MMR

1.  Introduction

In February 1998, The Lancet, a UK medical journal, published Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. (A J Wakefield, S H Murch, A Anthony, J Linnell, D M Casson, M Malik, M Berelowitz, A P Dhillon, M A Thomson, P Harvey, A Valentine, S E Davies, J A Walker-Smith. The Lancet, Volume 351, Number 9103 28 February 1998) [1].

The paper contained a study conducted on 12 children who reported to have:

"chronic enterocolitis and regressive developmental disorder."

Wakefield et al presented their findings and conclusions as:

"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.

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."

In essence, Wakefield et al were claiming that these children began life as neurologically typical and that they regressed into autism and gastrointestinal disease at the same time as their MMR vaccination was administered.

2.  The Issues And Talking Points

2.1  Vaccine Uptake Slump

This paper was discussed heavily by its authors, especially Wakefield and prompted a world wide panic over the MMR vaccine with vaccination rates slumping lower and lower year on year until around 2004 in the UK.

2.2  The Validity of the Subjects

Wakefield claimed that the 12 children were gained for he study via routine referalls. It later transpired that just about every child in theb study was in fact a litigant involved in legal proceedings against vaccine manufacturers. Times journalist Brian Deer's subsequent investigation revealed that:

"...when he warned parents to avoid MMR, and published research claiming a link with autism, he did not disclose he was being funded through solicitors seeking evidence to use against vaccine manufacturers."

Deer further established that Wakefield had been paid up to £55,000 to find scientific evidence of a link and that he had not told his co-authors or the Lancet of his conflict of interest. One of the papers co-authors, Simon Murch said that finding out about the money was a very unpleasant surprise....All of us were surprised....We are pretty angry..

2.3  The Lancet Response

Richard Horton, Lancet editor was also reported to be angry and dismayed over the revelations. He told the BBC:

"There were fatal conflicts of interest in this paper. "In my view, if we had known the conflict of interest Dr Wakefield had in this work I think that would have strongly affected the peer reviewers about the credibility of this work and in my judgement it would have been rejected."

2.4  The Retraction

10 days after Brian Deer published his inital investigation into Wakefield, ten of the original thirteen co-authors withdrew their claim of finding a link between the vaccine and autism, stating:

"Consequent events have had major implications for public health. In view of this, we consider now is the appropriate time that we should together formally retract the interpretation placed on these findings in the paper."

2.5  Further investigations

Brian Deer conducted a follow up investigation for Channel 4 television's 'Dispatches' current affairs series. His findings revealed:

1. Nine months before publicly discrediting MMR, Wakefield and the Royal Free published a string of patent applications for rival vaccines. These products could only be viable if MMR's reputation was tarnished. Deer reports that all the patents (filed before the MMR paper was published) concerned the claim that measles in the MMR was to blame.
2. The Royal Free subsequently claimed that their products could 'cure' autism.
3. Wakefield's 'cure' claims were based on a technology called 'transfer factors'. This technology involves injecting mice with measles, extracting and processing white cells, injecting the result into pregnant goats, milking them after kid-birth and turning the product into capsules for human consumption.
4. Wakefield knew that science conducted in his own lab, using his specified methods had refuted his theory. One of Wakefield's colleagues at the Royal Free, Dr Nick Chadwick conducted tests on a larger sample of 22 children and concluded that:
   "None of the samples tested positive for measles, mumps or rubella RNA.....The results do not support previous data implicating persistent measles virus infection with the aetiology of IBD or autistic enteropathy."

3.  Outcomes and Further Details

3.1  Wakefield

Andrew Wakefield has effectively fled the UK, setting up Thoughful House, a private practice in Texas, USA. He will be facing GMC misconduct charges in the UK in 2006.

He has launched three seperate legal actions against Brian Deer and even against people who have reported upon Mr Deer's findings. In a letter sent by Wakefields legal team to the Cambridge Evening News, they said:

"You should be aware that proceedings in defamation have already been commenced against The Sunday Times in respect of the article published by Mr Brian Deer on 22nd February 2004. Your article has gone even further than the allegation in The Sunday Times which are currently being litigated and allege impropriety on the part of Mr Wakefield to receive money from lawyers to achieve a predetermined outcome."

As Wakefield had previously filed for a 'stay' of this action, Mr Justice Eadie presiding stated to Wakefield:

"In my view that paragraph was misleading. Mr Browne (Wakefield’s QC) argues that, even if the circumstances had been set out more fully and accurately, it would have made no difference to the outcome. The editor would still have acknowledged that he had got his facts wrong. That may be, but the important point at the moment is that the editor was given a misleading impression. Because of the stay, to which I have referred, the allegations in The Sunday Times were certainly not 'currently being litigated'. They were stayed pending the outcome of serious allegations of professional misconduct against the Claimant, to which no reference was made. It thus appears that the Claimant wishes to use the existence of the libel proceedings for public relations purposes, and to deter other critics, while at the same time isolating himself from the 'downside' of such litigation, in having to answer a substantial defence of justification."

