history of Child 1.

"Child 1's recorded story began when he was aged 9 months, with a 'new patient' note by general practitioner Andrea Barrow. One of the mother's concerns was that he could not hear properly--which might sound like a hallmark presentation of classical autism, the emergence of which is often insidious. Indeed, a Royal Free history, by neurologist and coauthor Peter Harvey, noted 'normal milestones' until '18 months or so.'" [2]

However, Wakefield, familiar with the point from Deer's earlier newspaper article writes in his book on the affair.

"A review of the additional GP records (not available to the Royal Free teem at the time of writing The Lancet paper) show with respect to his claim about Child 1's hearing, Deer failed to mention the crucial fact that in the entry documenting the mother's concern about Child 1's hearing, her additional concern was about a discharge from the child's left ear." [3]

In an article in the Sunday Times yesterday Deer states that he insisted that the BMJ jounal staff check all his facts [4], but did they?

BMJ is levelling charges of the utmost professional gravity and of an almost unprecedented kind, so they ought to make sure they have their facts straight. Or they should retract.

[1] Wakefield et al, 'Ileal-lymphoid-nodular hyperplasia, non- specific colitis and pervasive development disorder in children", Lancet 1998.

[2] Brian Deer, 'Secrets of the MMR scare, How the case against the MMR vaccine was fixed', BMJ 2011; 342:c5347 doi: 10.1136/bmj.c5347 (Published 5 January 2011)

[3] Andrew Wakefield, 'Callous Disregard Autism and Vaccines: The Truth Behind the Tragedy', Skyhorse Publishing, New York 2010, p.191.

[4] Brian Deer, 'A warning shot for the cheats in white coats', Sunday Times 9 January 2011.

Competing interests: Autistic son

Alex Snelgrove... something for you:

"I am certain that what most parents of a child with regressive-type autism want to know is what happened to their child's brain. I certainly do."

Who wouldn't want to know what was going on?

"Not only was my son's physical development from birth normal, he was also bright and alert."

Here's a criterion for you:

A. Apparently normal development for at least the first 2 years after birth as manifested by the presence of age-appropriate verbal and nonverbal communication, social relationships, play, and adaptive behavior.

"Before he was two, he knew who he was, and he knew who we were. He knew he was a member of our family and he could relate well until shortly after his second birthday when his personality and behaviour gradually changed."

Another one:

C. Abnormalities of functioning in at least two of the following areas:

(2) qualitative impairments in communication (e.g., delay or lack of spoken language, inability to initiate or sustain a conversation, stereotyped and repetitive use of language, lack of varied make-believe play)

"Words that he was familiar with using and understanding weren't there for him any more, and severe behavioural problems ensued. Deafness was suspected at first because he didn't respond to his name but was dismissed by a standard hearing test."

B. Clinically significant loss of previously acquired skills (before age 10 years) in at least two of the following areas:

(1) expressive or receptive language

"He spoke to himself in jibberish"

Again: B. Clinically significant loss of previously acquired skills (before age 10 years) in at least two of the following areas:

(1) expressive or receptive language

"and was echolalic,"

And again:

B. Clinically significant loss of previously acquired skills (before age 10 years) in at least two of the following areas:

(1) expressive or receptive language

C. Abnormalities of functioning in at least two of the following areas:

(2) qualitative impairments in communication (e.g., delay or lack of spoken language, inability to initiate or sustain a conversation, stereotyped and repetitive use of language, lack of varied make-believe play)

"and at age four he still couldn't recognise or tell you his name."

Yet again:

B. Clinically significant loss of previously acquired skills (before age 10 years) in at least two of the following areas:

(1) expressive or receptive language

"At two, he became solitary."

Another two criteria: C. Abnormalities of functioning in at least two of the following areas:

(1) qualitative impairment in social interaction (e.g., impairment in nonverbal behaviors, failure to develop peer relationships, lack of social or emotional reciprocity)

B. Clinically significant loss of previously acquired skills (before age 10 years) in at least two of the following areas:

(2) social skills or adaptive behavior

"His speech therapist suspected autism."

Understandable, but wrong.

"His pediatrician diagnosed him with Asperger's Syndrome, at that time considered to be the high-functioning form of autism."

That was such a bad diagnosis that it wasn't even good enough to be wrong!

"An autism specialist diagnosed Developmental Aphasia, Central Auditory Processing Disorder and hyperaccusis."

This I cannot understand the basis of...

"A world-renowned autism expert we consulted in the mid 1990s said my son didn't have autism or Aspergers Syndrome because there was a valid explanation for his behaviours. They stemmed, he said, from his severe language and auditory processing disorders."

They were correct in the first part. As for the second, I'm not so sure.

"Soon afterwards, the result of Dr Bernard Rimland's ARI checklist for autism arrived in the mail. My son had Classic Kanner's Syndrome."

Sorry, but - as you'll soon see - this is also incorrect; plus, ARI's forms... they are not good. Even with the information you have given I can tell you what people at your end should be looking at for the correct diagnosis.

I'll mark in the block quote the things you have mentioned so far...

(QUOTE)

A. Apparently normal development for at least the first 2 years after birth as manifested by the presence of age-appropriate verbal and nonverbal communication, social relationships, play, and adaptive behavior. THIS ONE

B. Clinically significant loss of previously acquired skills (before age 10 years) in at least two of the following areas:

(1) expressive or receptive language THIS ONE (present earlier and then lost)

(2) social skills or adaptive behavior THIS ONE (present earlier and then lost)

(3) bowel or bladder control

(4) play

(5) motor skills

C. Abnormalities of functioning in at least two of the following areas:

(1) qualitative impairment in social interaction (e.g., impairment in nonverbal behaviors, failure to develop peer relationships, *lack of social or emotional reciprocity*) THIS ONE

(became solitary; personality changed)

(2) qualitative impairments in communication (e.g., delay or lack of spoken language, *inability to initiate or sustain a conversation*, *stereotyped and repetitive use of language*, lack of varied make-believe play) THIS ONE

(spoke in jibberish; echolalic; could not recognise or tell his name)

(3) restricted, repetitive, and stereotyped patterns of behavior, interests, and activities, including motor stereotypies and mannerisms

D. The disturbance is not better accounted for by another specific Pervasive Developmental Disorder or by Schizophrenia.

(END QUOTE)

I can tell you - based on what you have told here - that criterion D is also fulfilled.

From what you say, you son does indeed have a named syndrome, but it is neither Asperger syndrome nor Kanner syndrome. Given the prima facie fulfilment of the criteria in the block quote, the diagnosticians in your son's case should be investigating the possibility of Heller syndrome (DSM IV-TR: 299.10; ICD 10 CH5: F84.3).

The ICD 10 introductory description of Heller syndrome is as follows:

(QUOTE)

F84.3 Other childhood disintegrative disorder

A type of pervasive developmental disorder that is defined by a period of entirely normal development before the onset of the disorder, followed by a definite loss of previously acquired skills in several areas of development over the course of a few months. Typically, this is accompanied by a general loss of interest in the environment, by stereotyped, repetitive motor mannerisms, and by autistic-like abnormalities in social interaction and communication. In some cases the disorder can be shown to be due to some associated encephalopathy but the diagnosis should be made on the behavioural features.

Dementia infantilis

Disintegrative psychosis

Heller's syndrome THIS NAME

Symbiotic psychosis

(END QUOTE)

The actual criteria are - for all practical purposes - the same as the DSM IV-TR set... any differences are minor (DSM has traditionally followed ICD lines). ICD 10 actually specifies that the behavioural outcomes in section C are 'autistic-like'.

