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. 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. 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.
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., 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. 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. 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, as did Gupta in a review of possible treatments for autism. 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. 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.” 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.)
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.
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.,
In 2004, then-editor Dr. Richard Horton of the Lancet wrote that Wakefield should had revealed to the journal that he had been paid by attorneys seeking to file lawsuits against vaccine manufacturers. In television interviews, Horton claimed that Wakefield’s research was “fatally flawed.” Most of the co-authors of the study retracted the interpretation in the paper, and in 2010, The Lancet formally retracted the paper itself.
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.
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.
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.
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.)
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.
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. 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. Since then, evidence from many studies has continued to support rejecting an association between thimerosal and autism., 
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.
After thimerosal was removed from most vaccines, autism rates did not drop. Rather, they continued to rise. 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. 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.
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.,
- Centers for Disease Control and Prevention. Autism Spectrum Disorder: Data & Statistics. Accessed 01/25/2018.
- Rice, C.E., Rosanoff, M., Dawson, G., Durkin, M., Croen, L.A., Singer, A., Yeargin-Allsopp, M. Evaluating changes in the prevalence of the autism spectrum disorders (ASDs).Public Health Reviews. 2012; 34(2): 1.
- Hertz-Picciotto, I., Delwiche, L. The rise in autism and the role of age at diagnosis. Epidemiology. 2009; 20(1): 84.
- CDC. Autism spectrum disorder (ASD). Research. Accessed 01/25/2018.
- National Institutes of Health. National Institute of Neurological Disorders and Stroke. Autism spectrum disorder fact sheet. Accessed 01/25/2018.
- Immunization Safety Review Committee, Institute of Medicine. Immunization safety review: vaccines and autism. National Academies Press, 2004. Accessed 01/25/2018.
- Thompson, N.P., Pounder, R.E., Wakefield, A.J., & Montgomery, S.M. Is measles vaccination a risk factor for inflammatory bowel disease? The Lancet. 1995; 345(8957): 1071-1074.
- Fudenberg, H.H. Dialysable lymphocyte extract (DLyE) in infantile onset autism: a pilot study. Biotherapy. 1996; 9(1-3): 143-147.
- Gupta, S. Immunology and immunologic treatment of autism. Proc Natl Autism Assn Chicago.1996;455–460
- Wakefield A, et al. RETRACTED:—Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet. 1998; 351(9103): 637-641.
- Deer, B. Royal free facilitates attack on MMR in medical school single shots videotape. No date. Accessed 01/25/2018.
- Deer, B. Revealed: Wakefield’s secret first MMR patent claims “safer measles vaccine.” No date. Accessed 01/25/2018.
- Offit, P.A. Autism’s False Profits. New York: Columbia University Press; 2008. See Chapters 2 and 3.
- See a list of such studies in this Children’s Hospital of Philadelphia Vaccine Education Center document.
- Horton, R. A statement by the editors of The Lancet. The Lancet. 2004; 363(9411): 820-821.
- Laurance, J. How was the MMR scare sustained for so long when the evidence showed that it was unfounded? The Independent. September 19, 2004. Accessed 01/25/2018.
- Murch, S.H., Anthony, A., Casson, D.H., Malik, M., Berelowitz, M., Dhillon, A.P., ... Walker-Smith, J.A. Retraction of an interpretation. Lancet. 2004; 363(9411): 750.
- The Editors of The Lancet. Comment: RETRACTION:—Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. The Lancet. 2010; 375(9713): 445. Accessed 01/25/2018.
- Meikle, J., Boseley, S. MMR row doctor Andrew Wakefield struck off register. May 24, 2010. Accessed 01/25/2018.
- Deer, B. How the case against the MMR vaccine was fixed. BMJ. 2011; 342: c5347. Accessed 01/25/2018.
- Godlee, F., Smith, J., Marcovitch, H. Wakefield’s article linking MMR vaccine and autism was fraudulent. BMJ. 2011; 342: c7452. Accessed 01/25/2018.
- World Health Organization. Thimerosal in vaccines. July 2006. Accessed 01/25/2018.