Liberal Democrat MP Dr Evan Harris had criticised Wakefield on a radio programme. He also got a letter as did the Department of Health.

Justice Eady took a grave view of this also:

"I am quite satisfied, therefore, that the Claimant wished to extract whatever advantage he could from the existence of the proceedings while not wishing to progress them or to give the Defendants an opportunity of meeting the claims. It seems to me that these are inconsistent positions to adopt. This conduct is a powerful factor to be weighed in the exercise of the court’s discretion in circumstances which are clearly unique."

3.2  Other Studies

There have been numerous other studies. The CDC attempts to give an overview of them:

Pro MMR/Autism Link:

"The existing studies that suggest a causal relationship between MMR vaccine and autism have generated media attention. However, these studies have significant weaknesses and are far outweighed by the epidemiologic studies described above that have consistently failed to show a causal relationship between MMR vaccine and autism.

The MMR-autism theory is based on the idea that intestinal problems, like Crohn’s disease, are the result of viral infection and can contribute to the development of autism. The theory has its origins in research by Wakefield and colleagues (1989; 1990) which suggested that inflammatory bowel disease (IBD) is linked to persistent viral infection.

In 1993, Wakefield and colleagues reported isolating measles virus in the intestinal tissue of persons with IBD. However, the validity of this finding was later called into question when it could not be reproduced by other researchers (Afzal, 1998; Iizuka et al., 2000).

"Thompson and colleagues (1995) suggested in a retrospective cohort study that MMR vaccine might be a risk factor for Crohn's disease. However, the selection and recall biases and the differences in data collection in this study were so substantial as to cast doubt on the validity of the findings.

"Two studies out of Sweden linked measles infection in utero to the development of IBD (Ekbom et al., 1994; Ekbom et al., 1996). However, these studies involved a very small number of cases and when researchers identified the persons to be included in the 1996 study, they had prior knowledge that cases of Crohn’s disease had occurred in the offspring of two women who were infected with measles during pregnancy. This is called "selection bias" and limits the strength of the study.

"The MMR-autism theory came to the forefront when, in 1998, Wakefield and colleagues reviewed reports of children with bowel disease and regressive developmental disorders, mostly autism. The researchers suggested that MMR vaccination led to intestinal abnormalities, resulting in impaired intestinal function and developmental regression within 24 hours to a few weeks of vaccination. This hypothesis was based on 12 children. In 9 of the cases, the child's parents or pediatrician speculated that the MMR vaccine had contributed to the behavioral problems of the children in the study. There are a number of limitations in the Wakefield et al. (1998) study:

1) The study used too few cases to make any generalizations about the causes of autism; only 12 children were included in the study. Further, the cases were referred to the researchers and may not be a representative sample of cases of autism.

2) There were no healthy control children for comparison. As a result, it is difficult to determine whether the bowel changes seen in the 12 children included in the study were similar to changes in normal children, or to determine if the rate of vaccination in autistic children was higher than in the general population.

3) The study did not identify the time period during which the cases were identified.

4) In at least 4 of the 12 cases, behavioral problems appeared before the onset of symptoms of bowel disease; that is, the effect preceded the proposed cause. It is unlikely, therefore, that bowel disease or the MMR vaccine triggered the autism.

In 2004, 10 of the 13 authors of the study retracted the paper's interpretation, stating that the data were insufficient to establish a causal link between MMR vaccine and autism (Murch et al., 2004)

In another study that generated media attention and raised public concern in the UK (Uhlmann et al, 2002), researchers found measles virus fragments in the intestines of children with "new variant" IBD (children with both IBD and developmental disorder). Scientists looked for the presence of measles virus in the intestinal tissue of 91 children with new variant IBD and 70 "controls" (children without this type of IBD). The researchers found measles virus fragments in 75 out of the 91 children with "new variant" IBD, and in only 5 of the 70 controls. While this provides evidence for an association between the presence of measles virus and IBD in children with developmental disorder, it does not mean that the measles component of the MMR vaccine causes IBD or developmental disorder. As a commentary published with the article asserts, the data could just as easily be interpreted as indicating that the IBD or the developmental disorder cause the persistence of measles in the intestines (Morris & Aldulaimi, 2002). In addition, the researchers did not compare the virus found in the intestines of patients with the virus used in the MMR vaccine; nor did they provide information regarding whether or not the children in the study had been previously vaccinated with MMR or had previously contracted measles disease. The limitations of this study are further discussed in a letter written by the Director of CDC’s National Immunization Program to the UK’s Chief Medical Officer."

