Congressional Hearing – The Status of Research into Vaccine Safety and Autism

THE STATUS OF RESEARCH INTO VACCINE SAFETY AND AUTISM
HEARING
before the COMMITTEE ON GOVERNMENT REFORM HOUSE OF REPRESENTATIVES ONE HUNDRED SEVENTH CONGRESS SECOND SESSION
JUNE 19, 2002
 
Opening Statement
Chairman Dan Burton
In April the Committee conducted a hearing reviewing the epidemic of autism and the Department of Health and Human Service’s (HHS) response. Ten years ago, autism was thought to affect 1 in 10,000 individuals in the United States. When the Committee began its oversight investigation in 1999, autism was thought to affect 1 in 500 children. Today, the National Institutes of Health (NIH) estimates that autism affects 1 in 250 children.
In April we looked at the investment our Government has made into autism as compared to other epidemics. We showed in that hearing that the CDC and NIH have not provided adequate funding to address the issues in the manner that our Public Health Service agencies have used to address other epidemics.
After our hearing, I joined with my colleagues on the Coalition on Autism Research and Education to request from our appropriators that at least 120 million dollars be made available in FY 2003 for autism research across the NIH and at that an additional $8 million be added to the CDC’s budget for autism research.
Giving more money to research is not the only answer though. Oversight is needed to make sure that research that is funded will sufficiently answer the questions regarding the epidemic, how to treat autism, and how to prevent the next ten years from seeing the statistic of 1 in 250 from becoming 1 in 25 children.
High quality clinical and laboratory research is needed now, not five or ten years from now. Independent analysis of previous epidemiological and case control studies is needed as well.
We have learned that a majority of parents whose children have late-onset or acquired autism believe it is vaccine-related. They deserve answers. We have also learned that the parents have been our best investigators in looking for both causes of autism and for treatments.
It has been parents who have formed non-profit organizations to raise research dollars to conduct the research that the CDC, the FDA, and the NIH have neglected to do. We have heard from many of these parents in the past, Elizabeth Birt, Rick Rollens, Shelley Reynolds, and Jeanna Smith, to name just a few. Each of these parents had healthy babies who became autistic after vaccination.
I might have been like many of the officials within the public health community – denying a connection – had I not witnessed this tragedy in my own family. I might not have believed the reports from parents like Scott and Laura Bono, Jeff Sell, Jeff and Shelly Segal, and Ginger Brown, who came to me with pictures, videos and medical records. I might have been like so many pediatricians who discounted the correlation between vaccination and the onset of fever, crying, and behavioral changes. Because both of my grandchildren suffered adverse reactions to vaccines, I could not ignore the parent’s plea for help. I could not ignore their evidence.
My only grandson became autistic right before my eyes – shortly after receiving his federally recommended and state-mandated vaccines. Without a full explanation of what was in the shots being given, my talkative, playful, outgoing healthy grandson Christian was subjected to very high levels of mercury through his vaccines. He also received the MMR vaccine. Within a few days he was showing signs of autism.
As part of our investigation, the Committee has reviewed ongoing concerns about vaccine safety, vaccine adverse events tracking, the Vaccine Safety Datalink (VSD) Project, and the National Vaccine Injury Compensation Program. I have joined with Congressman Weldon, Congressman Waxman and 32 other members of Congress in introducing HR 3741, the National Vaccine Injury Compensation Program Improvement Act of 2002 to realign the compensation program with Congressional Intent.
In today’s hearing, we will receive a research update from several previous witnesses as well as new research findings that further support a connection between autism and vaccine adverse events. We will learn more about both the possible link between the use of the mercury-containing preservative thimerosal in vaccines and autism, as well as autistic entercolitis resulting from the Measles-Mumps-Rubella (MMR) vaccine.
Through a Congressional mandate to review thimerosal content in medicines, the FDA learned that childhood vaccines, when given according to the CDC’s recommendations exposed over 8,000 children a day in the United States to levels of mercury that exceeded Federal guidelines. Is there a connection between this toxic exposure to mercury and the autism epidemic? We will hear from Dr. James Bradstreet and Dr. Vera Stejskal on this issue.