This is not a diagnosis; nobody can make a diagnosis without seeing the person being diagnosed. Rather, this is an attempt to shed some light on your son's development and how it really ought to be interpreted diagnostically.

Your son would seem to have gone along a developmental path more suggestive of Heller syndrome than any other PDD-list syndrome. I hope this clears a few things up. Incidentally, Heller syndrome was the original PDD listed in the research that Wakefield had been doing (at least, based on the evidence presented by Brian Deer on his site pages regarding the Wakefield scandal).

I am likely to be writing an article on Heller syndrome shortly.

David N. Andrews M. Ed., C. P. S. E.

Psychologist (Teaching, Learning & Development)

Finland

Competing interests: None declared

John Stone: "In the light of this it would seem that the central theme of Brian Deer's article rests on an outdated (DSM IV 1994) definition of Autism."

A bit egregious with your avoidance issues, are you not? The paper was published in 1998: the definition of autism current at the time - in the United States - was that in DSM IV. In the UK, where these children were assessed, the definition used was that found in ICD 10, Chapter 5.

Competing interests: None declared

UCL takes any allegation of research misconduct very seriously, and we will certainly investigate those raised in the BMJ. At this point, however, we have not been given the opportunity to view all of the articles to be published in the BMJ relating to this issue. We are therefore currently able to give only a general institutional response to the issues so far raised.

At the time the research relating to February 1998's Lancet paper was conducted the Royal Free Medical School was not part of UCL. The Royal Free and University College Medical School was formed via a merger of the two schools in August 1998 and has been known as UCL Medical School since October 2008.

It is over a decade since this research was carried out and major relevant institutional changes in that time mean that circumstances are very different from when these events occurred. Significant changes include a reorganisation of ethics approval processes and a merger of previously separate research and development activities at UCL, University College Hospitals NHS Foundation Trust and the Royal Free Hampstead NHS Trust.

This latter step has provided a much greater degree of integration, improved exchange of information across the NHS-University boundary, and the establishment of common processes and standards. Substantial additional resources have been made available for research and development within UCL, meaning relevant regulatory processes and the overall monitoring and audit of research have all been improved.

In light of the GMC's findings in January 2010, UCL initiated a review of its present research governance structures and processes to test their robustness in the context of the case. This review, which is ongoing, aims to identify any lessons that can be learnt and ensure that everything possible is in place to prevent a similar situation in the future.

In reference to the BMJ's recent request for UCL to investigate Andrew Wakefield's research papers, we fully acknowledge the need to look closely at the research of someone alleged in your article to have carried out research misconduct and for this process to be subject to external scrutiny, in line with our procedures in this area. We are carefully considering how we might conduct this investigation in light of the complex legal, practical and logistical aspects involved.

We are determined to learn from the mistakes made in relation to this case. It will, unfortunately, never be possible to have a system which absolutely guarantees to prevent research misconduct - and it is vital that governance procedures avoid obstructing valuable research. Our objective is to continue refining a structure and processes which provide all reasonable safeguards whilst also facilitating the highest quality research for population benefit.

Professor Sir John Tooke, Vice-Provost (Health), UCL
Professor David Price, Vice-Provost (Research), UCL

Competing interests: None declared

The book, 'The Cry and the Covenant' by Morton Thompson was first published in 1949: I read it as a teenager in 1975. The novel, based on the life of Ignaz Semmelweis, a Hungarian obstetrician, profoundly affected me and certainly influenced my decision to become a doctor.

Puerperal fever was common in mid-19th-century hospitals in Europe and there was a high mortality - between 10 - 35% at that time. By 1847, Semmelweis had discovered that the incidence of puerperal fever could be drastically cut by hand-washing with a chlorinated lime solution. His research and the statistics he compiled showed that in the Vienna General Hospital, the doctor's wards had three times the mortality of the midwife supervised wards. The application of the Semmelweis practice of hand- washing reduced puerperal mortality to below 1 % and subsequently earned him the description of "saviour of mothers".

Sadly, Semmelweis's observations conflicted with the established scientific and medical opinion of the time; his perfectly reasonable hand- washing suggestions were ridiculed and rejected by his contemporise and by Professor Johann Klein, the medical director and his first boss in Vienna. Klein is alleged to have instructed,

"'Keep yourself to what is old, for that is good. If our ancestors have proven it to be good, why should we not do as they did? Mistrust new ideas. I have no need of learned men. I need faithful subjects. He who would serve me must do what I command. He who cannot do this or who comes full of new ideas may go his way. If he does not, I shall send him.' Do you understand, Dr. Semmelweis?"

It was Klein who subsequently stripped Semmelweis of his university position and repeatedly blocked his career progress in Vienna. However, Dr Semmelweis did have some support among his students, and JF von Arneth explained how he saw the situation of medicine vis-a-vis his innovation, and innovations in general.

"Do you know," said Arneth slowly, "it's true of your discovery as it has been of every discovery in the whole history of medicine. When we take our medical oath we undertake to lengthen life and ease suffering. We are all united in seeking new means. And every time a man has come forward with a demonstrable truth, a remedy for good, the profession seems to have done its best to crush the discoverer and hide the discovery. No quackery - no criminality - nothing seems to make us so furious as a discovery." [1]

Of course, the 'Semmelweis reflex' is a metaphor for a certain type of human behaviour characterised by a reflex-like rejection of new knowledge because it contradicts entrenched norms, beliefs and other establishment paradigms.

[1] The Cry and the Covenant by Morton Thompson, Published by Garden City Books/NY in 1949. Book Review by Bobby Matherne, 2010. http://www.doyletics.com/arj/tcatcrvw.htm

Competing interests: None declared

In December 2009, the World Health Organisation (WHO) announced a 78% decline in global measles deaths between 2000 and 2008, from 733,000 (uncertainty bounds 530,000 - 959,000) to 164,000 (115,000-222,000). The uncertainty bounds calculations were "based on Monte Carlo simulations that account for uncertainty in key input variables i.e., vaccination coverage and case-fatality ratios". A summary of measles case notifications received from 169 (88%) - 180 (94%) nations between 2000 and 2008, respectively, indicated that, globally, measles cases reduced from 852,937 in 2000 to 278,358 in 2008. These figures include "aggregated annual case counts as reported by member states".1,2

Given the short incubation period (10-14 days) of measles, these figures appear to suggest that the case-fatality ratio for measles varied, on average between 86% in 2000 and 59% in 2008. Yet, rigorous reviews studies have shown that case fatality ratios for measles are generally between 5-10%, with only one major outlier out of 102 studies - a case- fatality ratio of 40.16% from a 1981 study in rural Gambia. Prospective studies of case fatality ratios are inherently unethical, while retrospective studies may be compromised by recall bias, difficulty ensuring that rash and fever cases are truly attributable to measles, and challenges in obtaining a representative sample of measles case- patients.3,4 nevertheless, the validity of 2000-2008 global measles data remain questionable. WHO defines a measles-associated death as "one occurring within 30 days of rash onset, not obviously due to another cause such as trauma".5 This criterion is practical and feasible for vital registration in developing nations. It is more probable that numbers of new measles infections are being chronically under-reported, partly due to international pressure on health bureaucrats for "progress results", and potential conflicts of interest - the health ministry officials authorised to compile measles annual reports are the same staff employed to reduce measles incidence through vaccination and case management. Just as new epidemiological tools data enabled the downward revision of global maternal mortality numbers in 20106, systematic analyses of the measles caseload is likely to result in upward revision of global measles incidence. Such analyses are urgently required.