Anti MMR/Autism Link

"Epidemiologic studies have shown no relationship between MMR vaccination in children and development of autism:

In 1997, the National Childhood Encephalopathy Study (NCES) was examined to see if there was any link between measles vaccine and neurological events. The researchers found no indication that measles vaccine contributes to the development of long-term neurological damage, including educational and behavioral deficits (Miller et al., 1997).

A study by Gillberg and Heijbel (1998) examined the prevalence of autism in children born in Sweden from 1975-1984. There was no difference in the prevalence of autism among children born before the introduction of the MMR vaccine in Sweden and those born after the vaccine was introduced.

In 1999, the British Committee on Safety of Medicines convened a "Working Party on MMR Vaccine" to conduct a systematic review of reports of autism, gastrointestinal disease, and similar disorders after receipt of MMR or measles/rubella vaccine. It was concluded that the available information did not support the posited associations between MMR and autism and other disorders.

Taylor and colleagues (1999) studied 498 children with autism in the UK and found the age at which they were diagnosed was the same regardless of whether they received the MMR vaccine before or after 18 months of age or whether they were never vaccinated. Importantly, the first signs or diagnoses of autism were not more likely to occur within time periods following MMR vaccination than during other time periods. Also, there was no sudden increase in cases of autism after the introduction of MMR vaccine in the UK. Such a jump would have been expected if MMR vaccine was causing a substantial increase in autism.

Kaye and colleagues (2001) assessed the relationship between the risk of autism among children in the UK and MMR vaccine. Among a subgroup of boys aged 2-5 years, the risk of autism increased almost 4 fold from 1988 to 1993, while MMR vaccination coverage remained constant at approximately 95% over these same years.

Researchers in the U.S. found that among children born between 1980 and 1994 and enrolled in California kindergartens, there was a 373% relative increase in autism cases, though the relative increase in MMR vaccine coverage by the age of 24 months was only 14% (Dales et al., 2001). For more on this study, see California Data on Theory of Autism and MMR Immunization.

Researchers in the UK (Fombonne & Chakrabarti, 2001) conducted a study to test the idea that a new form, or "new variant," of Inflammatory Bowel Disease (IBD) exists. This new variant IBD has been described as a combination of developmental regression and gastrointestinal symptoms occurring shortly after MMR immunization. Information on 96 children (95 immunized with MMR) who were born between 1992 and 1995 and were diagnosed with pervasive developmental disorder were compared with data from 2 groups of autistic patients (one group of 98 born before MMR was ever used and one group of 68 who were likely to have received MMR vaccine). No evidence was found to support a new syndrome of MMR-induced IBD/autism. For instance, the researchers found that there were no differences between vaccinated and unvaccinated groups with regard to when their parents first became concerned about their child’s development. Similarly, the rate of developmental regression reported in the vaccinated and unvaccinated groups was not different; therefore, there was no suggestion that developmental regression had increased in frequency since MMR was introduced. Of the 96 children in the first group, no inflammatory bowel disorder was reported. Furthermore, there was no association found between developmental regression and gastrointestinal symptoms.

Another group of researchers in the UK (Taylor et al., 2002) also examined whether MMR vaccination is associated with bowel problems and developmental regression in children with autism, looking for evidence of a "new variant" form of IBD/autism. The study included 278 cases of children with autism and 195 with atypical autism (cases with many of the features of childhood autism but not quite meeting the required criteria for that diagnosis, or with atypical features such as onset of symptoms after the age of 3 years). The cases included in this study were born between 1979 and 1998. The proportion of children with developmental regression or bowel symptoms did not change significantly from 1979 to 1988, a period which included the introduction of MMR vaccination in the UK in 1988. No significant difference was found in rates of bowel problems or regression in children who received the MMR vaccine before their parents became concerned about their development, compared with those who received it only after such concern and those who had not received the MMR vaccine. The findings provide no support for an MMR associated "new variant" form of autism and further evidence against involvement of MMR vaccine in autism.

Madsen et al. (2002) conducted a study of all children born in Denmark from January 1991 through December 1998. There were a total of 537,303 children in the study; 440,655 of the children were vaccinated with MMR and 96,648 were not. The researchers did not find a higher risk of autism in the vaccinated than in the unvaccinated group of children. Furthermore, there was no association between the age at time of vaccination, the amount of time that had passed since vaccination, or the date of vaccination and the development of any autistic disorder. Though there were many more vaccinated than unvaccinated children in the study group, the sample was large enough to contain more statistical power than other MMR and autism studies. Therefore, this study provides strong evidence against the hypothesis that MMR vaccination causes autism.

