Two studies have been cited by those claiming that the MMR vaccine causes autism. Both studies are critically flawed.
In 1998, Andrew Wakefield and colleagues published a paper in the journal Lancet. Wakefield's hypothesis was that the measles, mumps and rubella (MMR) vaccine caused a series of events that include intestinal inflammation, entrance into the bloodstream of proteins harmful to the brain, and consequent development of autism. In support of his hypothesis, Dr. Wakefield described 12 children with developmental delay — eight had autism. All of these children had intestinal complaints and developed autism within one month of receiving MMR.
The Wakefield paper published in 1998 was flawed for two reasons:
- About 90 percent of children in England received MMR at the time this paper was written. Because MMR is administered at a time when many children are diagnosed with autism, it would be expected that most children with autism would have received an MMR vaccine, and that many would have received the vaccine recently. The observation that some children with autism recently received MMR is, therefore, expected. However, determination of whether MMR causes autism is best made by studying the incidence of autism in both vaccinated and unvaccinated children. This wasn't done.
- Although the authors claim that autism is a consequence of intestinal inflammation, intestinal symptoms were observed after, not before, symptoms of autism in all eight cases.
This study was subsequently retracted; in scientific terms, this means that the paper is not part of the scientific record because it was found to be based on scientific misconduct. In this case, the studies were deemed fraudulent and data misrepresented.
In 2002, Wakefield and coworkers published a second paper examining the relationship between measles virus and autism. The authors tested intestinal biopsy samples for the presence of measles virus from children with and without autism. Seventy-five of 91 children with autism were found to have measles virus in intestinal biopsy tissue as compared with only 5 of 70 patients who didn't have autism. On its surface, this was a concerning result. However, the second Wakefield paper was also critically flawed for the following reasons:
- Measles vaccine virus is live and attenuated. After inoculation, the vaccine virus probably replicates (or reproduces itself) about 15 to 20 times. Measles vaccine virus is likely to be taken up by specific cells responsible for virus uptake and presentation to the immune system (termed antigen-presenting cells or APCs). Because all APCs are mobile, and can travel throughout the body (including the intestine), it is plausible that a child immunized with MMR would have measles virus detected in intestinal tissues using a very sensitive assay. To determine if MMR is associated with autism, one must determine if the finding is specific for children with autism. Therefore, children with or without autism must be identical in two ways. First, children with or without autism must be matched for immunization status (i.e., receipt of the MMR vaccine). Second, children must be matched for the length of time between receipt of MMR vaccine and collection of biopsy specimens. Although this information was clearly available to the investigators and critical to their hypothesis, it was specifically omitted from the paper.
- Because natural measles virus is still circulating in England, it would have been important to determine whether the measles virus detected in these samples was natural measles virus or vaccine virus. Although methods are available to distinguish these two types of virus, the authors chose not to use them.
- The method used to detect measles virus in these studies was very sensitive. Laboratories that work with natural measles virus (such as the lab where these studies were performed) are at high risk of getting results that are incorrectly positive. No mention is made in the paper as to how this problem was avoided.
- As is true for all laboratory studies, the person who is performing the test should not know whether the sample is obtained from a case with autism or without autism (blinding). No statements were made in the methods section to assure that blinding occurred.
Several studies have been performed that disprove the notion that MMR causes autism.
Brent Taylor and co-workers
In 1999, Brent Taylor and co-workers examined the relationship between receipt of MMR and development of autism in an excellent, well-controlled study. Taylor examined the records of 498 children with autism or autism-like disorder.
Cases were identified by registers from the North Thames region of England before and after the MMR vaccine was introduced into the United Kingdom in 1988. Taylor then examined the incidence and age at diagnosis of autism in vaccinated and unvaccinated children. He found that:
- The percentage of children vaccinated was the same in children with autism as in other children in the North Thames region.
- No difference in the age of diagnosis of autism was found in vaccinated and unvaccinated children.
- The onset of symptoms of autism did not occur within two, four, or six months of receiving the MMR vaccine.
Madsen and colleagues
One of the best studies was performed by Madsen and colleagues in Denmark between 1991 and 1998 and reported in the New England Journal of Medicine. The study included 537,303 children representing 2,129,864 person-years of study. Approximately 82 percent of children had received the MMR vaccine. The group of children was selected from the Danish Civil Registration System, vaccination status was obtained from the Danish National Board of Health, and children with autism were identified from the Danish Central Register. The risk of autism in the group of vaccinated children was the same as that in unvaccinated children. Furthermore, there was no association between the age at the time of vaccination, the time since vaccination, or the date of vaccination and the development of autism.
