Perhaps Andrew Wakefield, MD didn’t realize that his 1998 study erroneously linking vaccinations to autism would ignite a decade long controversy. But he should have. If not for the media frenzy fomented by high profile celebrities, the scientific method might have triumphed long ago. Journalists should know better. Yet given the scope of the damage, any claim of vindication would ring hollow. In the end, science prevailed, but at what cost?

After the United Kingdom General Medical Council (GMC) described the actions of Andrew Wakefield, MD, and two of his colleagues as dishonest and irresponsible, The Lancet, a respected medical journal, did something it has only done 10-15 times in its 186-year history, it fully retracted a study by Wakefield and colleagues from the published record.

In 1998, claiming to have found a possible link between autism and the measles-mumps-rubella (MMR) vaccine, Andrew Wakefield and 13 co-authors ignited a firestorm of controversy. Parents fearing that their children would become autistic, refused to have them vaccinated. Lawyers eager to place blame, filed class action lawsuits. Both sides launched personal attacks.

Too little too late
Five years later, ten of the 13 co-authors disavowed the findings. Last year the U.S. vaccine court ruled against those claiming that there was a link between vaccines and autism. Countless research dollars have been spent on rigorous studies aimed at refuting Wakefield’s findings. Fears over a reemergence of diseases like polio and measles should children go unvaccinated are being realized. And most important, the rate of autism has continued to climb.

The California Department of Developmental Services analyzed data on childhood autism from 1995-2006. The rate of autism at age 3 for children born in 1993 was 0.3 per 1000 births; among children born ten years later the rate was 1.3 per 1000 births; by 2006, 4.5 out of every 1000 children born in 2000 were estimated to have autism.

In an effort to help our readers better understand the controversy surrounding vaccines and autism, excerpts from an article previously published in Feeding Times, a baby gooroo publication follows.

The history behind the controversy
Arthur Allen was one of the first to write about the thimerosal controversy in an August 2002 report published in New York Times Magazine. Allen’s report was followed in June 2005, by a series of articles by Robert Kennedy, Jr. in Rolling Stone and Salon.com, in which Kennedy accused government scientists and their academic colleagues of covering up indisputable evidence of a causal link between thimerosal and autism. That same year, Evidence of Harm: Mercury in Vaccines and the Autism Epidemic, A Medical Controversy by David Kirby was released. One critic described Kirby as “an author subtly influenced by the vaccine paranoia people” and cautioned readers to “beware of books like these because they lead with fear and not knowledge.”

Arthur Allen, in response to the Rolling Stone article by Kennedy stated, “Aside from a June 25 New York Times article that discussed the parallel realities of parents and scientists studying thimerosal, there has been little mainstream media response. Considering that about 9,000 lawsuits of claims have been filed against thimerosal and have the potential to wreck the pharmaceutical industry, the debate has high stakes.”

What is thimerosal?
Thimerosal is an organic compound that contains ethyl mercury. It has been used in vaccines since the 1930s to prevent bacterial and fungal contamination. Thimerosal extends the life of vaccines and allows them to be packaged in multi-dose vials.

Is thimerosal safe?
Thimerosal contains mercury, a toxic metal. Mercury occurs naturally in the environment (air, soil, water). It has been found in fish (particularly long-lived fish such as sharks, tilefish, king mackerel, and swordfish) and in small amounts in animal tissues (humans). Dental fillings often contained Mercury, as did thermometers, and vaccines. If large amounts of mercury accumulate in the body over time, death can occur. The Environmental Protection Agency (EPA) has established tolerance levels for mercury based on studies of methyl mercury. The EPA tolerance level is ten times less than the lowest level calculated to cause harm.

Mercury exists in several forms: metallic mercury, inorganic mercury, and organic mercury (methyl mercury, ethyl mercury, phenyl mercury). Thimerosal contains the organic mercury known as ethyl mercury. Nearly all of the research done on mercury toxicity has focused on the organic methyl mercury. Methyl mercury and ethyl mercury are closely related but they have important differences. Different forms of mercury have different health effects. Methyl mercury has a half life of 50 days and accumulates in the body. Ethyl mercury has a half-life of 7-10 days and is less likely to accumulate in the body. Also, ethyl mercury is converted in the body into inorganic mercury and excreted in the stool.

In 1999, the U.S. Food and Drug Administration (FDA) determined that children receiving all of the routinely recommended childhood vaccines would potentially exceed the Environmental Protection Agency (EPA) tolerance levels for mercury (levels based on studies of methyl mercury). So in the interest of safety and out of concern that misinformation regarding thimerosal would lead to widespread refusal of vaccines, the FDA asked vaccine manufacturers to eliminate or reduce the mercury content of vaccines.