References

1) Dabbagh A, Gacic-Dobo M, Simons E et al. Global Measles Mortality, 2000-2008. MMWR, 2009; 58: 1321-1326.

2) World Health Organization. Global measles deaths drop by 78%, but resurgence likely. Geneva, WHO Media Release, 3 December 2009. URL: http://www.who.int/mediacentre/news/releases/2009/measles_mdg_20091203/en/index.html

3) Wolfson LJ, Grais RF, Luquero FJ, Maureen E Birmingham MB, Strebel PM. Estimates of measles case fatality ratios: a comprehensive review of community-based studies. Int J Epidemiol 2009; 38:192-205.

4) Cairns KL, Nandy R, Grais RF. Challenges in measuring measles case fatality ratios in settings without vital registration. Emerging Themes Epidemiol. 2010; 7: 4.

5) Byass P. Measles control in the 1990s: generic protocol for determining measles case fatality rates in a community, either during an epidemic or in a high endemic area (WHO/EPI/GEN/93.3). Geneva: WHO, 1993.

6) Wilmoth J, Zureick S, Mizoguchi N, Inoue M, Oesteergard M. Levels and trends of maternal mortality in the world. The development of new estimates by the United Nations. Geneva: United Nations, 2010.

Competing interests: None declared

I am certain that what most parents of a child with regressive-type autism want to know is what happened to their child's brain. I certainly do. Not only was my son's physical development from birth normal, he was also bright and alert. Before he was two, he knew who he was, and he knew who we were. He knew he was a member of our family and he could relate well until shortly after his second birthday when his personality and behaviour gradually changed. Words that he was familiar with using and understanding weren't there for him any more, and severe behavioural problems ensued. Deafness was suspected at first because he didn't respond to his name but was dismissed by a standard hearing test. He spoke to himself in jibberish and was echolalic, and at age four he still couldn't recognise or tell you his name. At two, he became solitary. His speech therapist suspected autism. His pediatrician diagnosed him with Asperger's Syndrome, at that time considered to be the high-functioning form of autism. An autism specialist diagnosed Developmental Aphasia, Central Auditory Processing Disorder and hyperaccusis. A world-renowned autism expert we consulted in the mid 1990s said my son didn't have autism or Aspergers Syndrome because there was a valid explanation for his behaviours. They stemmed, he said, from his severe language and auditory processing disorders. Soon afterwards, the result of Dr Bernard Rimland's ARI checklist for autism arrived in the mail. My son had Classic Kanner's Syndrome.

No wonder Brian Deer is confused about what autism is and what it is not. I dare say most people including medical professionals are similarly confused when mental health doctors now call autism a spectrum and refer to anyone with a condition on that spectrum as autistic. That, for instance, Albert Einstein, Bill Gates, Michaelangelo, Joy Adamson, Lewis Carroll, Jane Austen, Aldous Huxley, and Beethoven could possibly have had a remotely similar condition to Rain Man and the young man in The Black Balloon. And that two of the most prominent autism experts and authors, Simon Baron-Cohen and Tony Attwood, consider autism to be no more of a disability than left-handedness or simply a difference in personality which is a far cry from the early 1990s when autism was described as a devastating disorder which had a hopeless "there's nothing you can do" prognosis.

I think it is high time mental health professionals using behavioural checklists to diagnose autism took a back seat because this psychiatric diagnosis is totally meaningless and useless. It is merely a collective description for symptoms that may be severe, moderate, mild, or very mild. It doesn't give a clear picture of the person at all, or the reason for his or her difficulties. It is also an impediment to proper medical treatment because from the point of diagnosis onwards "the autism" is considered by health professionals to be the cause of all the problems that arise whether psychiatric or physical, and doctors won't look beyond to what is actually wrong with the child.

For some children, it could be an auditory problem, as Eileen Nicole Simon pointed out. Some hearing impaired children have similar behaviours to autistic children, called deafisms. Some blind children also have autistic behaviour, called "blindisms". Do our children with regressive autism suffer from perceptual problems? Yes they do. But these problems were not evident for the first 18 months or so in their development. Something happened to change the way their brains processed what they saw, heard, and touched. Anxiety replaced curiosity.

Andrew Wakefield was the first doctor to investigate the gastrointestinal symptoms of children with regression. He did not tell the parents that these problems were a symptom of their autism and turn them away, as most doctors would do. Wakefield's case study "associated (the children's regression) in time with possible environmental triggers". He did not say that autism is caused by the MMR vaccine.

The problem I believe is that medical specialists aren't getting their heads together over this. Gastroenterologists, neurologists, immunologists rely heavily on diagnoses given primarily by psychiatrists and psychologists when all they are doing is giving a subjective opinion based on a behavioural checklist. If the patient has verbal or non-verbal language impairments, social impairment, and engages in repetitive activities, it's autism which is, they say, a mysterious condition that doesn't have a cause or a cure.

Although I'm sure they're right that there isn't a singular cause or a singular cure for autism, there are definite causes for these symptoms, such as an encephalitis. Unfortunately, it is not the job of mental health professionals to investigate or identify a cause, or refer patients on to other specialists who might shed some light on the cause of the condition, so the child's parents are left floundering. And as we know from successful claims for vaccine injury compensation, those of Hannah Poling and Bailey Banks for instance, once the cause for the symptoms is known, the condition is no longer called autism. The symptoms are the result of vaccine injury that look collectively just like autism, but it's not autism.

Research should be focused on children with regression because epidemiological studies of children with an autism diagnosis are not going to identify the group of children who have lost skills. There is a huge difference between children born with a developmental disorder and those with regression. Watching your own mentally and physically normal child regress and lose skills and the ability to communicate and relate is a heartbreaking experience.

What Andrew Wakefield and his team did was what all doctors should do and that is to ignore the diagnosis and to physically examine the children to rule out medical causes for their regression and behaviour. Auditory processing disorders and sub-clinical epilepsy, for example. How many of our children with regression have epileptic conditions that are not being recognised by parents or doctors, and therefore remain untreated, resulting in a worse outcome? And when parents suspect seizures, is a twenty minute EEG sufficiently long enough to rule them out, or would an MEG be far more accurate? According to this study, "Although less than 15% of the (80) children had a history of clinical seizures, MEG revealed epileptiform activity in >60%." and " For approximately 20% of the children with an abnormal MEG, the simultaneous EEG was within normal limits."

http://imfar.confex.com/imfar/2009/webprogram/Paper5097.html

Our children with regression diagnosed with Pervasive Developmental Disorders are a severely neglected group. If Fiona Godlee, Jane Smith and Harvey Marcovitch, or Brian Deer, were to gradually lose their ability to speak and communicate over the next few weeks or months, developed aggression towards others and/or self, and began to engage in meaningless repetitive activities, I am quite sure they would want and their family members would expect medical doctors to carry out thorough physical examinations and a raft of tests to find out what is going on. They wouldn't calmly accept a psychiatrist's diagnosis whatever it might be because their symptoms matched one of his or her behavioural checklists, and he or she told them it was a mysterious condition that was untreatable. If I am right, why should they vilify Dr Wakefield for investigating bowel problems that were evident in his patients?

Would the authors agree that neither children nor adults have dramatic changes in their personality, stop communicating, have exaggerated responses to normal environmental stimuli and lose speech and other skills without a cause, and that it is negligent of the medical profession to not investigate a condition to search for that cause? Even if vaccines are implicated? Because what parents like myself want to know is: What happened to our children?