Subsequent studies and meta-analysis have corroborated the findings that the MMR vaccine does not cause autism.
Watch as Dr. Offit talks about vaccines and autism in this short video, part of the Talking about Vaccines with Dr. Paul Offit video series.
One of the best ways to determine whether a particular disease or syndrome is genetic is to examine the incidence in identical and fraternal twins. Using a strict definition of autism, approximately 60 percent of identical and 0 percent of fraternal twins have autism. Using a broader definition of autism (i.e. autistic spectrum disorder), approximately 92 percent of identical and 10 percent of fraternal twins have autism. Therefore, autism clearly has a genetic basis.
Clues to the causes of autism can be found in studies examining when the symptoms of autism are first evident. Perhaps the best data examining when symptoms of autism are first evident are the "home-movie studies. These studies took advantage of the fact that many parents take movies of their children during their first birthday (before they have received the MMR vaccine).
Home movies from children who were eventually diagnosed with autism and those who were not diagnosed with autism were coded and shown to developmental specialists. Investigators were, with a very high degree of accuracy, able to separate autistic from non-autistic children at 1 year of age. These studies found that subtle symptoms of autism were present earlier than some parents had suspected, and that receipt of the MMR vaccine did not precede the first symptoms of autism. Other investigators extended the home-movie studies of 1-year-old children to include videotapes of children taken at 2 to 3 months of age.
Timing of first symptoms
Using a sophisticated movement analysis, videos from children eventually diagnosed with autism or not diagnosed with autism were coded and evaluated for their capacity to predict autism. Children who were eventually diagnosed with autism were predicted from movies taken in early infancy. This study supported the hypothesis that very subtle symptoms of autism are present in early infancy and argues strongly against vaccines as a cause of autism.
Structural abnormalities of the nervous system
Toxic or viral insults to the fetus that cause autism, as well as certain central nervous system disorders associated with autism, support the notion that autism is likely to occur in the womb. For example, children exposed to thalidomide during the first or early second trimester were found to have an increased incidence of autism. Thalidomide was a medication that used to be prescribed to pregnant women to treat nausea. However, autism occurred in children with ear, but not arm or leg, abnormalities. Because ears develop before 24 days gestation, and arms and legs develop after 24 days gestation, the risk period for autism following receipt of thalidomide must have been before 24 days gestation. In support of this finding, Rodier and colleagues found evidence for structural abnormalities of the nervous system in children with autism. These abnormalities could only have occurred during development of the nervous system in the womb.
Natural rubella infection
Similarly, children with congenital rubella syndrome are at increased risk for development of autism. Risk is associated with exposure to rubella before birth but not after birth.
The following studies all support the fact that autism occurs during development of the nervous system early in the womb:
- The genetics of autism
- The timing of the first symptoms of autism (home-movie studies)
- The relationship between autism and the receipt of the MMR vaccine
- Structural abnormalities of the nervous system of children with autism
- Thalidomide and natural rubella infection
Unfortunately, for current and future parents of children with autism, the controversy surrounding vaccines has caused attention and resources to focus away from a number of promising leads.
The Autism Science Foundation is a non-profit organization that follows the developments related to autism; in particular, making sure that the studies are scientifically sound. Their website provides up-to-date information about what is known about the causes of autism.
Adrien JL, Faure M, Perrot A, et al. Autism and Family Home Movies: Preliminary Findings. JAutism and Developmental Disorders. 1991; 21:43-49.
Adrien JL, Lenoir P, Martineau J, et al. Blind Ratings of Early Symptoms of Autism Based Upon Family Home Movies. J Am Acad Child Adolesc Psychiatry 1993; 32:617-626.
Adrien JL, Perrot A, Sauvage D, et al. Early Symptoms in Autism From Family Home Movies: Evaluation and Comparison Between 1st and 2nd Year of Life Using I.B.S.E. Scale. ActaPaedopsychiatrica 1992; 55:71-75.
Bailey A, LeCouteur A, Gottesman I, et al. Autism As A Strongly Genetic Disorder: Evidence From A British Twin Study. Psychol Med 1995; 25:63-77.