Since 2003, all routinely recommended childhood vaccines have been thimerosal-free. Only one childhood vaccine still contains trace amounts of thimerosal (influenza vaccine). Because thimerosal-containing vaccines produce levels of mercury in adults that are so low, experts do not recommend removal of thimerosal from vaccines intended for use in adults and adolescents.

Manufacturers now bottle vaccines in single-dose containers taking care to ensure that the vaccines are not contaminated in the manufacturing and bottling process. This has increased the cost of vaccines and led to vaccine shortages. However, despite these concerns, public health officials are committed to providing thimerosal-free vaccines.

What is autism?
Autism Spectrum Disorders are a group of developmental disabilities that are caused by an abnormality in the brain. According to the Centers for Disease Control and Prevention (CDC), 2/1000 to 6/1000 children have an Autism Spectrum Disorder (ASD). ASDs range from a severe form, autistic disorder (classic autism) to a mild form, Asperger syndrome. If a child has symptoms of either disorder but does not meet the specific criteria of either, he/she is diagnosed with pervasive developmental disorder not otherwise specified (PPD-NOS).

Classic autism affects verbal and nonverbal communication and social interaction. It is usually evident before age three, and can negatively affects educational performance. Characteristics of autism include irregularities and impairments in communication, engagement in repetitive activities and stereotyped movements, resistance to environmental change or change in daily routines, and unusual responses to sensory experiences.

What causes autism?
Genetics is thought to play a key role in the development of autism. Using a broad definition of autism, when one twin has autism, approximately 92% of identical and 10% of fraternal twins have autism, suggesting that autism has a genetic component.

Home movie studies provide some of the best data on when symptoms of autism first appear. In one particular study, home movies were taken of children who eventually were diagnosed with autism and children who were not diagnosed with autism. The movies were made before the children received the MMR vaccine. Neurodevelopment specialists viewed the movies and were consistently able to separate autistic from non-autistic children at one year of age. Using sophisticated movement analysis, movies of children eventually diagnosed with autism and children 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 at 2-3 months of age. These data clearly show that subtle symptoms of autism are present in early infancy and argue against vaccines as a cause of autism.

Some evidence suggests that autism occurs as a result of in utero events such as viral infection. Children exposed to thalidomide during the first or early second trimester were found to have an increased incidence of autism. Autism has been observed in children with ear, but not arm or leg abnormalities. Because arms and legs develop after 24 days’ gestation, it was concluded that the risk period for autism following receipt of thalidomide must be before 24 days’ gestation.

Researchers have also reported an increased risk for autism in children with congenital rubella syndrome and tuberous sclerosis, suggesting that autism involves abnormalities of the central nervous system that occur in utero.

Scientists at the University of California Davis’ M.I.N.D. Institute are investigating whether environmental exposure to chemicals, pesticides, and metals during pregnancy can lead to autism.

Do vaccines cause autism?
The controversy surrounding vaccines and autism dates back to 1998 with the publication of the now retracted paper by Andrew Wakefield titled, “Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children.” The authors theorized that the measles-mumps-rubella (MMR) vaccine causes a series of events that result in the development of autism. The study describes 12 children with neurodevelopmental delay (8 with autism). The author notes that each of the 8 autistic children was diagnosed with autism within 1 month of receiving the MMR vaccine.

Significant flaws found in study
Critics argued that the MMR vaccine is administered to nearly all children at a time when many children are diagnosed with autism. Therefore the observation that some children with autism recently received the MMR vaccine is expected. In addition, only vaccinated children were included in the Wakefield study. To determine whether the MMR vaccine causes autism, both vaccinated and unvaccinated children must be studied. Furthermore, in each of the 8 autistic children, symptoms of autism were observed before, not after, the presence of gastrointestinal symptoms, thus refuting the authors’ claim that autism is a consequence of gastrointestinal inflammation. Wakefield published a second paper in 2002, in which he examined the relationship between the measles virus and autism. Again critics cited a number of flaws.

While the two studies by Wakefield suggest a causal link between the MMR vaccine and autism, five additional studies conclude the opposite. Researchers found no difference in the age of diagnosis of autism in vaccinated and unvaccinated children; the onset of regressive symptoms of autism did not occur within 2, 4, or 6 months of receiving the MMR vaccine; and despite a dramatic increase in the number of reported cases of autism, the percentage of children that have received the MMR vaccine has remained the same. Data from a Danish study show that rates of autism continued to rise despite the removal of thimerosal from all vaccines in 1992.

