Autism rates in developing countries have risen remarkably in the past 20 years. For children born in 1992, according to the U.S. CDC, about 1 in 150 would be diagnosed with an autism spectrum disorder (ASD). For children born in 2004, about 1 in 68 children would receive an ASD diagnosis.[1] It is difficult to compare autism rates from the 1990s and later with rates from the 1940s through the 1980s: in earlier years, autism was associated primarily with very severely affected individuals and the rate of autism was estimated to be only about 1 in 10,000 people.[2] Beginning in the 1990s, our understanding of the spectrum of autism has expanded greatly, and now individuals who would most likely previously not have been thought of as having autism may be classified with one of a variety of ASDs.[3]

Whether the high rates of autism today are due to increased diagnosis and reporting, changing definitions of autism, or an actual increase in development of ASD is unknown.[4],[5] Regardless, researchers and worried parents alike have speculated about causes of autism, and the issue has been widely studied. The role of vaccines has been questioned, along with other possible risk factors for ASD, such as genetic predisposition, advanced parental age, and other environmental factors. Vaccines have perhaps received more scrutiny that any other speculated cause of ASD, and the great majority of scientists, physicians, and public health researchers have come to the conclusion that there is no association between vaccines and autism.[6] Some, however, still question whether vaccines play a role in ASD development, and so the public health and medical establishments continue to address these concerns.

The MMR Hypothesis

The story of how vaccines came to be questioned as a cause of autism dates back to the 1990s. In 1995, a group of British researchers published a cohort study in the Lancet showing that individuals who had been vaccinated with the measles-mumps-rubella vaccine (MMR) were more likely to have bowel disease than individuals who had not received MMR.[7] One of these researchers was gastroenterologist Andrew Wakefield, MD, who went on to further study a possible link between the vaccine and bowel disease by speculating that persistent infection with vaccine virus caused disruption of the intestinal tissue that in turn led to bowel disease and neuropsychiatric disease (specifically, autism). Part of this hypothesis – that vaccination was associated with autism – had been suggested previously a few researchers. For example, Fudenberg, in a small pilot study published in a non-mainstream journal, posited this relationship[8], as did Gupta in a review of possible treatments for autism.[9] This hypothesis had not been systematically investigated when Wakefield began to interrogate it.

In 1998, Wakefield, along with 12 co-authors, published a case series study in the Lancet claiming that they found evidence, in many of the 12 cases they studied, of measles virus in the digestive systems of children who had exhibited autism symptoms after MMR vaccination.[10] Though in the paper they stated that they could not demonstrate a causal relationship between MMR vaccination and autism, Wakefield suggested in a video released to coincide with the paper’s publication that a causal relationship existed between the MMR and autism: “…the risk of this particular syndrome [what Wakefield termed autistic enterocolitis] developing is related to the combined vaccine, the MMR, rather than the single vaccines.”[11] He then recommended that the combination MMR vaccine be suspended in favor of single-antigen vaccinations given separately over time. (Wakefield himself had filed for a patent for a single-antigen measles vaccine in 1997 and so would seem to have a potential financial interest in promoting this view.[12])

Reaction to the Wakefield publication was immediate. Press outlets covered the news widely and frightened parents began to delay or completely refuse vaccination for their children, both in Britain and the United States. MMR vaccination rates in Britain plummeted.[13]

Over the next twelve years, the possibility of a link between MMR and autism was studied exhaustively. No reputable, relevant study confirmed Wakefield’s findings; instead, many well-designed studies have found no link between MMR and bowel disease or MMR and autism.[6],[14]

In 2004, then-editor Dr. Richard Horton of the Lancet wrote that Wakefield should have revealed to the journal that he had been paid by attorneys seeking to file lawsuits against vaccine manufacturers.[15] In television interviews, Horton claimed that Wakefield’s research was “fatally flawed.”[16] Most of the co-authors of the study retracted the interpretation in the paper[17], and in 2010, The Lancet formally retracted the paper itself.[18]

Three months after the retraction, in May 2010, Britain’s General Medical Council banned Wakefield from practicing medicine in Britain, stating that he had shown “callous disregard” for children in the course of his research. The council also cited previously uncovered information about the extent to which Wakefield’s research was funded by lawyers hoping to sue vaccine manufacturers on behalf of parents of children with autism.[19]

On January 6, 2011, the BMJ published a report by Brian Deer, a British journalist who had previously reported on flaws in Wakefield’s work. For this new report, Deer spoke with parents of children from the retracted study and found evidence that Wakefield committed research fraud by falsifying data about the children’s conditions.[20]

Specifically, Deer reported that while the paper claimed that eight of the study’s twelve children showed either gastrointestinal or autism-like symptoms days after vaccination, records instead show that at most two children experienced these symptoms in this time frame. Additionally, while the paper claimed that all twelve of the children were “previously normal” before vaccination with MMR, at least two had developmental delays that were noted in their records before the vaccination took place.