We have twice received testimony from Dr. Andrew Wakefield regarding his clinical research into autistic entercolitis. We will learn today that not only has he continued to conduct clinical research, but that this research is confirming the presence of vaccine-related measles RNA in the biopsies from autistic children. Dr. Wakefield – like many scientists who blaze new trails – has been attacked by his own profession. He has been forced out of his position at the Royal Free Hospital in England. He and his colleagues have fought an uphill battle to continue the research that has been a lone ray of hope for parents whose children have autistic entercolitis. Dr. Arthur Krigsman is joining us as well today to discuss his clinical findings of inflammatory bowel disorder in autistic children. He will share with us his initial findings as well as discuss his research plans currently with his Institutional Review Board for approval.
Do the epidemiological and case control studies, which the CDC has attempted to use to refute Dr. Wakefield’s laboratory results, answer the autism-vaccine questions honestly? Epidemiologist Dr. Walter Spitzer is back today to answer this question. What else is needed to prove or disprove a connection?
Unfortunately, rather than considering the preliminary clinical findings of Dr. Wakefield as a newly documented adverse reaction to a vaccine, the CDC attempted to refute these clinical findings through an epidemiological review. While epidemiological research is very important, it cannot be used to disprove laboratory and clinical findings. Valuable time was lost in replicating this research and determining whether the hypothesis was accurate.
Officials at HHS have aggressively denied any possible connection between vaccines and autism. They have waged an information campaign endorsing one conclusion on an issue where the science is still out. This has significantly undermined public confidence in the career public service professionals who are charged with balancing the dual roles of assuring the safety of vaccines and increasing immunization rates. Increasingly, parents come to us with concerns that integrity and an honest public health response to a crisis have been left by the wayside in lieu of protecting the public health agenda to fully immunize children. Parents are increasingly concerned that the Department may be inherently conflicted in its multiple roles of promoting immunization, regulating manufacturers, looking for adverse events, managing the vaccine injury compensation program, and developing new vaccines. Families share my concern that vaccine manufacturers have too much influence as well. How will HHS restore the public’s trust?
Access to the Vaccine Safety Datalink (VSD)
One of the primary topics to be discussed at this hearing is access to the Vaccine Safety Datalink. (VSD). To help fill scientific gaps, the CDC formed partnerships with eight large health maintenance organizations through an agreement with the American Association of Health Plans to continually evaluate vaccine safety. This project is known as the Vaccine Safety Datalink (VSD) and includes medical records on millions of children and adults. Up until this year, access to data from the VSD has been limited to researchers affiliated with the CDC and a few of their handpicked friends. This ‘good old boy’s network” practice has predictably led to questions about the objectivity of the research and the fairness of the results.
The VSD data should be made available to all legitimate scientific researchers so that independent studies can be conducted and results verified. This database contains a wealth of data involving millions of patients over a ten-year period. If properly utilized, it can help researchers study vitally important questions about the safety of vaccines, the effects of mercury-based preservatives in childhood vaccines, and many other questions.
The Committee first raised this issue with the CDC two years ago. For two years the CDC delayed. Six months ago, we were informed that the CDC was developing a plan to expand access to the database. Finally, in February of this year, after a great deal of prompting from the Committee, Dr. Robert Chen, Chief of Vaccine Safety and Development at the National Immunization Program, informed Committee staff that the CDC had finalized its plan and that it was poised to put it into effect. Under this plan, any legitimate scientist could submit a proposal to the CDC to conduct research using VSD data and access to the data would be provided along with some basic safeguards.
In preparation for today’s hearing, Committee staff asked the CDC why the plan described to us in February had not yet been put into effect. The staff was informed that the plan had been put into effect. However, there had been no public announcement. How are researchers supposed to know about the availability of the data if there is no announcement? It took two years of prodding by this Committee to get the CDC to open up access to the database. For four months it appears that the CDC didn’t inform anybody but this Committee of the data’s availability.
That doesn’t make it appear that the CDC is making a good faith effort to open up this database. It looks to me like the CDC is trying to do the bare minimum that they have to do to get us off their backs. That’s not acceptable. That’s why I insisted that Dr. Chen be here today. I just want to ask him why they didn’t tell anyone about the database being available. I’d like to know how he expects researchers to use this data if nobody tells them it’s available.
Dr. Roger Bernier is here from the CDC to testify about these issues. He is accompanied by both Dr. Chen, the creator of the VSD Project and Dr. Frank DeStefano, the CDC official who is also a co-author of the MMR – IBD study. They are here to address our questions on the VSD project and the vaccine-
autism research. The CDC employees are accompanied by Dr. Stephen Foote of the National Institutes of Health and Dr. William Egan of the Food and Drug Administration.
