Recently, a leading British medical journal, The Lancet, retracted a twelve-year old research paper that claimed a link between the MMR (Measles, Mumps, and Rubella) vaccine and autism. The paper’s publication sparked much controversy in autism research, and its retraction has been even bigger news. The retraction of a scientific publication is a statement of error by a peer-reviewed journal, admitting that the original paper should not have been published due to either fraud and misconduct by the authors, or to unintentional scientific error. How did a paper that has received so much attention in the past 12 years get retracted from a prestigious journal like the Lancet? How does this affect future research in autism?

The Science

Autism is a developmental disorder that affects a person’s ability to communicate and interact with others. Symptoms of autism usually appear before three years of age, and include delayed speech and repetitive behaviors. It is believed that autism has a strong genetic basis, though much research has gone into environmental factors such as diet, environmental contaminants, and vaccines. The recently retracted study was one of the first to examine the link between vaccines and autism. The paper received an unexpected amount of media attention when it was published, and caused concern among parents of young children receiving the MMR vaccine. Public health and medical officials cite this study’s publication and its attention for the decreasing rates of childhood vaccination of MMR, as well as other vaccines.

The 1998 paper was based on data from a study involving 12 children with gastrointestinal abnormalities and previously normal cognitive development. Parents of the children reported behavioral problems within two weeks of MMR vaccination. In the paper, Dr. Andrew Wakefield and authors outlined a theory that children with gastrointestinal diseases may be susceptible to an interaction with the MMR vaccine that causes a regression in cognitive development, resulting in autism spectrum disorder. The study participants underwent extensive testing to determine the cause of the change in development, including colonoscopies, lumbar punctures, blood tests, and diagnostic imaging. The paper suggested a new syndrome that linked the gastrointestinal disease and autism, but stated there is no proof MMR vaccination is related to autism. However, in a press conference after the publication of the paper, Dr. Wakefield, the leading author of the study, stated his opinion that the MMR vaccine should be given in three separate doses, one per year. He believed providing three live viruses in a single dose was potentially harmful to children.

Several leading health agencies in the US and UK undertook further scientific research to examine the relationship between MMR vaccines and autism. The Centers for Disease Control, the National Academy of Science’s Institute of Medicine, and European health agencies’ studies contained much larger amounts of data than Wakefield’s studies, and none of these studies found any correlation between autism and MMR vaccination. One study conducted by the Danish Epidemiology Science Center published in the New England Journal of Medicine contained all Danish children born from 1991-1998 in Denmark – over 537,000 subjects. The investigators compared the vaccinated group of children to the unvaccinated group and found no association between vaccination and autism. Vaccination did not put children more at risk than not vaccinating. Confidence in MMR vaccination subsequently increased, but several parents’ groups are still concerned about the possibility of a link.

The Retraction

Wakefield’s research had a significant impact in the medical and public health world over the first few years after the paper’s publication. Vaccination rates dropped significantly in the US and UK due to the new health scare, causing several outbreaks of measles in areas where vaccinations rates were low. Controversy was further fueled when the UK government declined to offer MMR in separate vaccines, as Dr. Wakefield had recommended. In the US, fears increased about thimerosal, a mercury-containing preservative added to the MMR vaccine, and its potentially toxic effect on child brain development. Thimerosal has been removed from several childhood vaccinations over the past several years. However, a study based on California data showed that the removal of thimerosal did not have an effect on autism rates and there has even been in increase in autism cases in California.

In 2004, controversy over the Wakefield paper resurfaced when journalists investigated the study further and found that several of the parents of the children in the study had been paid by a group of lawyers planning to sue the manufacturers of the MMR vaccine; Wakefield had claimed the children had been referred to his medical practice. In light of this conflict of interest, ten of the thirteen original authors retracted their interpretation of the original data. An interpretation of a study is the authors’ opinion of what the data means. The retraction of the interpretation was significant. The retraction by so many of the authors reiterated that the study was not conclusive evidence of a link between vaccines and autism. However, the authors believed the paper was still important for raising the question about a possible link.

The UK General Medical Council (GMC) began investigating Dr. Wakefield in 2007 for scientific misconduct. The investigations confirmed the fact that some of his study participants had been referred to him by the lawyers’ group. They also uncovered evidence that Dr. Wakefield had paid a few subjects to provide blood samples while at his son’s birthday party. In their final hearing, the GMC found that Dr. Wakefield had acted dishonestly by fabricating data. The GMC also cited gross mistreatment of his study participants, subjecting them to unnecessary colonoscopies and lumbar punctures. On January 28, 2010, the UK General Medical Council’s Fitness to Practice Panel found Dr. Wakefield to have acted unethically regarding this study, and guilty of not disclosing financial ties to the outcomes of the study.

The Lancet retracted the paper following the hearing, defending their decision to not retract the paper sooner due to lack of clear evidence that Dr. Wakefield committed any wrongdoing. Retracting scientific publications is no small matter and happens infrequently. The journal Nature examined this issue in 2007 and found that of over nine million science publications between 1950 and 2004, only 596 were retracted, though they estimate that between 10,000 and 100,000 should have been retracted for various reasons. Identifying and investigating claims of fraudulent data is difficult for journals and must include the cooperation of the scientific institution, study sponsors, and government entities (such as the National Institutes of Health Office of Research Integrity). Possible conflicts of interest need to be examined as well.

Future Research

Despite the conflict surrounding the original paper, Wakefield has continued to campaign his beliefs about the link between autism and vaccines. The retraction of the article may shift attention away from his theory, but some parents and advocacy groups have claimed they will continue to support his theory.

Scientists themselves have already been moving away from further investigating these theories as evidence grows against any link between vaccinations and autism. Many leaders in autism research have acknowledged the theory has fallen out of favor. New studies are focusing on other potential causes, such as parental age at conception and genetic mutations. The causes of autism are myriad and complex, and science will continue to try to understand this disease that affects so many families.

–Megan Lee, Harvard School of Public Health Alumna

For More Information:

New York Times article :
< http://www.nytimes.com/2010/02/03/health/research/03lancet.html?ref=health >

Forbes ScienceBiz article :
< http://blogs.forbes.com/sciencebiz/2010/01/u-k-panel-finds-mmr-vaccine-study-leader-acted-dishonestly-and-irresponsibly/ >

Lancet Retraction :
< http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2960175-7/fulltext >

Immunization safety records :
< http://www.iom.edu/Reports/2004/Immunization-Safety-Review-Vaccines-and-Autism.aspx >

How many scientific papers should be retracted? EMBO journal report. :
< http://www.nature.com/embor/journal/v8/n5/full/7400970.html >

Primary Literature:

K. Madsen et al., A Population-Based Study of Measles, Mumps, and Rubella Vaccination and Autism, New England Journal of Medicine, 347:1477-1482 (November 7, 2002)