Thimerosal, Vaccines, and Autism Spectrum Disorder

Overview of Autism Spectrum Disorders

Autism is one of the most severe and disruptive of all childhood disorders. It is a communicative disorder that interferes with an individual's ability to form social relationships and to communicate with others. Autism Spectrum Disorders (ASDs) officially belong to a group of conditions known as developmental disabilities, characterized by problems with social and communication skills of varying degrees (Schechter & Grether, 2008). Autistic individuals also commonly display unusual ways of learning, reacting to different sensations, and paying attention. Sufferers tend to repeat certain behaviors and have difficulties when required to change their usual daily activities. ASDs are commonly said to start in childhood and last throughout a person's entire life; however, as discussed below, many new theories about the cause or causes of these disorders offer hope for effective treatments (Gerber & Offit, 2010).

Recent reviews in environmental health have suggested that early exposure to hazardous substances may underlie some cases of neurodevelopmental disorders, including ADHD, learning disabilities, and speech and language difficulties (Baker, 2008). In 1999, thimerosal — used as a vaccine preservative — was identified as a widespread source of organic mercury exposure in infants. Mercury (Hg), a heavy metal, is considered highly neurotoxic (Blaxill et al., 2003). The amount of mercury in vaccines, while small, exceeded United States Environmental Protection Agency (USEPA) safety guidelines on a cumulative basis. Certain individuals may exhibit severe adverse reactions to low doses of mercury that are otherwise largely benign to the majority of those exposed. Some individuals with idiopathic autism spectrum disorder may represent such a sensitive population (Nelson & Bauman, 2003).

Thimerosal and Its Chemical Properties

Characteristics of autism are under study in part because of the proposed association between ASD and thimerosal, for several reasons: ASD traits are known to arise from mercury exposure; the onset of ASD symptoms is temporally associated with the administration of immunizations; the reported increase in the prevalence of autism in the 1990s closely follows the introduction of two mercury-containing vaccines; and elevated mercury has been detected in biological samples from autistic patients (Baker, 2008).

Thimerosal (49.55% mercury by weight) is a highly toxic mercury compound used as a preservative in some over-the-counter and prescription drugs, including most flu shots given to pregnant women, infants, children, adults, and the elderly (Downey, 2010). It has been proposed that thimerosal breaks down into ethyl mercury in the body and exposes a thiol group. This group has a high affinity for sulfhydryl groups and readily exchanges to bind with available sulfhydryl groups. Chemically, thimerosal contains an ethyl mercury group that becomes covalently bonded to the sulfhydryl group (Nelson & Bauman, 2003).

On April 19, 2007, Dr. Larry L. Needham, Chief of the Organic Analytical Toxicology Branch at the CDC, announced to the US National Academy of Sciences' Institute of Medicine that thimerosal was among the chemicals linked to ASD. Geier and Geier (2007) subsequently provided the first clinical case series of ASD patients confirming a causal role for thimerosal-preserved drugs in patients with a regressive ASD diagnosis. This clinical study also found a significant dose-response relationship between the severity of ASD symptoms and the total mercury dose these children received from thimerosal-preserved drugs. Initially normally developing children suffered mercury toxic encephalopathy that manifested with clinical symptoms consistent with a regressive ASD diagnosis (Baker, 2008). Mercury poisoning should therefore be considered as a possible cause for children exhibiting ASD symptoms in any differential diagnosis designed to assess underlying causes. A urinary porphyrin profile analysis (UPPA) test can now confirm whether an autistic child is mercury poisoned, and much of this information is readily available through the internet (Kortum, 2008).

Evidence Linking Mercury Exposure to ASD

The plausibility of the thimerosal-autism hypothesis has been questioned repeatedly. In 1999, the US Public Health Service and the American Academy of Pediatrics (AAP) called for the reduction or elimination of the ethyl mercury preservative thimerosal from vaccines, stating that the cumulative amount of mercury in infant vaccines exceeded EPA guidelines for methyl mercury (Dardennes et al., 2011). Since 2002, thimerosal-containing vaccines have been largely eliminated for administration to infants under six months of age in the developed world, with the exception of influenza and diphtheria-tetanus vaccines in the United States and the routinely recommended diphtheria-tetanus-pertussis vaccine in the United Kingdom (Downey et al., 2010).