- Most of this narrative refers to the facts and chronology outlined in the Food and Drug Administration’s Publication Thimerosal in Vaccines.
- Immunization Safety Review Committee, Institute of Medicine. (2001). Immunization safety review: measles-mumps-rubella vaccine and autism. National Academies Press. Accessed 01/25/2018.
- CDC. Science summary: CDC studies on vaccines and autism. Accessed 01/25/2018.
- American Academy of Pediatrics. Vaccine safety: examine the evidence. (122KB). Updated April 2013. Accessed 01/25/2018.
- DeStefano, F., Price, C.S., Weintraub, E.S. Increasing exposure to antibody-stimulating proteins and polysaccharides in vaccines is not associated with risk of autism. The Journal of Pediatrics. 2013; 163(2): 561-567.
- Children’s Hospital of Philadelphia. Vaccine Education Center. Vaccines ingredients: Aluminum. Accessed 01/25/2018.
- CDC. Autism spectrum disorder (ASD). Research. Accessed 01/25/2018.
- National Institutes of Health. National Institute of Neurological Disorders and Stroke. Autism spectrum disorder fact sheet. Accessed 01/25/2018.
Last update 25 January 2018
What happened to little, red-haired Hannah Poling is hardly unique in the world of autism. She had an uneventful birth; she seemed to be developing normally smiling, babbling, engaging in imaginative play, speaking about 20 words by 19 months. And then, right after receiving a bunch of vaccines, she fell ill and it all stopped. Hannah, now 9, recovered from her acute illness but she lost her words, her eye contact and, in a matter of months, began exhibiting the repetitive behaviors and social withdrawal that typify autism. "Something happened after the vaccines," says her mom, Terry Poling, who is a registered nurse and an attorney. "She just deteriorated and never came back."
Parents of kids like Hannah have been fingering vaccines and, in particular, the mercury-based vaccine preservative thimerosal as a cause of autism for over a decade, but researchers have repeatedly failed to find a link.
What's unique about Hannah's case is that for the first time federal authorities have conceded a connection between her autistic symptoms and the vaccines she received, though the connection is by no means simple. A panel of medical evaluators at the Department of Health and Human Services concluded that Hannah had been injured by vaccines and recommended that her family be compensated for the injuries. The panel said that Hannah had an underlying cellular disorder that was aggravated by the vaccines, causing brain damage with features of autism spectrum disorder (ASD).
A special federal vaccine court has yet to award damages, but the recommendation, made public last week, is causing a sensation in the autism advocacy community. The Polings, who live in Athens, Ga., were originally part of a group of nearly 5,000 families with autistic children seeking damages through the National Vaccine Injury Compensation Program. The other cases remain before the court.
The Poling case is also causing deep concern among public health officials, eager to reassure parents that vaccines are safe and, indeed, hugely beneficial. In a public statement on Friday, Dr. Julie Gerberding, director of the Centers for Disease Control and Prevention (CDC), insisted that "the government has made absolutely no statement about indicating that vaccines are the cause of autism, as this would be a complete mischaracterization of any of the science that we have at our disposal today."
Gerberding and other health authorities point out that the benefits of vaccines far exceed their risks. They also note that thimerosal was eliminated from routinely administered childhood vaccines manufactured after 2001, and yet autism rates have continued to climb. The current CDC estimate is that 1 of 150 American children has an autism spectrum disorder.
Nonetheless, there's no denying that the court's decision to award damages to the Poling family puts a chink a question mark in what had been an unqualified defense of vaccine safety with regard to autism. If Hannah Poling had an underlying condition that made her vulnerable to being harmed by vaccines, it stands to reason that other children might also have such vulnerabilities.
But there are circumstances that make Hannah's case a bit unusual. For one thing, she received an unusually large number of vaccines in 2000 (when thimerosal was still in use). Because of a series of ear infections, Hannah had fallen behind in the vaccine schedule, so in a single day she was given five inoculations covering a total of nine diseases: measles, mumps, rubella, polio, varicella, diphtheria, pertussis, tetanus, and Haemophilus influenzae. "That was just too many vaccines," says Terry Poling. "I didn't find out for several months that they had thimerosal, which contains mercury, a powerful neurotoxin. Had I known, I never would have allowed it to be injected into my child."