Bauman M. Autism: Clinical Features and Neurological Observations. Tager-Flusberg H. (ed.) Neurodevelopmental Disorders. Cambridge, MA: The MIT Press, 1999, pp. 383-399.
Bauman M, Kemper T. Neuroanatomic Observations of the Brain in Autism. Bauman M, Kemper T (eds.), The Neurobiology of Autism. Baltimore, MD: The Johns Hopkins University Press, 1997, pp. 119-145.
Chess S, Fernandez P, Korn S. Behavioral Consequences of Congenital Rubella. J Pediatr1978; 93:699-703.
Dales L, Hammer SJ, Smith NJ. Time Trends in Autism and in MMR Immunization Coverage in California. JAMA 2001; 285:1183-1185.
DeStefano, R, Bhasin, TK, et. Al. Age at First Measles-Mumps-Rubella Vaccination in Children With Autism and School-Matched Control Subjects: A Population-Based Study in Metropolitan Atlanta. Pediatrics 2004:113:259-266.
Deykin EY, MacMahon B. Viral exposure and autism. Am J Epidemiol 1979;109:628-638.
Eriksson A, de Chateau P. Brief Report: A Girl Aged Two Years and Seven Months With Autistic Disorder Videotaped From Birth. J Autism and Developmental Disorders 1992; 22:127-129.
Farrington CP, Miller E, Taylor B. MMR and Autism: Further Evidence Against A Causal Association. Vaccine. 2001; 19:3632-3635.
Folstein S, Rutter M. Infantile Autism: A Genetic Study of 21 Twin Pairs. J Child Psychol Psychiatry. 1977; 18:297-321.
Fombonne E, Chakrabarti S. No Evidence for A New Variant of Measles-Mumps-Rubella-Induced Autism. Pediatrics. 2001; 108:e58.
Gerber JS, Offit PA. Vaccines and Autism: A Tale of Shifting Hypotheses. Clin Inf Dis. 2009;48:456-61.Review of subject
Ingram JL, Stodgell CJ, Hyman SL, et al. Discovery of Allelic Variants of HOXA1 and HOXB: Genetic Susceptibility to Autism Spectrum Disorders. Teratology. 2000; 62:393-405.
International Molecular Genetic Study of Autism Consortium (IMGSAC). A Genomewide Screen for Autism: Strong Evidence for Linkage to Chromosomes 2q, 7q, and 16p. Am J Hum Genet. 2001; 69:570-581.
Kaye JA, Melero-Montes M, Jick H. Mumps, Measles, and Rubella Vaccine and the Incidence of Autism Recorded by General Practitioners: A Time Trend Analysis. BMJ. 2001; 322:460-463.
Kemper TL, Bauman M. Neuropathology of Autism. J Neuropathol Exp Neurol. 1998; 57:645-652.
Lijam N, Paylor R, McDonald MP, et al. Social Interaction and Sensorimotor Gating Abnormalities in Mice Lacking Dvl1. Cell. 1997; 90:895-905.
Madsen KM, Hviid A, Vestergaard M, et al. A Population-Based Study of Measles, Mumps, and Rubella Vaccination and Autism. N Engl J Med. 2002; 347:1477-1482.
Makela, A, Nuorti, JP, and Peltola, H. Neurologic Disorders After Measles-Mumps-Rubella Vaccination, Pediatrics. 2002; 110:957-963.
Mars AE, Mauk JE, Dowrick PW. Symptoms of Pervasive Developmental Disorders as Observed in Prediagnostic Home Videos of Infants and Toddlers. J Pediatr .1998; 132:500-504.
Peltola H, Patja, A, et. Al. No Evidence for Measles, Mumps, and Rubella Vaccine-Associated Inflammatory Bowel Disease or Autism in a 14-Year Prospective Study. Lancet. 1998; 351:1327-1328.
Rodier PM. The Early Origins of Autism. Scientific American, February 2000, pp.56-63.
Rodier P, Ingram JL, Tisdale B, et al. Embryological Origin for Autism: Developmental Anomalies of the Cranial Nerve Motor Nuclei. J Comp Neurol. 1996; 370:247-261.
Stokstad E. New Hints into the Biological Basis of Autism. Science. 2001; 294:34-37.
