Young-Geier Autism Study: What the—? (Part 1)

Like Orac, I'm perfectly happy to let EpiWonk (who appears far more qualified than I am) to dissect the methods of the recently published study by Heather Young and Mark and David Geier, which links thimerosal exposure to autism. However, given that the study is published in the Journal of the Neurological Sciences, I should be able to understand and critique it. I am, after all, a member of the journal's intended readership.

So here goes—although, like EpiWonk, I'm posting in installments, beginning with the article's introduction.

Thimerosal is an organic mercury-containing compound that is 49.55% mercury (Hg) by weight, and initially metabolized to ethylmercury compounds and thiosalicylate [3].

The mercury in thimerosal, a bacteriocidal vaccine preservation, exists in the form of ethylmercury that is bound to thiosalicylate. In an excellent historical review, Duke epidemiologist Jeffrey Baker, writes, "Much in the thimerosal debate hinges on the alleged similarity, or dissimilarity, of ethylmercury to methylmercury," and "[T]he chemical distinction is not trivial; it may be compared with that between ethanol (in the form of alcohol in wine) and its highly lethal counterpart methanol." The FDA concurs that ethylmercury should be distinguished from methylmercury.

In a 2002 statement, WHO wrote that the half-lives of methylmercury and ethylmercury are 1.5 months and less than 1 week, respectively, and concluded, "Thus, exposure to ethyl mercury in blood is relatively brief. Ethyl mercury is actively excreted via the gut, whereas methyl mercury accumulates in the body." These conclusions were reiterated by WHO in a 2006 statement.

The American Academy of Pediatrics and the US Public Health Service in 1999 [4] published a joint statement that urged "all government agencies to work rapidly toward reducing children's exposure to mercury from all sources." The statement recommended that Thimerosal be removed from vaccines as soon as possible as part of this overall process.

While the above statements by Young et al are true, the joint statement also reads: "[T]here are no data or evidence of any harm caused by the level of exposure that some children may have encountered in following the existing immunization schedule. Infants and children who have received thimerosal-containing vaccines do not need to be tested for mercury exposure," and, "The large risks of not vaccinating children far outweigh the unknown and probably much smaller risk, if any, of cumulative exposure to thimerosal-containing vaccines over the first 6 months of life."

Exposures to Thimerosal through pediatric vaccines, however, still occur in the US and worldwide. Thimerosal continues to remain in most formulations of influenza vaccine recommended for administration to pregnant women and infants in the US, and in many of the childhood vaccines used in other countries where multiple-dose vaccine vials are utilized [6].

In the United States, thimerosal has not been used as a preservative in routinely recommended childhood vaccines since 2001, with the exception of some influenza vaccines (containing ~25 μg of ethylmercury per 0.5-mL dose); these vaccines are also available in thimerosal-free formulations. Young et al cite a 2002 statement from WHO, which concluded in 2006 that findings from 4 independently conducted epidemiological studies in the United Kingdom, Northern Ireland, and Denmark "do not challenge the safety of existing thiomersal-containing vaccines in infants."

WHO added, "Recently two studies were published alleging reduction of neurodevelopmental disorders in the United States of America following discontinuation of thiomersal-containing vaccines in the national immunization programme. The Committee found the conclusions made by the authors unconvincing due to the study design, and the data source...The Committee concluded, and advises accordingly, that there is no reason on grounds of safety to change current immunization practices with thiomersal-containing vaccines, as the risks are unproven."

The authors of at least one of the studies dismissed by WHO are (you guessed it) Mark and David Geier. The other study dismissed by WHO is presumed to be a 2006 Geier study published in the same dubious journal, the Journal of American Physicians and Surgeons (which is not included in the PubMed database).

Hg exposure from Thimerosal-containing vaccines administered to American infants in the 1990s, in conjunction with environmental Hg exposure, resulted in some infants receiving cumulative Hg doses for the first 6 to 12 months of life that were in excess of the US [EPA], the US [FDA], and the US Agency for Toxic Substances and Disease Registry (ATSDR) safety guidelines established for methylmercury, a closely related chemical compound to the ethylmercury found in Thimerosal [7].

This statement deserves further explanation, and Baker provides important context. In response to a rider to the FDA Modernization Act, which was concerned with environmental mercury exposure, the FDA's CBER performed a risk assessment of thimerosal in vaccines. The study was completed in 1999, and as Baker writes, "The actual cumulative exposure varied considerably, given that not all manufacturers used the preservative." He continues, "[B]ut the CBER scientists calculated that a minority of infants could receive as much as 187.5 [μg] of ethylmercury during the first 6 months of life. Lacking any standard for ethylmercury, the CBER team compared this exposure to standards for methylmercury and discovered that it exceeded that set by the [EPA]."

For their support, Young et al cite, curiously enough, a 2005 Canadian reference that concludes, "The guidelines for long-term mercury exposure should not be used for evaluating risk from intermittent single day exposures, such as immunisation using thiomersal-containing vaccines...Because of the contribution to overall mercury exposure from breast milk and diet in later life, the removal of thiomersal from vaccines would produce no more than a 50% reduction of mercury exposure in infancy and <1% reduction over a lifetime." The Canadian authors did not advocate the use of thimerosal-free vaccines over current thimerosal-containing vaccines, particularly in developing countries.

It is important to note that the National Research Council of the US National Academy of Science in 2000 determined that there is a causal relationship between childhood methylmercury exposure and neurodevelopmental disorders [8].

This report concerned itself exclusively with methylmercury (the major source of which for Americans is contaminated fish) and found epidemiologic associations between high and/or chronic, environmental methylmercury exposure and developmental neurotoxic effects—nothing particularly new. There is scant mention of ethylmercury, and the Council makes no conclusions regarding any relationship between ethylmercury exposure and neurodevelopmental disorders (at least, not that I could find). 

Parenthetically the report did cite (among many references) a 1979 case report (Table 5-7) from Romania, in which a mother and her 3 children suffered neurologic, muscular, and cardiologic effects after consuming the meat of a sick hog that had eaten ethylmercury-tainted seed. Two of the children died, presumably due to cardiac arrest. Mercury poisoning was confirmed by very high levels in blood, hair, and 24-hour urine samples. This study was questionably cited in a 2007 review article by Geier, Sykes, and Geier to support their claim that "further incidents of mercury poisonings by ethylmercury compounds continued to offer substantial evidence and disclose a pattern of extreme toxicity produced by ethylmercury in humans."

Geier et al's brief discussion of the Romanian case report is accompanied by citations of the accidential ingestion of fungicide-tainted food in China (1984) and Ghana (1974). According to the EPA, methyl- and ethylmercury were used in fungicides for crop seeds up until the 1970s, but their use was banned in the United States and is "subject to severe regulatory restriction worldwide." In the Romanian case studies, the implicated fungicides contained 1%-2.5% ethylmercury, in which case 100 g (~3.5 oz) of fungicide would contain up to 2.5 g of ethylmercury (100,000 times more ethylmercury than that delivered in a dose of influenza vaccine).

Moreover, the examination of the vaccine data (with the exclusion of the questionable studies by Geier and Geier) doesn't support the generalization. In fact, the authoritative sources cited by Young et al in their introduction (specifically WHO and the AAP/US Public Health Service) conclude that there is no evidence of harm from thimerosal-containing vaccines. It is particularly curious that Young et al cite a 2002 statement from WHO, which specifically dismissed a study from Geier and Geier in 2006, calling the authors' conclusions "unconvincing."

Coming up: "Materials and methods," with probably heavy deferrals to EpiWonk.

HT to neurodiversity for providing EpiWonk link.

Image: iStockPhoto