As representatives of the people, we have a responsibility to ensure that our public health officials are adequately and honestly addressing this epidemic and its possible links to vaccine injury.
I look forward to hearing from our witnesses today. Our hearing record will remain open until July 3.
I now recognize the ranking minority member, Mr. Waxman for his opening statement.

Testimonies:
Jeff Bradstreet (PDF) Bradstreet Autism Congressional Testimony 2002

Walter O. Spitzer, M.D., M.P.H., F.R.C.P.C.
Emeritus Professor of Epidemiology, McGill University, Montreal
June 16, 2002
This scope of this opinion is limited to the Davis paper, to the extent that it is relevant to the objectives of the 06/19/02 congressional hearing at Washington D.C. (as summarized in Chairman Burton’s letter of invitation).
*The Davis paper cannot evaluate the relationship between Measles-Mumps-Rubella vaccine and/or Measles-Containing Vaccine (MCV) and an increased risk of Inflammatory Bowel Disease (IBD). The paper is flawed.
*The fatal flaw that negates the ability of the study to reach conclusions about the explored association is that it is grossly underpowered.
*The power for the key results (Table 2) is 12%. It was not reported in the paper. We (methodologists at the Royal Victoria Hospital clinical epidemiology unit and I) calculated power from the data in the paper. In non-jargon English, a power of 12% means that one has a chance of 88% of declaring no increase in risk if indeed there was a two-fold increase in the risk. In Table 3 of the Davis paper all power calculations for each cell demarcated by vaccination ages are similarly very low. Providing confidence intervals (CIs) is correct. But that is insufficient for the intelligent layman, the clinician, the patient and the policy-maker to detect how much power is lacking and to understand that such low power does not allow conclusions or decisions.
*It would appear that the Davis group reached their decision about necessary sample size based on advance assumptions of exposure of 70% (from their projection overheads) compared to 30% unexposed. In fact, the published paper reports exposure of 94% among the controls, compared to only 6% unexposed. It is this small 6% unexposed group that reduces the power. This should have alerted the investigators, early during the field work, that the proposed sample size would be inadequate, resulting in the serious underpowering.
*Given controls with exposure of 95 %, the sample sizes that would have been needed to detect a two-fold risk increase:
– For a power of 80% (conventional): cases 730, controls 2215;
– For a power of 90%: cases 930, controls 2820.
*As an epidemiologist focused on direct or indirect potential associations of vaccines, particularly MMR, with autism, and, by extension, IBD in autistic persons, I find the choice of outcomes strange. Restricting the outcomes studied to Crohn’s Disease and ulcerative colitis reduces the relevance of Davis’ work to current hypotheses about vaccine-IBD associations emerging from laboratory and clinical research.
*A hallmark of valid science is that it is verifiable and replicable. When a research project is done with governmental funds for equipment, material, space, etc. by investigators also supported with public funds, ethics and social responsibility dictate that resources be made available to replicate the project. In epidemiology, the size of typical undertakings is large. Usually, databases created are also large. The time for total replication would often be prohibitively long. Thus, such databases should be available to competent legitimate investigators with valid concerns also on grounds of ethics and social responsibility. “Fishing expeditions” by verifiers should be prevented with a priori research plans. If necessary, the plans should be reviewed by entities other than the database owners or funders. Controversial or inconclusive findings by honest investigators can be expected to benefit from verification and/or replication. Issues dealing with confidentiality of patients, doctors and other providers have been worked out for many years. Reasonable time should elapse from original creation of data and release of initial conclusions to verification. Neutral monitoring committees are generally important in such situations.
*All of the foregoing in the previous paragraph also applies to privately funded research with few exceptions such as patents and legitimate commercial considerations.
*I believe that the Vaccine Safety Datalink Project data should be made available to academic, governmental and competent private research groups for all the reasons given above. In this particular case, the VSDP, a public, publicly funded resource should be open with reasonable safeguards unless matters such as national security or an epidemic justified closing access. Temples of secrecy have no place in science. Secrecy always suggests the question, “What do they have to hide?”
*I reiterate that the case control study from the Vaccine Safety Datalink project cannot determine whether measles-containing vaccines do or do not increase the risk for inflammatory bowel disease.