Clinical manifestations of mercury toxicity vary greatly depending on numerous factors, including: the amount of exposure (dose relative to body weight); dosing patterns (intermittent bolus, chronic, and acute); mercury species (ethyl, methyl, dimethyl, metallic, mercuric, and mercurous); route of administration (cross-placental, ingested, injected, inhaled, mucosal, and transdermal); excretion context (in utero, with antibiotics, immature commensal flora or bile production, and milk diets); and age and developmental context at the time of exposure (prenatal, postnatal, infant, toddler, child, and adult) (Blaxill et al., 2003).

Age of exposure is critically important for the autism-mercury hypothesis, since the proposed mechanism of mercury toxicity is specifically related to the developmental timing and consequences of exposure (Blaxill et al., 2003). Only two well-documented mercury exposure patterns fall close to the developmental window proposed in the autism-mercury hypothesis: congenital Minamata disease (CMD) and Pink disease, also known as acrodynia. CMD results from fetal exposure via cross-placental transfer of relatively high doses of methyl mercury ingested by the mother through contaminated fish. Acrodynia results from direct transdermal and mucosal exposures in infants and small children — often via teething powders — to inorganic mercury, specifically mercurous chloride in calomel (Nelson & Bauman, 2003). The typical manifestations following known mercury exposures in CMD and acrodynia bear little resemblance to the vague manifestations of mercurism described by Nelson and Bauman.

Emerging evidence supports elevated mercury exposure and unusual mercury metabolism in autistic children. An unpublished study observed young children with higher levels of exposure to thimerosal-containing vaccines and compared findings with a published study using the Vaccine Adverse Events Reporting System (VAERS) database (Downey et al., 2010). The Vaccine Safety Datalink (VSD) study found a relative risk of autism of 2.48 in infants receiving 62.5 micrograms or more of ethyl mercury by three months of age. This also correlates with increased prenatal mercury exposure in autistic children, resulting from both higher numbers of maternal amalgam fillings and a higher probability of receiving thimerosal-containing Rho D immunoglobulin injections (Gerber & Offit, 2010). Any such prenatal mercury exposures occur against a background of elevated mercury blood levels in women of childbearing age, with over 8% of women in one study showing blood mercury readings in excess of EPA-allowable levels. Lower levels of mercury have also been found in the first baby haircuts of autistic children compared to controls, suggesting reduced excretion rates, since the autistic group had elevated mercury exposures relative to controls. High levels of mercury have been detected in the urine of autistic children following chelation therapy with DMSA (Al Anbar et al., 2010).

Conclusion

Clinicians treating autistic patients have reported elevated mercury levels in urine following challenge with standard heavy metal chelators, and improvement in function after mercury removal via chelation. In one case study, the only known mercury exposure was from vaccines. These preliminary reports suggest that mercury may persist in tissue in some autistic individuals and may contribute to autistic symptoms. These findings support the hypothesis that mercury in vaccines may be a factor in the pathogenesis of autism (Downey et al., 2010).

Understanding the underlying biological mechanisms of thimerosal toxicity in populations genetically susceptible to mercury's effects might lead to effective medical treatments for autistic individuals. A positive finding of a thimerosal role would also provide added impetus for the removal of this non-essential compound from health and medical products in which it can still be found. These products include many pediatric vaccines used in developing nations, all US influenza vaccines, all mono- and divalent diphtheria and tetanus vaccines, some immunoglobulins routinely given to pregnant Rh-negative women, and some over-the-counter ear drops and nasal sprays.

The incidence of autism has increased tenfold in a decade (Schechter & Grether, 2008). Increases of this magnitude must have environmental roots. Increased mercury exposure is both biologically and epidemiologically plausible as a sole or contributing causal factor. If thimerosal truly had nothing to do with autism or any other neurodevelopmental disorder, all related studies would have reached the same conclusion: that it had no effect — positive or negative — on any outcomes, anywhere, at any time. All health outcomes would have been neutral. Instead, the body of research tells us that thimerosal's effects are both beneficial and harmful, neurologically protective and degenerative — suggesting that we truly know very little about its consequences at low-dose exposures.