Strvmland K, Nordin V, Miller M, et al. Autism in Thalidomide Embryopathy: A Population Study. Developmental Med Child Neurol. 1994; 36:351-356.
Taylor B, Miller E, Farrington P, et al. Autism and Measles, Mumps, and Rubella Vaccine: No Epidemiologic Evidence for A Causal Association. Lancet. 1999; 353:2026-2029.
Taylor B, Miller E, Lingam, et al. Measles, Mumps, and Rubella Vaccination and Bowel Problems or Developmental Regression in Children with Autism: A Population Study. BMJ. 2002; 324:393-396.
Taylor LE, Swerdfeger AL, Eslick GD. Vaccines are not associated with autism: an evidence-based meta-analysis of case-control and cohort studies. Vaccine. 2014;32(29):3623-3629.
Teitelbaum P, Teitelbaum O, Nye J, et al. Movement Analysis in Infancy May Be Useful for Early Diagnosis of Autism. Proc Natl Acad Sci USA. 1998; 95:13982-13987.
Uhlmann V, Martin CM, Sheils O, et al. Potential Viral Pathogenic Mechanism for New Variant Inflammatory Bowel Disease. J Clin Pathol: Mol Pathol. 2002; 55:84-90.
Wakefield AJ, Murch SH, Anthony A, et al. Ileal-Lymphoid-Nodular Hyperplasia, Non-Specific Colitis, and Pervasive Developmental Disorder in Children. Lancet. 1998; 351:637-641.
Wassink TH, Piven J, Vieland VJ, et al. Evidence Supporting WNT2 as an Autism Susceptibility Gene. Am J Med Gen. 2001; 105:406-413.
Beyond the Autism/Vaccine Hypothesis: What Parents Need to Know about Autism Research
A decade ago most researchers agreed that we needed to study vaccines in relation to autism. We had to reconcile the fact that the number of vaccines children were receiving was increasing, and at the same time, the number of children who were being diagnosed with autism also was on the rise. Fortunately this was a question that could be studied – and answered – by science. We looked at children who received vaccines and those who didn’t, or who received them on a different, slower schedule. There was no difference in their neurological outcomes. Multiple studies have been completed which investigated the measles, mumps and rubella vaccination in relation to autism. Researchers have also studied thimerosal, a mercury-based preservative, to see if it had any relation to autism. The results of studies are very clear; the data show no relationship between vaccines and autism. Read the studies themselves below and browse our recommended reading list.
Making the CASE for Vaccines
Click here to read and download our guide to talking about vaccines.
Read the Science
Literature Reviews: Autism and Vaccines
Autism Occurrence by MMR Vaccine Status Among US Children With Older Siblings With and Without Autism
The Journal of the American Medical Association
Safety of Vaccines Used for Routine Immunization of U.S. Children: A Systematic Review
Vaccines are Not Associated with Autism: An Evidence-Based Meta-Analysis of Case-Control and Cohort Studies
On-time Vaccine Receipt in the First Year Does Not Adversely Affect Neuropsychological Outcomes
Smith, M and Woods, C
Vaccines and Autism: A Tale of Shifting Hypotheses
Clinical Infectious Diseases
Offit, Paul and Gerber, Jeffrey S.
Immunization Safety Review: Vaccines and Autism
Institute of Medicine
Adverse Effects of Pertussis and Rubella Vaccines: A Report of the Committee to Review the Adverse Consequences of Pertussis and Rubella Vaccines
Institute of Medicine
Too Many Too Soon?
Addressing Parents’ Concerns: Do Multiple Vaccines Overwhelm or Weaken the Infant’s Immune System?
Offit, Paul A., Quarles, Jessica, et al.
Immunization Safety Review: Multiple Immunizations and Immune Dysfunction
Institute of Medicine
Cellular Immune Responses in Neonates
International Reviews of Immunology
Fadel S, Sarazotti M.
Neonatal and Early Life Vaccinology
The Problem with Dr. Bob’s Alternative Vaccine Schedule
Offit, Paul A. and Moser, Charlotte A.
Thimerosal and Autism Studies
Neuropsychological performance 10 years after immunization in infancy with thimerosal-containing vaccines.
Tozzi AE, Bisiacchi P, Tarantino V, De Mei B, D’Elia L, Chariotti F, Salmaso S.