I do not have any conflicts of interest. I have no nuclear or extended family members with any relevant disease, notably an autistic syndrome.. I have not had any grants for research or for any other purpose from US or other national sources since December 2000. As required by age, I retired this year I advise families of autistic persons in the UK pro bono. I do not know Dr R.L Davis personally nor any co-author of the paper commented upon. I do not further any view on association or causation with respect to MMR as a potential determinant of autistic syndromes. I am a worried agnostic, I do not know. I strongly believe we need to rule in or rule out a relationship. As an epidemiologist and public health doctor, my bias, if any, is that I would like to see MMR exonerated on safety, given its efficacy. Long and short versions of my CV have been submitted separately.

Arthur Krigsman MD

Mr. Chairman and members of the committee:
This testimony represents the scientific findings of data accumulated over the past year and a half from autistic children during the course of standard evaluations of their gastrointestinal symptoms. This testimony should in no way be taken as anti-vaccine. Children in my pediatric practice continue to receive all vaccinations in accordance with the guidelines set forth by the American Academy of Pediatrics. The observations expressed herein are my own, and do not represent the opinions of any institution, organization, clinic, or medical practice with which I may be associated.
My involvement with autistic children began approximately one and a half years ago. At that time, I was approached by a colleague who was caring for a large number of autistic patients. He observed that a large proportion of these patients suffered from chronic, unexplained gastrointestinal symptoms and that these symptoms were a source of great anxiety to the parents. I agreed to evaluate them, and my findings are detailed below. The evaluations undertaken were standard “textbook” evaluations of children with chronic diarrhea, constipation, and abdominal pain, uninfluenced by the fact that these children were autistic.
Patient Population
Our experience consists of a total of 43 consecutive children aged 2-10 years of age. Most were referred by private practitioners but many were self referred after much frustration with their children’s ongoing discomfort. 42 patients had received a diagnosis of either autistic disorder or autistic spectrum disorder by a pediatric neurologist or developmental pediatrician. Many children had received independent confirmation from a second or even a third pediatric specialist. In no instance was the diagnosis disputed by a second specialist. The remaining patient carried a diagnosis of Aspergers syndrome.
The majority of patients had a clear history of developmental regression. Specifically, these children developed in an entirely normal fashion for the first 12-18 months. They typically had a vocabulary of 15-25 words, maintained normal eye contact, were playful and interactive, and were not overly irritable. At some point during this age interval of 12-18 months, they had either a precipitous or gradual decline in all the above mentioned developmental markers, and this was accompanied by the appearance of typical autistic behaviors, “stimming”, and bouts of unexplained irritability. In some patients, verbal stagnation, but not regression occurred. However, in these patients, clear regression was seen in the interactive and social skills of the children.
The majority of patients are from the northeastern United States. The ratio of males to females was 7:1.
Symptomatology
The most common gastrointestinal symptom noted by the parents was diarrhea. In some children, the diarrhea took the form of a soupy liquid that occurred 4 to 7 times per day and would frequently leak from the child’s diaper. However, the majority of parents reported a stool frequency of 1-3 per day with a consistency of mashed potatoes. The stool is particularly malodorous, and usually contains pieces of undigested foods. Irritability is often noted just prior to the bowel movement.
Constipation is another frequent complaint, consisting of bowel movements every 3-6 days and typically accompanied by great irritability upon passage of the stool. The consistency of the passed stool was not overly hard, suggesting that these children are actually withholding stool and not truly constipated in the strict sense of the term. This constipation is often accompanied by abdominal distension and flatulence. Most patients experienced periods of diarrhea alternating with periods of constipation.
Abdominal pain is another frequent complaint. Most of these children are poorly communicative, and parents often rely on body language cues in determining that their child is experiencing abdominal pain. Children often drop unexpectedly to the floor howling and screaming. This often lasts for up to half an hour. Many children clutch their abdomen and bend over. Some assume a fetal position on the bed or floor, and others take the parents hand and rub their abdomen.
Finally, we have noticed that most regressive autistic children show poor growth, with the majority falling in the lower 10th %tile weight for age. Interestingly, there does not seem to be a concomitant percentile deficit in height for age.