At least Andrew Wakefield was willing to take a look at one of the common symptoms that our children with regression have, while the rest of the mainstream medical profession appear to be content to sit on their hands, do nothing, and leave it to the psychologists.

Competing interests: My son regressed after vaccines. He has never received the MMR.

Dear Sir,

Since Rebecca Fisher is an interested Publishing executive, with apparently no stated vested interests, (although the words "as expected" and "apologists" result in a slight holding of breath..., but she raised a valid question which I would like answered. Which parts of Brian Deer's article are false?

Perhaps she (or someone like her) would be prepared to set up a website which would upload, with permission of the parents of all disputed 12 children (who would no doubt, be delighted to agree):

1) All the information the 12 specialists at Royal Free hospital had at their disposal while examining the children, as well as the files they constructed on the children;

2) Referral letters from GPs to Royal Free, describing the children's problems.

3) All the information from the GP and other files which Royal Free did not have at their disposal;

4) Web facilities to view any radiological scans which might be relevant.

Then set up an interactive forum (perhaps V-bulletin) with four forums:

a) One forum for Brian Deer can show with reference to the original data from the GPs and the hospital why he believes he is correct in all his statements.

b) Another forum for any or all of the 12 specialists involved in the original medical article, including Andrew Wakefield, to upload and comment on medical material, explaining why Mr Deer's article and many other statements are false, as well as any other related matters to these children that they, or Mr Deer wish to discuss.

c) A forum for the parents or family members of the 12 children, so that they can clarify any issues asked of them by either Brian Deer of Royal Free.

The participants for the three forums above, could have access to all three forums.

d) A fourth subforum within the forum ONLY allowing access for anyone else, to register at the site, and ask questions of either Brian Deer, or the 12 Royal Free experts on those two forums only..., so that the public and the media can be the judge of the answers based on factual original data.

Why do I suggest this?

Currently, we only hear Brian Deer's version of events, without anyone having reference to any original data.

"Climate-gate" came about as a result of a original data-concealment, (and potential manipulation of data). Calls for disclosure of all original climate data have now been heeded in the name of honest and open science (though, will that data be tweaked first?).

Given that all parties should have the same medical data, let's see them. If the issues Brian Deer writes about from that data, are as cut and dried as he says they are, then they are also cut and dried enough for anyone with a brain to also understand. Such data cannot possibly be copyright, or subject to concealment, since it rightfully belongs to both the parents and Royal Free, neither of whom presumably would have reason to deny public access to it, since if indeed, Dr Wakefield is wrong, both Brian Deer and Royal Free Hospital should be willing to prove it, and most certainly, the parents of the 12 children deserve correct answers from factual data, available for everyone to see.

Many in the public would be prepared to donate money through paypal, to a reputable publishing executive with supposedly no vested interests, or biased opinion..., who seemingly has expressed a genuine interest in knowing were Mr Deer might be erring ... and seemingly..., wants an explanation. Don't we all?

I hope that the suggestions above will inspire someone to provide an unbiased intelligent internet venue to discuss the issue in full, with all data, and all sides openly accountable, so that everyone can really unravel what happened, as well as to learn whatever lessons may come out of that.

Hilary Butler.

Competing interests: I love tracking bad science through the ages

Just to point out in relation to John R Smith's helpful contribution that the diagnostic criterion for autism in the Lancet paper was "pervasive development disorder", and was in the title. Therefore Brian Deer picking and choosing which PDD cases counted was spurious.

Competing interests: Autistic son

Dr Wakefield is charged with fabricating findings on the 'ideal world ' but unrealistic assumptions that medical records are always accurate and that medical practitioners and researchers always consistent in their record-keeping. It follows that for Brian Deer in medical research there could be few questions of interpreting facts and few grounds for disagreement over differing interpretations.

Deer's attack on Wakefield in this week's BMJ focuses on one set of data from the multitude provided on the 12 children in the 1998 Lancet 'early report': namely the record of when eight of the twelve children received their MMR in relation to the onset of behavioural signs that retrospectively were diagnosed as autistic spectrum disorders. Deer challenges the record that these children first displayed autistic signs following MMR and, ipso facto, questions the claim that they had a regressive form of autism. This is the main concern he raises from the rich array of data.

The timing of the symptoms in relation to the date the MMR was given refers to one of five hypotheses reviewed. Deer has less concern about the other hypotheses concerning inflamed or dysfunctional intestines (although in passing he points to disagreements over the diagnosis of bowel disease), the correlation between rising incidence of autism and MMR since its introduction in 1988 (which the paper rejects for lack of reliable data in the mid-1990s), the genetic predisposition to autistic-spectrum disorders, and vitamin B12 malabsorption.

Deer's focus on the timing of MMR, and his questioning of regressive autism and bowel disease, supports the claims of the manufacturers, government and medical profession that the MMR is safe.

Wakefield is charged with fabrication against an unrealistic standards of accuracy and consistency where no such standards exists. Notwithstanding the GMC's findings of fact, the reality is that medical records are not always consistent and that differences in interpretation do occur. For these charges to stand, they would need to be assessed against the uncertainties and contingencies that characterise real science, not against unreal and non-existent standards. Were the GMC and Deer to be the sole tribunal of truth in applying their standards of consistency to all medical research, then it would be questionable if research could progress in the way it has and if scientific debate were possible in the form so far conducted.

Wakefield provides an initial rebuttal to Deer's charges of falsifying evidence, first given in the Sunday Times, in his book 'Callous Disregard: autism and vaccines' (2010). Would the editors not agree that Wakefield has the right of replying to Deer's charges on grounds of fairness and even-handness?

Competing interests: father of autistic som

My son suffered a traumatic anoxic birth and had serious developmental delays. At 21 months of age we were told he had a "mild" form of cerebral palsy and would never be quite the person he might have been. He overcame all of his motor delays, but by age 4 remained deficient in language development. He spoke only in "echolalic" phrase fragments applied badly out of context. Just before turning 6 he began to speak normally, and his development took off by leaps and bounds. We did think he was cured until in his late teens he began a downward spiral.

The brain and how its impairment might lead to the characteristic (echolalic) language disorder became the focus of my personal research. The October 1969 issue of the Scientific American provided a plausible answer for me. In an article on newborn monkeys subjected to asphyxia during birth William F. Windle reported a finding of ischemic damage of brainstem nuclei, most prominent in the auditory pathway [1].

The brain needs to be the focus of research in autism. The language disorder of children with autism is distinctive, and therefore not the result of damage throughout the brain. The finding of auditory system injury appears much more related to language development.

Brainstem damage in other autonomic centers also resulted from asphyxia at birth, which should be considered a possible factor in GI disturbance in autism.

As for the increase in prevalence over the past 20 to 25 years, obstetric interventions rather than vaccination should be considered. Whereas traditional textbooks of obstetrics taught that fetal to postnatal respiration should be complete before severing the umbilical cord, the current written standard is to clamp the cord immediately after birth whether or not the infant has taken his first breath [2]. This can lead to asphyxia of duration long enough to cause impairment of brainstem centers for hearing as well as autonomic functions.

References

[1] Windle WF. Brain damage by asphyxia at birth. Sci Am. 1969 Oct;221(4):76-84.

[2] ACOG Committee on Obstetric Practice. ACOG Committee Opinion No. 348, November 2006: Umbilical cord blood gas and acid-base analysis. Obstet Gynecol. 2006 Nov;108(5):1319-22.