Continuing Increases in Autism Reported to California’s Developmental Services System
Archives of General Psychiatry
Robert Schechter, MD, MSc and Judith K. Grether, PhD
Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years
New England Journal of Medicine
Thompson WW, Price C, Goodson B, et al.
Lack of Association Between Rh Status, Rh Immune Globulin in Pregnancy and Autism
American Journal of Medical Genetics
Judith H. Miles and T. Nicole Takahashi
Comparison of Blood and Brain Mercury Levels in Infant Monkeys Exposed to Methylmercury or Vaccines Containing Thimerosal
Environmental Health Perspectives
Thomas M. Burbacher, PhD
Thimerosal Exposure in Infants and Developmental Disorders: A Prospective Cohort Study in the United Kingdom Does Not Support a Causal Association
John Heron and Nick Andrews, PhD and Jean Golding, DSc
Neurotoxic Effects of Postnatal Thimerosal Are Mouse Strain Dependent
M Hornig, M
Safety of Thimerosal-Containing Vaccines: A Two-Phased Study of Computerized Health Maintenance Organization Database
Thomas Verstraeten, MD
Association Between Thimerosal-Containing Vaccine and Autism
Journal of the American Medical Association
Anders Hviid, MSc
Thimerosal and the Occurrence of Autism: Negative Ecological Evidence from Danish Population-Based Data
Kreesten M. Madsen, MD
“Autism and Thimerosal-Containing Vaccines: Lack of Consistent Evidence for an Association”
American Journal of Preventive Medicine
Paul Stehr-Green, DrPh, MPH
Thimerosal and Autism?
Karen Nelson, MD
Mercury concentrations and metabolism in infants receiving vaccines containing thiomersal: A descriptive study
Michael Pichichero, MD
Measles-Mumps-Rubella (MMR) Vaccine and Autism Studies
Examination of the Safety of Pediatric Vaccine Schedules in a Non-Human Primate Model: Assessments of Neurodevelopment, Learning, and Social Behavior
Environmental Health Perspectives
Early Exposure to the Combined Measles-Mumps-Rubella Vaccine and Thimerosal-Containing Vaccines and Risk of Autism Spectrum Disorder
January 3, 2015
Remembering How to Fight Measles
New York Times
Paul A. Offit, MD
How to Think About the Risk of Autism
New York Times
Sam Wang, Ph.D.
Lack of Association Between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study
Hornig M, Briese T, Buie T, Bauman ML, Lauwers G, et al.
Measles Vaccination and Antibody Response in Autism Spectrum Disorders
Archives of Disease in Childhood
Gillian Baird, F.R.C.Paed.
Pervasive Developmental Disorders in Montreal, Quebec, Canada: Prevalence and Links With Immunizations
Eric Fombonne, MD
MMR Vaccination and Pervasive Developmental Disorders: A Case-Control Study
Liam Smeeth, MRCGP
September 11, 2004
Association of Autistic Spectrum Disorder and the Measles, Mumps, and Rubella Vaccine
Archives of Pediatrics & Adolescent Medicine
Kumanan Wilson, MD, MSc, FRCP
Neurologic Disorders After Measles-Mumps-Rubella Vaccination
Annamari Makela, MD
No Evidence for a New Variant of Measles-Mumps-Rubella-Induced Autism
Eric Fombonne, FRCPsych
Autism and Vaccines in the Media
A Journalist’s Guide to Covering Outbreaks of Vaccine-Preventable Disease
From the producers of the PBS-NOVA special “Vaccines—Calling the Shots.”
On January 21st, 2011, Dr. Paul Offit was on The Colbert Report speaking about his new book, “Deadly Choices: How The Anti-Vaccine Movement Threatens Us All.” Click Here to Watch the Interview.
On September 9, 2014, ASF President Alison Singer was on The Leonard Lopate Show to talk about the risks of not vaccinating. Click here to listen to the program.
If we ask the same questions we’ll get the same answers. We’ve asked the autism vaccine question over two dozen times and each time we get the same response: no relationship. We need to move on. We need to invest in studying genetics, the brain structures of children with autism, and environmental factors that may be playing a role.
Below are three fact-sheets prepared by physicians at the Children’s Hospital of Philadelphia. They are excellent resources to distribute at events.
Below are two tables prepared by the initiative Every Child By Two. These tables summarize the major procedures and conclusions of the most recent studies regarding autism and Thimerosal, as well as autism and the MMR vaccine.