Evaluation
All children underwent initial evaluation of their gastrointestinal symptoms. This included a thorough history and physical exam, complete blood count with platelets, erythrocyte sedimentation rate, serum chemistries, celiac antibody panel with serum IgA, inflammatory bowel disease serology, and stool examination for ova and parasites, culture, and occult blood. The patients diet was thoroughly reviewed to assure that it did not contain excessive nonabsorbed carbohydrates or fruit juices. Therapeutic alterations in the diet were undertaken, including the removal of all gluten and casein containing foods. Medications and supplements were reviewed to assure that they did not contribute to the symptoms.
The evaluation above invariably did not lead to a diagnosis and patients then underwent colonoscopy. Upper endoscopy was performed only if pain was a predominant complaint or if celiac disease was strongly suspected.
Findings
The above images depict the terminal ileum in two patients. They are representative of the gross endoscopic findings of 90% of these patients in whom the lymphoid nodules of the terminal ileum were found to be markedly enlarged. This is in agreement with the previously published findings of Dr. Wakefield in which a similar proportion of patients were found to have abnormal lymphonodular hyperplasia of the terminal ileum.
The second significant finding in our series was on histologic evaluation of the biopsy specimens. The results are summarized below.
% patients with colitis
28/43
65%
% patients with active colitis
22/43
51%
% patients with chronic colitis
17/43
40%
% patients with eosinophilic colitis
3/43
7%
% LNH (macro) of terminal ileum
36/40
90%
% neither active, chronic, nor eosinophilic
15/43
35%
Colitis was determined as per the report of the institutional pathologist. The interpretation of whether the degree of inflammation represented true pathologic inflammation versus a normal variant was subject to the personal experience of the individual pathologist and was not subjected to a uniform rating system.
The patterns of inflammation were patchy and unpredictable in any given patient, but overall were noted in all parts of the colon and terminal ileum. Although the table above lists chronic and active colitis separately, most patients with colitis had both chronic and active inflammation. Most patients had at least 3-4 distinct areas of histologic inflammation, with an equal number of biopsies that were histologically normal. The intensity of the inflammatory lesions varied as well, with many being subtle and somewhat focal, and others being more marked and diffuse. The latter included areas of cryptitis, crypt abscess, ulcerations, and dense inflammatory infiltration. One patient was found to have an inflammatory polyp. Most significantly, these findings were consistent and seen repeatedly amongst the majority of patients.
In regards to the last group of patients in the table above, it should be noted that although the histology did not reveal pathologic colonic inflammation, the majority of these patients were found to have a heavy and diffuse lymphoid hyperplasia of the colon (macroscopic and microscopic), signifying an activation of the colon’s internal immune system.
Conclusion
In a series of 43 autistic children, mostly regressive, with chronic gastrointestinal symptoms, the majority were found to have pathologic inflammation of the colon and terminal ileum. 90% had pathologic lymphonodular hyperplasia of the terminal ileum. Moreover, the findings were similar and consistent from patient to patient within the affected group.
Questions
1) Does autistic colitis occur equally in regressive vs. non-regressive autism?
2) Do differences in growth exist between the colitis and non-colitis group?
3) Do differences in growth exist between the regressive vs. non-regressive group?
4) In a retrospective analysis of growth, will onset of growth failure coincide with the onset of regressive behaviors?

Dr Andrew J Wakefield

June 19, 2002

Mr Chairman and members of the Committee,
Before bringing you up to date with the research linking MMR vaccine to regressive autism I will put the record straight with respect to Dr Gershon’s testimony last year on the molecular detection of measles virus in the laboratory of Professor O’Leary. Dr Gershon’s testimony was false in relation to a number of assertions, whether or not his testimony constituted perjury or simply sloppy science. It is not my wish to take up valuable time in this hearing with the details of Dr Gershon’s unacceptable errors. All correspondence and raw data have been provided to the ranking majority and minority members. Merely by way of illustration, he stated that tissues from experimental animals not infected with measles virus were positive in Professor O’Leary’s lab. In fact they were all entirely and consistently negative on repeat testing. Dr Gershon’s behaviour was a disgrace. I would level the same charge at anyone who relies or has relied in any way upon this testimony. I am not surprised that Dr Gershon turned down the offer to appear before this committee. Had he done so, I am sure he would have enlightened the Committee, somewhat belatedly, as to any proprietary rights his wife might have in the Merck chickenpox vaccine patent.
The current sate of the science:
The association between MMR vaccine, autism and intestinal inflammation was first suggested by my group from the Royal Free Medical School in 1998 in a paper published in the Lancet. The same research team, in collaboration with Professor John O’Leary and Dr Simon Murch from the Royal Free Hospital, has since shown in a comprehensive series of eight peer-reviewed scientific studies that the major findings of our original study were correct. These papers are listed as an appendix.