Competing interests: Mother of a son with autism

Thank you, Professor Miles: it was interesting to read your linked 'public radio' news article on the disturbing story of Somali migrants. The Minnesota autism riddle is altogether intriguing and I was stung into further reading by your recent take on the matter. [1]

There are now an estimated 50,000 or more Somalis living in Minnesota and Minnesota has the largest Somali population in the US. It was after 1992 that large numbers of Somali refugees began arriving in the US to escape the devastation of the civil war in Somalia. I understand that none of the Somali refugees had ever heard of autism back home, where there isn't even a name for the disorder. But in Minnesota, US-born children of Somali refugees were disturbingly proving prone to autism or what Somalis called Minnesota Disease: the reported rate was estimated at 1 in 28 refugee schoolchildren in 2008. Why? [2].

Nearly two years ago, at the end of March 2009, The Minnesota Health Department (MHD) published the results of a study, the Minnesota Somali autism study, which did grudgingly confirm that more Somali children were receiving autism services than other children. Why?

Understandably, the Somali community want answers; they want an explanation and then a solution to the conundrum. I wonder what contribution Professor Steven H Miles has made, or is willing to make, to finding a solution to the Minneapolis riddle.

[1] Controversial autism researcher tells local Somalis disease is solvable. Rupa Shenoy, Minnesota Public Radio, December 17, 2010. http://minnesota.publicradio.org/display/web/2010/12/17/somali-autism/

[2] Minneapolis and the Somali Autism Riddle. David Kirby, The Huffington Post, November 14 2008. http://www.huffingtonpost.com/david-kirby/minneapolis-and-the- somal_b_143967.html

Competing interests: None declared

Readers should be aware that the Diagnostic and Statistical Manual of Mental Disorders (DSM)Version 5 proposed revision has the following in regards to Autistic Disorder.

299.00 Autistic Disorder

New name for category, autism spectrum disorder, which includes autistic disorder (autism), Asperger's disorder, childhood disintegrative disorder, and pervasive developmental disorder not otherwise specified.

In the light of this it would seem that the central theme of Brian Deer's article rests on an outdated (DSM IV 1994) definition of Autism.

Some 16 years has passed and our knowledge and acknowledgment of Autism has grown exponentially.

Deer proposes using a very narrow definition referred to as "Regress autism" that only 1 child of the 12 should be acknowledged.

Under the new DSM V proposed definition that number would be increased

Child 1 Autism - Evidence Royal Free Admission

Child 2 Autism - Deer acknowledges

Child 3 Autism - Consultants letter

Child 4 Autism multiple concerns of parents and doctors

Child 5 Autism - Royal Free records 2001 "Regressive Autism"

Child 6 Autism - Diagnosed Asperger's Syndrome specialist.

Child 7 Autism - Diagnosed "Pathological Demand Avoidance Syndrome" is a PDD Pervasive Developmental Disorder - (Brother of 6)

Child 8 Unclear - Female - possible encephalitis / PDD abnormally small vocabulary. Documented febrile convulsion after MMR

Child 9 Unclear - Little documentation/history presented.

Child 10 Autism - Severe language and speech disorder with some autistic features.

Child 11 - Autism - Hospital discharge summary refers to Autism.

Child 12 - Unclear Specialist Development Unit reported "an impairment of language".

With this new tabulation of Deer's assessment and chart as provided in web extras we can now clearly see that all children had clear concerns over their development.

Deer states in footnotes "The regressive developmental disorder is tabulated as "autism" in nine cases. In study protocols, explanatory material for parents and clinicians,and post-publication commentary, Wakefield sometimes uses references to regressive autism interchangeably with "disintegrative disorder", although this is, in fact, professionally recognised to be a different disorder.

This is clearly not the case using the proposed DSM V definition.

regards

Competing interests: Father of son diagnosed with ASD / Special Education Teacher

This rapid response is another timely reminder that older medical publications are only too often a valuable source of a worthwhile and relevant knowledge. We are not wrong assuming that practically no medical students and practitioners read them.

However, I am asking myself just how many read even the latest medical information, also only too often relevant to their practice, such as a flier of NPS titled "New NPS national mass audience campaign: Be medicinewise". Dated 5 January 2011.

Let me quote verbatim the first paragraph:

"Later this month, NPS will start a long term national program to bring quality use of medicines to all Australians. This forms part of our longer term goals to improve safety and effectiveness of medicines use in the community. An estimated 1.5 million Australians experience adverse medicines events every year resulting in at least 400,000 visits to general practitioners and 140,000 hospital admissions. 1

Translated into $$, the medicines adverse events cost, very conservatively, some AUD 72.4 million per year. It is probably ten times more than that.

NPS stands for national patient safety.

A food for thought, perhaps? Or a mandatory reading?

Competing interests: None declared

It is rather interesting that Godlee et al choose to modify Deer's accusation that Wakefield et al "fixed the case against MMR" by referring to Deer as showing that "Wakefield's article linked MMR vaccine and autism...and was fraudulent", and rather disconcerting that three main editors of the British Medical Journal would utilise articles and data produced not by a scientist but by a journalist without qualifications or experience in any of the relative medical and psychiatric fields.

I read many adverse reports about Wakefield et al and various compelling rebuttals by Wakefield, and hold some admiration for Deer as an investigative journalist since his excellent expose of Wellcome in The Sunday Times many years ago that helped identify the dangerous antibiotic Septrin (co-trimoxazole) leading to a ban on its widespread use, both men seem dedicated to detail. After re-reading Wakefield et al 1998 and comparing it with the article by Deer claiming it "fixed" a case against MMR I think Deer misjudges his ability to analyse and interpret Wakefield et al, and I believe Wakefield et al provides a reasonable account of the circumstances of the research subjects.

Deer seems to be selective in his presentation of evidence. The assessments of the clinical pictures painted for each subject through scientific investigation via the Royal Free contrasts with Deer's apparent reliance on histology reports, excluding endoscopy, haematology and other tests and Deer seems happy to dismiss parental anecdote where it suits his arguments yet the Royal Free team has a responsibility to report and assess all available evidence from the subjects, their families and representatives. Consequently Deer presents errors and misconceptions that are easily observed in his two Tables of his "background document"; so using Deer's Table 1 (Deer's representation of Wakefield et al in their Clinical details and laboratory, endoscopic and histological findings Table 1 page 638, and Neuropsychiatric diagnosis Table 2 page 639) and Table 2 (Deer's own clinical and psychiatric evaluation of evidence available to Wakefield et al) I hope to demonstrate Deer's folly and identify where Wakefield et al might not be so clear: -

Child 1 aged 4 years. Deer disputes Wakefield et al on regression but does not deny it as he does any immediate post MMR events. At his references 47, 49 he says a parent stated the child merely became "pale" 7 -10 days after MMR but the story appears to be more complicated. The child, whose older brother is autistic, at 9 months of age "could not hear properly" but "had normal milestones till 18months old" and was vaccinated with MMR at 12months. Prof Walker-Smith found that the Child had possibly become delirious after the MMR shot with a possible fever. These possibles were reported by Wakefield et al as events within days of MMR in accord with parental anecdote; Deer chose to refute this and questions but does not deny the regression said to have occurred six months after MMR nor does he dispute the abnormal GI condition discovered.

Child 2 aged 9.5 years. Deer disputes that some regression and an abnormal GI condition, both of which he agrees occurred, did so immediately after MMR and therefore he disputes the mother's report of her son's head banging and screaming after MMR saying her report is "unsupported by any contemporaneous document". Wakefield et al faithfully record the mother's report to them.