DeStefano et al. (2004) conducted a study to see if there was a difference in the age at which children with autism and without autism received their first MMR vaccination. The study's findings showed that children with autism received their first MMR vaccination at similar ages as children without autism.

Source.

There has also been one non-epidemilogical study that examined the blood of autistic children in an attempt to replicate Wakefields findings - they failed to do so:

"This study failed to substantiate reports of the persistence of measles virus in autistic children with development regression." [2]

4.  Testimony

In 2007, during the course of the Cedillo hearing of the Autism Omnibus, Professor Stephen Bustin and Dr Nick Chadwick provided damning evidence of the poor science that underpinned the MMR causation hypothesis.

4.1  Professor Stephen Bustin

Bustin is possibly the foremost world expert on the techniques used in the lab that Wakefield claimed led to identifying Measles Virus (MV) in autistic kids gut and brain. The technique is called PCR. Not only does Bustin use PCR every day, he has 14 papers in the peer reviewed literature on PCR, over 8 book chapters and is personally the author of the A to Z of Quantitative PCR. which is considered 'the bible' of PCR. One of his papers has been cited over 1,000 times. Another has been cited over 500 times. He both organises and speaks at international PCR conferences.

Much of Bustin's testimony is highly technical but the essential facts of the matter are that every single published paper that supports the connection between MMR and autism went through one lab - The Unigentics lab in Ireland. Professor Bustin spent over 1500 hours in this lab examining their processes and procedures and found that:

• Due to the nature of the process Unigenetics employed, a contaminant had been introduced to samples.
• Consequently, the RNA Unigentics used was of very poor quality.
• A vital step (called the RT step) was missed whilst working on this RNA.
• Medical science dictates that if this step was missed and a target still identified that, by definition, it cannot be measles virus. This is because the if the RT step was missed the Unigentics team must have been dealing with DNA, not RNA and measles virus does not exist as DNA. They cannot possibly have detected measles virus in the gut of these children.

4.2  Dr Nick Chadwick

During the period of time that Wakefield was writing the Lancet paper, Nick Chadwick was a graduate students of Andrew Wakefield's and worked on the team that tested Wakefield's finding internally. Chadwick's 2007 testimony is reproduced below:

Q Okay. Did you personally test the gut biopsy samples for measles RNA?

A Yes.

Q What tests did you perform?

A A PCR test, a polymerase chain reaction.

Q What results did you receive from the gut biopsy materials for measles RNA?

A They were all negative.

Q They were always negative?

A Yes. There were a few cases of false positive results, which I used a method to see whether they were real positive results or false positive, and in every case they turned out to be false positive results. Essentially all the samples tested were negative.

.......

Q So you personally tested while you were in Dr. Wakefield's lab gut biopsy material, CSF and PBMCs?

A Yes, that's right.

Q And all the results were either negative, or if they were positive it always turned out that they were false positives?

A Yes, that's correct.

Q Did you inform Dr. Wakefield of the negative results?

A Yes. Yes.

This revealed that not only did Chadwick perform more accurate PCR testing than Wakefield, he also reported his negative findings to Wakefield who then totally ignored them.

5.  Blog resources (A - Z)

5.1  Autism Diva

1. Wakefield Cause of Autism Outbreak?
2. Andrew Wakefield is Just Trying to Help
3. Death rattle of the MMR Campaign?
4. Can Anyone Explain This?
5. MMR In Clear Over Autism
6. Autistic Intestinal Fortitude

5.2  Interverbal

1. Reflecting on Real Epidemic

5.3  Kevin Leitch

1. Open Letter to Andrew Wakefield
2. Lenny Schafer’s Cognitive Dissonance
3. Peter Fletcher, Melanie Phillips and the Daily Mail - A Cracked Facade
4. Andrew Wakefield: Beginning To Regret Libel Case?
5. MMR, David & Goliath
6. Trouble In Paradise? Thoughtful House with Staffing Problems
7. Isabella Thomas Gets Her Day In Court

5.4  Not Mercury

1. I Was Wrong!
2. Not Measles
3. MMR or Thimerosal?

5.5  Mike Stanton

1. Biomedical Interventions
2. MMR Again
3. Beyond Our Ken
4. An MMR Rant
5. MMR Survey reveals Deep Distrust of Government Health Advice

6.  Other Resources

1. Brian Deer: The Lancet Scandal
2. Brian Deer: The Wakefield Factor

7.  Also See

7.1  Papers

7.2  Other Theories

Thimerosal | RefrigeratorParents | Genetics | Sudden Increase In Autism | DataSources