After examining the records for all twelve children, Deer noted that the statements made in the paper did not match numbers from the records in any category: the children having regressive autism; those with non-specific colitis; or those showing first symptoms within days after receiving the MMR vaccine. The Lancet paper claimed that six of the children had all three of these conditions; according to the records, not a single child actually did. (See a table entitled “Comparison of three features of the 12 children in The Lancet paper with features apparent in the NHS records, including those from the Royal Free hospital” that breaks down the comparison between the Lancet numbers and the medical records in the Deer article here.)

In an accompanying editorial, BMJ editor in chief Fiona Godlee and co-authors Jane Smith and Harvey Marcovitch examine the damage to public health caused by a tiny study based on parental recall with no control group – a study that turned out to be almost entirely fraudulent, but whose impact continues to this day.[21]

Although the findings of Wakefield’s paper have long been discredited by scientists, the evidence that the data itself was falsified makes this report by the BMJ a landmark moment in the history of vaccines. Evidence is strong that the original study should not have been published not merely because it was poorly conducted, but also because it was a product of research fraud.

The Thimerosal Hypothesis

MMR is not the only vaccine or vaccine component that has been targeted for scrutiny by those who suspect vaccination might be related to autism. After the MMR controversy died down, critics turned their questions to thimerosal, a mercury-containing preservative used in some vaccines. (Thimerosal had never been used in MMR, as antimicrobial agents are not used in live vaccines.[22])

In the late 1990s lawmakers, environmentalists, and medical and public health workers became concerned about environmental exposures to mercury, particularly from consumption of fish. With heightened attention to known and potential harmful effects of such exposures, the U.S. Food and Drug Administration (FDA) in 1999 requested that drug companies report on amounts of mercury in their products. The results for mercury in vaccines, in the form of thimerosal, exceeded FDA guidelines for exposures to the kind of mercury found in fish. Mercury in fish appears in the form of methylmercury, which is not readily metabolized and excreted in the human body. It is known to cause, at certain levels of high exposure, harmful neurological effects. The mercury in thimerosal metabolizes in the body to ethylmercury, a compound that, while not widely studied at the time, was thought to be much less harmful than methylmercury.[23]

The FDA had a dilemma: there were no recommendations for exposure to levels of ethylmercury. Should they apply the methylmercury guidelines to ethylmercury? Was there cause for concern about exposure to mercury in childhood vaccines? Unable to answer these questions immediately, together with the American Academy of Pediatrics and other groups, they called for vaccine companies to reduce or eliminate the use of thimerosal in vaccines. Additionally, studies were planned to investigate whether there were harmful effects in children exposed to the amount of mercury in vaccines.

Activists and others became concerned about the safety of thimerosal at this point, and they posited that autism could be an outcome of exposure to mercury in vaccines. The Institute of Medicine undertook a comprehensive safety review of the issue. Their preliminary report, published in 2001, stated that the committee did not find enough evidence to support or reject a causal relationship between mercury in vaccines and neurodevelopmental disorders.[24] However, their final report, published in 2004, came to the conclusion that the large body of evidence gathered on the question since 2001 favored rejecting the hypothesis that mercury in vaccines was associated with neurodevelopmental disorders.[6] Since then, evidence from many studies has continued to support rejecting an association between thimerosal and autism.[25], [26]

Today, thimerosal is no longer used in most childhood vaccines, though some forms of influenza vaccine available in multi-dose vials may contain the preservative.[23]

Other Hypotheses

After thimerosal was removed from most vaccines, autism rates did not drop. Rather, they continued to rise.[1] Some vaccine critics shifted their attention from a hypothesized mercury exposure/autism connection to other targets. One such target is the number of vaccines given to children. Many vaccines have been added to the childhood immunization schedule since the 1980s, and some critics have voiced concern that this increase in vaccine exposure results in autism. However, no evidence of an association between increased exposure to vaccines and autism has appeared.[27] Others have focused on the aluminum adjuvant in some vaccines as a potential cause of autism. Yet the amounts of aluminum used in vaccines are small in comparison to other exposures to aluminum, such as in breast milk and infant formula. Aluminum in vaccines has not been implicated in any infant or childhood health problems.[28]

Conclusion

Most scientific and medical experts are satisfied that no connection exists between vaccines and autism and other neurodevelopmental disorders. Still, critics continue to question the issue. Not only do they question the relationship between MMR and thimerosal and autism, they bring up further culprits they believe might play a role in development of autism. Researchers continue to examine these questions, but there is no evidence that these factors play a role in autism development. Most autism researchers hold that the causes of autism are many and include genetic and environmental factors, but do not involve vaccines.[4],[5]

Sources

Last update 25 January 2018