Child 3 aged 7 years. Deer disputes but does not deny regression, or effects following MMR, but denies the GI condition, all of which Wakefield et al claim. The denial he bases on histology despite the report stating "mild inflammatory and reactive changes in small bowel samples of uncertain significance" were present in this 7 years old child some years after vaccination. Deer also fails to consider the extra evidence available to the research team, endoscopy noting LNH of terminal ileum, lowered MCA, much-elevated platelets, eosinophils and IgE. The child was reported to have walked at 13 months and used 2-3 words of speech then received MMR at 14 months and was said to regress and lose speech at 18 months.

Child 4 aged 10 years. Deer disagrees with Wakefield et al apart from a dispute rather than denial of regression. The mother believed he regressed, and the team faithfully reported this; also one of his doctors stated he believed the child's behaviour became increasingly abnormal. Deer cites the histology report that had no major abnormalities, though some minor. However, the team's endoscopy showed LNH of T ileum, and loss of vascular pattern in rectum. Additionally the lab investigations showed raised IgE, irregular IgG, much-elevated ALP and elevated AST.

Child 5 aged 8 years. Deer disputes regression and denies the GI condition. Deer's denial of the GI condition is based on histology report despite it stating there is "at best a minimal increase in chronic inflammatory cells" and "minor changes the significance of which are uncertain but do not amount to the diagnosis of IBD" around 6 years after vaccination. He ignores the endoscopy in this 8 years old child that records LNH of T ileum, proctitis with loss of vascular pattern.

Child 6 aged 5 years. Deer denies regression due to the child having a diagnosis of Aspergers S, and disputes post-MMR effect, but agrees on the GI condition which is described in histology as having a "mild patchy increase in inflammatory cells" and a "colonic series with a mild histologically non-specific proctocolitis". Deer's denial of post MMR effect relies on the child having been hospitalised three months before MMR after suffering a febrile convulsion and measles rash yet the mother then reported the child suffered changes in social interaction immediately after MMR including gaze avoidance and self injury. Their GP told the GMC he was worried about the mothers' reliability but one wonders why a GP would vaccinate with MMR a few weeks after hospitalisation with measles rash and febrile convulsion. Was this an accident, later faithfully reported by Wakefield et al, waiting to happen?

Child 7 aged 3 years. Deer denies regression and post MMR events; both deny the GI condition though endoscopy showed LNH of T ileum. The boy suffered epilepsy when enrolled for study. Deer denies post MMR event other than a seizure he deems probably normal for this epileptic child, yet the mother reports it as significant. The child Deer states "was reported before MMR with dragging one leg, having breath holding spells, a history of complex partial seizures and an incident of loss of consciousness for 20 minutes plus abnormal EEG, had been prescribed sodium valproate, a drug associated with possible ASD development. One must ask why was this child vaccinated with MMR, another accident waiting to happen, again faithfully recorded by the Royal Free Team? The lab findings for this child showed extraordinary levels for Hb, WBC, neutrophils and ESR.

Child 8 female aged 3.5 years. Deer and Wakefield agree on no regression but Deer denies the GI condition and post MMR effect based on histology yet this states there are "minimal inflammatory changes that may be the result of operative artefact" from prior aorta surgery. She had a documented convulsion two weeks after MMR with a diarrhoeal illness and records suggested a possible regressive episode. The endoscopy and lab findings, ignored by Deer, include LNH of T ileum and prominent ileal lymph nodes with abnormal IgA and IgG.

Child 9 aged 6 years. Deer states he and Wakefield agree on lack of regression and post MMR events but Wakefield et al record possible regression in this child at 18 months, just two months after MMR. Deer denies the GI condition based on no histological abnormality "other than prominent lymphoid follicles"; the endoscopy Deer ignores shows LNH of T ileum and patchy erythema at hepatic flexure. The child developed antibiotic resistant otitis media at 18 months, after MMR at 16 months, and behavioural symptoms of disinterest in sibling and lack of play.

Child 10 aged 4 years. Deer and Wakefield agree on no regression or post MMR effect but Deer denies the GI condition based on histology yet this states there was "lymphoid tissue showing reactive changes, large bowel mucosa with occasional isolated bifid glands" although a later report stated "confluent lymphoid aggregates within otherwise unremarkable small intestine" and " large bowel biopsies show subtle scattering of chronic inflammatory cells", "focal nuclear debris", epithelium slightly degenerate" albeit "not good evidence of gut inflammation in the biopsies". Endoscopy demonstrated LNH of T ileum, and lab tests confirmed abnormal IgG.

Child 11 aged 6 years. Deer denies GI condition and post MMR effects and disputes regression yet states that documentation is incomplete with limited histology available but refers to interviews with Child 11s father who to him "recalled a diagnosis of autism in California", and said his son never started to walk at an appropriate age, speech came slowly such that "even at age two there was no speech"; and he received MMR at 14 months after which the child developed a chest infection, for which Deer says the discharge summary states that "the parents noticed what they felt was a gradual deterioration in the son about a month before MMR". Endoscopy showed LNH of T ileum, lab tests showed abnormalities of Hb, IgA and IgM and the team record a report that this child suffered recurrent viral pneumonia for 8 weeks following MMR.

Child 12 aged 7 years. Deer states that he and Wakefield agree on no post MMR effect but Deer denies regression and the GI condition. The diagnosis he says was "an impairment in respect of language" not specifically regression, although this may be arguable, and histology was normal. Endoscopy showed LNH on barium follow through, colonoscopy normal and ileum not intubated, with lab tests showing abnormal IgA.

Of 36 specific categories for comparison in Deers' Tables for which he claims his are correct, there remain for Wakefield et al a total of 17 in agreement and therefore 19 at odds with Deer which Deers uses to claim impropriety by Wakefield et al. My conclusion would be that Deers data is inaccurate and of 36 categories Deer compares his opinion with that of the Royal Free Research Team I find only 5 items where Deer's opinion might outweigh Wakefield et al as far as evidence provided in Deers article and the paper by Wakefield et al. These are Child 9 GI diagnosis, Child 11 regression and post MMR effects, and Child 12 regression and GI diagnosis. For Child 9 there is a lack of lab data but histology "shows prominent lymphoid follicles" and in LNH this might be significant. For Child 11 the records are unclear and parental anecdote to Deer seems confused with no mention of the 8 weeks viral pneumonia following MMR. For Child 12 histology is limited but the mention of lymphoid follicles with germinal centres may be significant with LNH on barium follow through to Wakefield et al yet not Deer.

With 5 opinions in Deer's favour, though arguably so, one finds 14 in Wakefield et al's favour which effectively demonstrates that it is not the Royal Free Team, but Deer, who is a purveyor of potentially misrepresentative material.

I am reminded of the Teams findings

"Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with age-matched controls (p=0.003), low haemoglobin in four children, and a low serum IgA in four children. INTERPRETATION: We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers

Competing interests: None declared

Until and unless we compare the vaccinated to the never vaccinated, we will never know if vaccines, whether in general or specifically, result in better health outcomes for those who are administered them.

And forget the argument that people who don't vaccinate might be different and that might affect the results: If the never-vaccinated are healthier than the vaccinated, wouldn't we want to know it? We could then go about trying to understand why.

The failure to do such studies speaks volumes.

As far as using the excuse that there are limitations and difficulties with conducting such studies, fine. Don't do them. But stop pretending you know that the benefits of vaccines (far) outweigh the risks.

Finally, the hue and cry over the Wakefield paper is so out of proportion to the alleged wrongdoings, one has to wonder who's behind it and why it is happening.