The result of a critical review of the data was also published in Pediatrics in 2004. Twelve publications met the selection criteria, 10 epidemiologic studies and 2 pharmacokinetic studies. The authors concluded that the data did not support the claim that thimerosal-containing vaccines cause autism.

No link between thimerosal-containing vaccines and autism
In 2000, in response to a request from the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH), the Institute of Medicine (IOM) established an independent expert committee to evaluate the data and determine whether vaccines cause specific health problems.

The Immunization Safety Review Committee published a series of reports between 2001 and 2004. The committee concluded that neither thimerosal-containing vaccines nor the MMR vaccine is associated with autism.

A second IOM committee met in February 2005, composed of different scientists. According to Committee Chair John C. Bailar III, “concerns about access and transparency have accompanied the development and functioning of the Vaccine Safety Datalink data-sharing program, and consequently some people’s trust in the reliability of findings from VSD studies has eroded. Taking steps to improve the independence, transparency, and fairness of VSD procedures will help enhance confidence in the data sharing program and in research based on this important tool for evaluating vaccine safety.”

The Vaccine Safety Datalink is a large, linked database of patient information that was developed jointly by CDC and several private managed care organizations in 1991. It includes data on vaccination histories, health outcomes, and characteristics of more than 7 million patients from eight participating health organizations. Researchers from the CDC and the managed care groups have used VSD information to study whether health problems are associated with vaccinations. The subsequent VSD data-sharing program was launched in 2002 to allow independent, external researchers access to information in the database.

Are vaccines safe?
Vaccines have significantly reduced, and in some cases eliminated, many childhood diseases. In the past, polio, rubella, measles, diphtheria, tetanus, chickenpox, and pertussis (whooping cough) were among the diseases that caused thousands of deaths each year. Today, as a result of immunizations, these diseases rarely occur. A widespread decline in immunizations would lead to outbreaks of serious diseases that now occur rarely.

Any discussion of vaccine safety must include a discussion of the benefits of immunizations as well as the risks. All vaccines have possible side effects. Most side effects are mild and include fever, rash, and tenderness or swelling at the injection site. Some side effects can be severe. For example, the pertussis vaccine can cause persistent crying, high fever, and seizures. While these side effects seldom cause permanent damage, they can be frightening for parents. But if you compare the potential risks of vaccines and the established risks of disease, vaccines, with few exceptions, are the safer choice for both children and adults.

What parents need to know
• Few things in medicine work 100% of the time.

• Few things in medicine are risk-free.

• Researchers are working continually to improve the safety of immunizations.

• A decline in immunization rates will lead to an increase in disease.

To illustrate this fact: In 1974, when 80 percent of Japanese children were vaccinated for pertussis (whooping cough), only 393 cases of pertussis occurred and none of the victims died. The following year information was circulated that the pertussis vaccine was no longer needed and that is was unsafe. By 1976 only 10 percent of Japanese infants were vaccinated and in 1979 over 13,000 cases of whooping cough were reported along with 41 deaths. These are the risk/benefit ratios that parents as well as professionals must consider.

• The only time it is safe to stop giving immunizations is when a disease has been eradicated worldwide.

Only a parent of an autistic child can fully understand the anguish that comes from not knowing autism’s cause. But no amount of fear or frustration justify an abandonment of science.

Bibliography for reference

1. Dales L, et al. Time trends in autism and in MMR immunization coverage in California. JAMA 2001;285:1183-1185.

2. Kaye JA, del Mar 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(7284):460-3.

3. Madsen KM, Hviid A, Vestergaard M, Schendel D, Wohlfahrt J, Thorsen P, et al. A population-based study of measles, mumps, and rubella vaccination and autism. N Eng J Med 2002;347(19):1477-82.

4. 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(3 Pt 1):500-4.

5. Parker SK, Schwartz B, Todd J, Pickering LK. Thimerosal-containing vaccines and autistic spectrum disorder: a critical review of published original data. Pediatrics 2004;114(3):793-804.

6. Stromland K, et al. Autism in thalidomide embropathy: a population study. Devel Med Child Neurol 1994;36:351-356.

7. Taylor B, Miller E, Lingam R, Andrews N, Simmons A, Stowe J. Measles, mumps, and rubella vaccination and bowel problems or developmental regression in children with autism: population study. BMJ 2002;324(7334):393-6.

8. Taylor B, et al. Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association. Lancet 1999;353:2026-2029.

9. Uhlmann V, et al. Potential viral pathogenic mechanism for new variant inflammatory bowel disease. Journal of Clinical Pathology: Molecular Pathology 2002;55:1-6.

10. Wakefield AJ, et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 1998;351:637-641.