The sum of the research by my group and our collaborators, taken together with additional work by independent physicians and scientists in the United States has now confirmed the following facts.
Children with regressive autism and intestinal symptoms have a novel and characteristic inflammatory disease of their intestine (1-4).
This disease is not found in developmentally normal control children (2-4).
This disease is entirely consistent with a viral cause (5-8).
This disease may be the source of toxic damage to the brain (9).
Measles virus has been identified in the diseased intestine in the majority of children with regressive autism studied, precisely where it would be expected if were the cause of the intestinal disease (5,8).
These children, who suffer the same pattern of regressive autism and intestinal inflammation, come from many countries including the US and Ireland where they have been investigated and biopsied independently.
Measles virus has been found in only a small minority of developmentally normal children (5).
The measles virus in the diseased intestine of autistic children is from the vaccine (11).
Children with regressive autism appear to have an abnormal immune response to measles virus (1a,2a)
These findings are entirely consistent with parental reports that their normally developing child regressed into autism following exposure to MMR vaccine (1,11).
Confirmation of intestinal findings
Other researchers in the US have confirmed the presence of intestinal inflammation in children with regressive autism (3a & see testimony of Dr A. Krigsman MD) and, independently, the link with measles virus in children who were given the MMR vaccine (12,13).
Measles virus sequencing
Most significantly, a study due to be presented at the Pathological Society of Great Britain and Ireland, in Dublin at the beginning of July has confirmed that the measles vaccine virus is present in the diseased intestinal tissues of children with regressive autism.
The Dublin researchers headed by Dr John O’Leary, Professor of Pathology at Trinity College Dublin, examined viral genetic material from intestinal biopsies taken from 12 children with gastro-intestinal disease and an autistic spectrum disorder. The viral genetic material had already been identified as measles in a study published in January in Molecular Pathology. Using state of the art molecular science the samples from these twelve children have now been characterised as from vaccine strain measles virus. This investigation continues. These data constitute a key piece of evidence in the examination of the relationship between MMR vaccine and regressive autism.
Re-challenge and biological gradient effects for MMR/MR vaccines
A further key piece of evidence comes from examination of “re-challenge” and “biological gradient” effects for possible vaccine-related adverse events.
Re-challenge refers to a situation where re-exposure of an individual to an agent (e.g. vaccine) elicits a similar adverse reaction to that seen following the initial exposure. The secondary reaction associated with re-challenge may either reproduce the features associated with the primary challenge, or may lead to worsening of the condition that was provoked or induced by the initial exposure.
During the course of our clinical investigation we have observed that some children who received a second dose of MMR, or boosting with the combined measles rubella (MR) vaccine, experienced further deterioration in their physical and/or behavioural symptoms following re-exposure. In a report of April 2001, the Vaccine Safety Committee of the US Institute of Medicine (IOM) stated that, in the context of MMR vaccine as a possible cause of this syndrome, “challenge re-challenge exposed would constitute strong evidence of an association”[1].
In the context of adverse vaccine reactions, a biological gradient refers to an increasing severity of, or increased risk of developing, a particular disease outcome. More severe bowel disease in children with regressive autism who had received more than one MMR/MR would be an example of this.
We have undertaken systematic evaluation of re-challenge and biological gradient effects in children with regressive autism who have undergone investigation at the Royal Free Hospital.
“Exposed” – children with normal early development & regressive autism who had received more than one MMR/MR – were compared with age and sex matched “unexposed” – children with normal early development & with regressive autism who had received only one MMR but otherwise similar baseline characteristics to the exposed group. Comparisons included: secondary (2o) developmental/behavioural regression; 2o physical deterioration, prospective, observer-blinded scores of endoscopic & microscopic disease severity.
In a preliminary analysis exposed children scored significantly higher than unexposed children for:
(i) secondary regression on the basis of analyses performed at the different levels, including :
q parental history
q excluding those whose secondary regression occurred following publication of the 1st suggested MMR-autism link in 1998; and,
q inclusion of only those for whom independent corroborative evidence of secondary regression was obtained from the records;
(ii) secondary physical symptoms;
(iii) presence of severe ileal lymphoid hyperplasia; and,
(iii) presence and severity of acute mucosal inflammation.