If those who are claiming such egregious flaws really cared whether or not the Wakefield paper was fatally in err, they would do a properly designed and conducted retrospective study comparing those who have only gotten the MMR to those who have never been vaccinated at all. Only then might we get closer to the truth.

But that isn't going to happen, because there is no official interest in really knowing it.

So instead we get a smoke-screen designed to quell further debate and put the fear of God (or something) in anyone contemplating challenging the status quo.

Competing interests: I am President of the only website on the Internet that goes to great effort to publish all sides of the vaccination controversy.

As expected, the recent BMJ editorial and Mr Deer's article have brought a shower of Andrew Wakefield apologists out of the woodwork. Would Mr Stone et al care to explain precisely which part(s) of Mr Deer's damaging article they allege to be false?

Kind regards,

Rebecca Fisher

Competing interests: None declared

I am a physician board-certified by American Board of Psychiatry & Neurology who has specialized in autism for the last 13 years. I have trained hundreds of other physicians in the biomedical treatment of autism, and regularly mentor actively practicing physicians. I and other physicians with whom I work have had many children in our practices with history of Hep B vaccine at birth followed by regression into autism after the live triple MMR vaccine. Almost every patient with autism has some degree of gut disorder, and those with high rubeola antibody titers often have had the most intractable gut inflammation conditions in my practice.

I have never questioned Dr. Wakefield's association between MMR, autism and what is aptly named autistic enterocolitis and personally do not believe he has acted fraudulently. Along with hundreds of other physicians with waiting lists trying to help these suffering children I believe this uproar could be easily settled by a good study comparing autistic children who received Hep B at birth and then MMR with neurotypical children who have never been vaccinated (who are plentiful). Maybe a physician who has made millions off of vaccines and is a highly vocal vaccine proponent would propose/conduct such a study; it is obvious why vaccine makers would not like to do so.

Jaquelyn McCandless MD (author, "Children With Starving Brains, A Medical Treatment Guide for Autism Spectrum Disorder."

Competing interests: None

Can I just put it to the authors of this article Drs Godlee, Smith and Marcovitch (and to Dr Witkowski, Miles and Woo) that what is being claimed here borders on the impossible.

How could Wakefield have fabricated the data when there were 12 other signatories?

They should either explain this in clear detail or back down.

Competing interests: Autistic son

It can reasonably be assumed that some vaccines do cause damage to children or we would not have the Vaccine Damage Payments Act 1979. [1] The list of diseases to which this act applies includes measles and rubella as well as diphtheria, tetanus and whooping cough.

There does not appear to have been a consolidated paper that attempts to show how vaccines might cause brain damage by a review of the scientific literature except for the one that I have published on various web sites including scribd. [2] It has been published for open access. This paper looks at the causative factors mainly from the effects of the whooping cough vaccine (pertussis).

However, the U.S. Department of Health & Human Services, Centers for Disease Control and Prevention, National Immunization Program, promulgates that the risks from MMR vaccine can be permanent brain damage. [3]

Epidemiologists will probably say, and quite rightly, that the benefits of vaccination outweigh the occasional damage that is caused by some of them. The number of payments for vaccine damage in the UK is in excess of 1,000 and compared with the number of children who have benefitted, that number is miniscule bit not unimportant.

Over a thousand children will be living diminished lives as a result and their parents will be anguished that they were, in part, responsible for their child's disability.

For this lifetime of inequality and the loss of; normal education, a job and a life that contains the expectancies that most of us have envisaged and possibly achieved, the maximum award is, If you are severely disabled as a result of a vaccination, a one-off, tax-free payment of GBP120,000.

It is this shameful situation that ought to cause concern rather than a continuing denouncement of Wakefield. He may have got his understanding of the relationship between MMR and Autism wrong but that does not prove that there isn't one.

1 http://www.legislation.gov.uk/ukpga/1979/17/section/1

2 Challoner A. Brain Damage Caused by Vaccination. http://www.scribd.com/doc/19408267/Brain-Damage-Caused-by-Vaccination 2009.

3 http://www.cdc.gov/nip/publications/VIS/vis-mmr.pdf

Competing interests: I am the father of a vaccine damaged person.

Fiona Godlee asks: "Who perpetrated this fraud? ... We hope that declaring the paper a fraud will close that door for good."

For a very long time, the BMJ has occasionally focussed on how much of medicine does NOT stand on a solid base. BMJ also has said much about preventable medical error, which will kill far more children than parents deciding not to vaccinate their children. I have many articles from the BMJ archives about the 1940's treatment of diphtheria, measles and other diseases, which were it attempted today, would result in the administering doctors being had up for attempted murder.

The debasing manner of this "debate" is focussed sharply for me because of two books on my bookshelf. The first is Dr William H Holmes 1940 textbook called: "Bacillary and Rickettsial infections" which I bought last week for the princely sum of $7.58 (USA) and have just finished reading. This book was a discard from Harvard Medical School library. And I can see why it's a discard. The book is absolutely brilliant - interesting, erudite and far more informative than most modern textbooks I have.

This is the work of a man who worked up close and personal with all the diseases he wrote about, and who really understood his subject. But more than that, he was very widely read, and it shows. Why was this book discarded? Perhaps above all, because this man was honest, and delved deeply into why the standard treatments of most of the diseases covered, were more likely to kill the patient rather than cure. (Not something that the BMJ has ever discussed widely, to my knowledge...) He also expands a lot on historical standard practice of medicine in all those diseases, and what an eye opener. Treatment was barbaric at best, and torturous at worst. Which brought back to mind another book which I bought about three years ago, for $10.00 NZ.

This book was a discard from a public library, called "A History of Poliomyelitis" by Dr John R Paul, funded by Merck.

Dr Paul wrote truthfully about the absolute barbaric and cruel ridiculous treatment of poliomyelitis through the ages, which continued to the 1960's. Dr Paul also detailed how badly medical students were taught, right up to the 50's. And noted in passing, that many of those who went on to become "greats" simply bought their degrees. Hmmmm...

My point is this. The medical literature throughout the ages, has been full to the gunnels of accepted, unquestioned unsound science, which continues to this day. Most of that is never talked about. Why? If the public knew the history of medicine which medical journals never talk about, would that too destroy their faith in what their doctors have to say? And how do we know that accepted and unquestioned treatments of today, are really any better?

Unless medical students take the time to study books like the two mentioned above, they will not appreciate just how much of what they learn today, might still sit on a foundation of sand. Perhaps that's why so few medical libraries contain important books like these two.

William H Holmes had this to say in his introduction, which holds true for today's doctors:

"The text most popular with the student is the one which follows a conventional outline, which furnishes him the essential facts required for the passing of his examinations, and which serves as a ready reference in the solution of a specific medical problem. Such texts, no doubt, fill a need.

Nevertheless, the mere accumulation of facts, however valuable they may be in actual practice, cannot be regarded as an ideal form of education. The student who is interested in acquiring only immediately useful facts becomes a sort of tradesman or artisan actuated by the viewpoint that his sole obligation is to treat disease - the particular disease which a patient may happen to present. He is not likely to see his patient as a complex integrated organism whose many functions are intimately coordinated, interrelated, and interdependent. Neither does he see the patient in relation to the environment, and therefore cannot realise that illness is often the result of a long series of social and economic maladjustments, hereditary tendencies, insanitary conditions, vicious habits or education neglect.