Another confounding issue in Hannah's case is the finding that she suffers from a mitochondrial disorder a dysfunction in basic cell metabolism. Mitochondria serve as power generators for each cell in the body, converting food and oxygen into energy. There are a wide range of these disorders, causing symptoms that vary widely but can include muscle weakness, cardiac or liver disease, diabetes, developmental delays and susceptibility to infection. In Hannah's case, the vaccine court determined that the underlying dysfunction of her mitochondria put her at an increased risk of injury from vaccines.
That decision, however, comes as a surprise to experts on mitochondrial disorders. In response to the Poling case, the United Mitochondrial Disease Foundation has released a statement saying, "There are no scientific studies documenting that childhood vaccinations cause mitochondrial diseases or worsen mitochondrial disease symptoms."
Dr. John Shoffner, the Atlanta-based neurologist who identified Hannah Poling's mitochondrial disorder, is "genuinely puzzled" by the court's judgment. Shoffner, who has been studying and treating these disorders for 20 years, says it's impossible to say whether Hannah's mitochondrial disorder was, in fact, a pre-existing condition that set the stage for her autism (as the government contends) or if it developed along with her autism. A specialist in mitochondrial disorders, he is investigating the relationship between autism and these disorders and plans to present a paper on the topic at the annual meeting of the American Academy of Neurology in April. "In some subset of people with ASD a small group of patients, I think mitochondrial dysfunction is an important part of their disease. But it's too early to say whether it gets the ball rolling or if it comes about after the ball got rolling."
Experts on autism spectrum disorders believe that most cases are caused by a combination of genetic vulnerabilities and environmental factors. There may be hundreds of roads to autism, involving numerous combinations of genes and external factors.
Could thimerosal or some other aspect of vaccines be one of these factors? "It's always possible that there's a small subset of kids that have this vulnerability," says Dr. Isaac Pessah, director of the Center for Children's Environmental Health and Disease Prevention at the University of California, Davis. Pessah's lab is looking at dozens of possible environmental factors, including pesticides, plastics and flame-retardants. "This is a very emotional debate," he says, "and we need more research directed at these questions."
It's difficult to draw any clear lessons from the case of Hannah Poling, other than the dire need for more research. One plausible conclusion is that pediatricians should avoid giving small children a large number of vaccines at once, even if they are thimerosal-free. Young children have an immature immune system that's ill-equipped to handle an overload, says Dr. Judy Van de Water, an immunologist who works with Pessah at U.C. Davis. "Some vaccines, such as those aimed at viral infections, are designed to ramp up the immune system at warp speed," she says. "They are designed to mimic the infection. So you can imagine getting nine at one time, how sick you could be." In addition, she says, there's some evidence, that children who develop autism may have immune systems that are particularly slow to mature.
Van de Water worries that current vaccine schedules may be overly aggressive for some children. She suggests that parents who are concerned about vaccine safety ask their pediatricians to give fewer at a time. And, she adds, don't vaccinate a child when he or she is ill.
Hannah Poling is now a third grader in public school, working one-on-one with teachers in a special-ed classroom. She continues to struggle with the effects of autism and also has seizures. Her parents are hoping her case will spur additional research into the causes of autism, including the roles of vaccines and mitochondrial disorders.
"My daughter's case raises more questions than it answers," concedes her father, Dr. Jon Poling, a neurologist who also has a Ph.D. in biophysics. Poling believes in the importance of vaccinating children: "Vaccines are one of the most important advances in the history of medicine," he says, "but people need to know there is a risk to every medicine. There may be a small percentage of people who are susceptible to injury." He and his wife would like to see thimerosal eliminated from flu vaccines, which continue to be given to children and pregnant women, a fact that, he thinks, could be one reason autism rates haven't declined. And he urges pediatricians to take a hard look at the schedule on which vaccines are given. "I think we need a grassroots movement among pediatricians to be more conservative, and not give so many shots at once."