No measures of disease were worse in unexposed than exposed children.
These data identify a re-challenge effect on symptoms and a biological gradient effect on severity of intestinal inflammation that provide evidence of a causal association between MMR and regressive autism in these children.
I have repeatedly requested a meeting with Sir Liam Donaldson the UK’s Chief Medical Officer to discuss the situation. His response has been to refuse to meet, but instead to demand that we send him the children’s samples. He has provided absolutely no indication, in terms of scientific protocol, how he would proceed to analyse these samples. He has, as far as I am aware, no ethical approval for analysing these samples. He may be reassured to know that independent testing is being conducted and that as part of the litigation process in the UK, the Defendants are being provided with identical samples for independent analysis.
The last seven days have seen a report, in the journal Clinical Evidence, publicised as “new research” disproving any links between autism and the MMR vaccine. The authors specifically excluded clinical research into bowel disease, immune disorders and other documented features of autism that may relate to a viral cause. They do not cite any of our publications beyond the initial study of 12 children in 1998. In fact, the Clinical Evidence paper was no more than a review of the epidemiological studies, including the Davis study that will be critically reviewed during this hearing, that have already been dismissed as irrelevant by an independent review commissioned by the Institute of Medicine in the US.
Key Publications by Wakefield/O’Leary groups
1. Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M, et al. Ileal LNH, non-specific colitis and pervasive developmental disorder in children. Lancet 1997; 351: 637-641.
2. Wakefield AJ, Anthony A, Murch SH, Thomson M, Montgomery SM, Davies S, et al. Enterocolitis in children with developmental disorder. American Journal of Gastroenterology 2000; 95:2285-2295
3. Furlano RI, Anthony A, Day R, Brown A, McGavery L, Thomson MA, et al. Colonic CD8 and ?d T cell infiltration with epithelial damage in children with autism. Journal of Pediatrics 2001;138:366-372
4. Torrente F, Machado N, Ashwood P, et al. Enteropathy with T cell infiltration and epithelial IgG deposition in autism. Molecular Psychiatry 2002;7:375-382
5. Uhlmann V., Martin CM., Shiels O., Pilkington L., Silva I., Lillalea A. Murch SH., Wakefield AJ., O’Leary JJ. Potential viral pathogenic mechanism for new variant inflammatory bowel disease. Molecular Pathology. 2002;55:1-6
6. Kawashima H., Takayuki M., Kashiwagi Y., Takekuma K., Hoshika A., Wakefield AJ. Detection and sequencing of measles virus from peripheral blood mononuclear cells from patients with inflammatory bowel disease and autism. Digestive Diseases and Sciences. 2000;45:723-729
7. Wakefield AJ and Montgomery SM. Measles, mumps, rubella vaccine: through a glass, darkly. Adverse Drug Reactions & Toxicological Reviews 2000;19:265-283.
8. Wakefield AJ and Montgomery SM. Autism, viral infection and measles mumps rubella vaccination. Israeli Medical Association Journal 1999;1:183-187
9. Wakefield AJ, Puleston J., Montgomery SM., Anthony A., O’Leary JJ., Murch SH. Review article: the concept of entero-colonic encephalopathy, autism and opioid receptor ligands. Alimentary Pharmacology and Therapeutics 2002; 16: 663-674
10. Shiels O., Smyth P., Martin C., O’Leary JJ. Development of an allelic discrimination type assay to differentiate between strain origins of measles virus detected in intestinal tissue of children with ileocolonic lymphonodular hyperplasia and concomitant developmental disorder. Pathological Society of Great Britain and Ireland. Journal of Pathology. 2002 .A20
11. Wakefield AJ, Anthony A. Clinical characteristics of children with autism and entero-colitis comparing recipients of one and more than one measles-containing vaccine (submitted).
Publications by others
1. a. Singh V., Lin S., Yang V. Serological association of measles virus and human herpesvirus-6 with brain autoantibodies in autism. Clinical Immunology and Immunopathology. 1998:89;105-108
2. a. Singh VK. Neuro-immunopathogenesis in Autism. 2001. New Foundations of Biology. Berczi I & Gorczynski RM (eds) Elsevier Science B.V. pp447-458
3. a. Horvath K, Papadimitriou JC, Rabsztyn A, Drachenberg C, Tildon JT. Gastrointestinal abnormalities in children with autism. Journal of Pediatrics 1999; 135: 559-563