Another defect in the form of education based on the accumulation of unasserted, poorly understood factual data is that it inevitable leads to atrophy of the critical faculties. How much more satisfying it would be to the young physician if, in his all-too-short period of training, he could find the time to study medicine as it has slowly evolved, and thus learn really to understand the relation of medicine to the growth of civilization..... he would gain a better insight into the obligations he assumed on becoming a member of the profession... he would sharpen his critical faculties while acquiring habits of thinking and study, and this would result in his becoming a man of wide interests and broad vision and, eventually, perhaps, in his becoming an educated physician."

What has this to do with the editorial above?

A lot. The removal of this book from a medical library is easily excused by the off-hand comment of "lack of space". But what this book would have afforded a student, was a real road map to critical thinking, unlike the textbooks of today, which are so often an exam-passing aid.

Which brings us back to my beginning paragraphs. How many of those so ready to leap into print, are utilising to the full,.... their critical thinking abilities?

Might those now passing judgement on Andrew Wakefield, be better served asking themselves the question, "Does the work I publish and do, conform to all the standards of scientific accuracy, rigour etc, which the BMJ and all others are now saying that Dr Wakefield's work lacked?"

How many pots are calling the kettle black? Or will that only be revealed in a medical text in 50 years time?

Why not review the many other undiscussed "elephants" still in the room, which today kill far more patients every day, than the lack of an MMR vaccine ever will?

Hilary Butler.

Competing interests: I very much enjoy studying bad science throughout the ages...

As humans, we are endowed with the ability to reason, not by believing, but by falsifying, but collectively we fail as a society to do just that. The fact that this is all because of a report based on 12 patients and that there have since been a series of well-designed control studies reporting the contrary makes it even more difficult to comprehend. We can't blame specific actors or actresses either as intelligence and rationality are not necessarily considered virtues in their particular profession. But as human beings, perhaps especially those who are in positions of influence, we owe each other to sharpen our intellect as serious inadvertent and very tangible damages can result and society can even be destroyed; in this case, one's child could die, say from meningitis, as a result of his neighbor's stupidity.

Competing interests: None declared

I agree with Mr. Sardi's comments. I have documented the epidemic of autism from 1992/1993 using the US Department of Education figures. Also I have found through a Freedom of Information Act (FOIA) request from the Social Security Administration that nationwide in the US, the numbers of adults/children with Autism Spectrum Disorder (ASD) collecting Social Security (SSI) benefits has skyrocketed from around 42,000+ in 2002 to 111,000+ in 2008.

In New Jersey, the state Division of Developmental Disabilities estimates nearly a quarter of 40,000 people it serves have autism as at least one of their diagnoses. Nationally, more than 250,000 students with autism were in schools in 2006-07, more than a 600 percent increase over a decade, according to the National Center for Education Statistics. And a 2007 National Survey of Child Health estimated that more than 680,000 children aged 2 to 17 have some form of autism -- a rate of 1 out of every 91 children.

In deed, I would think it would be more important to find out how the medical community could stop this epidemic by prevention and treat the children and adults that have regressive autism like our son. If it isn't done, all the denials about vaccines and autism will not stop this epidemic and it will be costly not only in economic terms but human terms.

Competing interests: Son who was born normal but regressed into autism after receiving the MMR vaccine based on home videotapes; and blood tests indicating elevated measles titer antibodies ten times above normal and testing positive for myelin basic protein antibodies

Mr. Wakefield continues his research in the United States. For example, he is studying a form of low pressure hyperbaric therapy for autism (http://clinicaltrials.gov/ct2/show/NCT00406159 ). This study was done in 2006 and finally apparently completed in 2009. He recently appeared in my state, Minnesota, to organize research on Somali immigrants (http://minnesota.publicradio.org/display/web/2010/12/17/somali-autism/ ).

His advocates cite his UK General Medical Council Status as "Registered without a licence to practise. Doctor erased. Not yet in force." They emphasize Mr. Wakefield's legitimacy by that last sentence. I appreciate the BMJ material but would hope the GMC would finalize the revokation of his fitness to practice.

Competing interests: None declared

It is most unfortunate to read the Andrew Wakefield episode, the physician being demonised for linking MMR vaccines with autism. In my opinion, he has erred on the side of caution, despite lack of appropriate scientific rigor, or accusations of fraud. A quick PubMed search shows that at least 500 articles relate vaccines with autism, with some suggesting that "U.S. male neonates vaccinated with the hepatitis B vaccine prior to 1999 (from vaccination record) had a threefold higher risk for parental report of autism diagnosis compared to boys not vaccinated as neonates during that same time period (Gallagher CM, Goodman MS.J Toxicol Environ Health A. 2010 Jan;73(24):1665-77). Other hypotheses suggest that the "combination measles-mumps-rubella vaccine causes autism by damaging the intestinal lining, which allows the entrance of encephalopathic proteins; (2) thimerosal, an ethylmercury-containing preservative in some vaccines, is toxic to the central nervous system; and (3) the simultaneous administration of multiple vaccines overwhelms or weakens the immune system" (Gerber JS, Offit PA..Clin Infect Dis. 2009 Feb 15;48(4):456-61.Vaccines and autism: a tale of shifting hypotheses)In Canada, researchers estimated the prevalence of pervasive developmental disorder with respect to MMR vaccination in 27,749 children from 55 schools in Quebec (Fombonne E, Zakarian R, Bennett A, Meng L, McLean- Heywood D. Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations. Pediatrics. 2006;118:e139-50).

Although 20 epidemiologic studies have shown that neither thimerosal nor MMR vaccine causes autism, it is not clear if the vaccine is entirely safe if used in the wrong way (any controlled studies?). And Dr.Wakefield's publications might have only highlighted the pitfalls associated with abuse of MMR vaccines in particular and vaccines in general. He has erred but only on the side of caution given the myriad biotech and pharmaceutical products out there, not one of which is entirely safe and efficacious. After all, it is a question of risk-benefit analysis, and if in some cases the risk is overhyped or exaggerated, it should not be a cause for concern. It is something to be appreciated, instead, despite all the missed childhood vaccinations!

Competing interests: None declared

The BMJ is to be congratulated on publishing Brian Deer's articles on Wakefield. Although the original study has long been discredited, it is essential to publish all the facts so as to regain the confidence of the public in biomedical research. Sadly, the new revelations are unlikely to shake the misplaced confidence in Wakefield of those families struggling with autism, nor diminish the industry of bogus therapies claiming to cure autism.

Competing interests: None declared

Will modern medicine please exert as much effort in determining the cause(s) of autism as it is in disparaging a research paper that should have never been published. Or was this paper published to become a "pin cushion" for vaccine advocates? And is there no criticism of vaccines at all? I have hard evidence that a flu vaccine in 1992 caused so many deaths it resulted in a decline in life expectancy in the U.S. The data is clear, but the link to the flu vaccine simply went unreported. When vaccines killed, modern medicine looked the other way.

Competing interests: None declared

Can anyone say why you would expect in the real world the medical history, as taken down by a leading consultant - in John Walker-Smith's case perhaps predominant figure in the field of study - to tally exactly with preceding GP compiled notes?

Incidentally, the GMC case hinged on the claim that the Lancet was a misconducted version of the Legal Aid Board protocol 172-96 and not an "early report" as stated. The panel, for which Harvey Marcovitch has executive responsibility, found this to be the case beyond reasonable doubt but I was unable to find any specific evidence cited in the findings on the fact that it was so. I wonder if anyone can explain this apparent lacuna?

The paper of course reported the history of adverse reaction to MMR vaccine in 8 cases but is it not rather egging the pudding - given the severity of the accusations - to say that it linked MMR and autism?

Competing interests: Autistic son