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1)
Clearly ours was an in vitro study designed to explore the molecular actions of neurodevelopmental toxins on methionine synthase, not an examination of the biodistribution of organomercurials. That said, the assertion that ‘ethylmercury is unlikely to enter the brain at concentrations likely to be harmful’ is wishful thinking and simply untrue. To the contrary, results presented at the recent ‘Immunization Safety Review: Vaccines and Autism’ at the Institutes of Medicine showed the brain-to-blood ratio in primates to be 5.1 for ethylmercury and 3.4 for methylmercury.1 The elimination half-life of ethylmercury was indeed shorter than that of methylmercury (18 vs 59 days for brain clearance). However, there is evidence that autistic children have a significantly impaired capacity to clear mercury,2 due to lower levels of cysteine and glutathione, which probably accounts, at least in part, for their increased risk.
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2)
SH-SY5Y human neuroblastoma cells are the most widely employed cultured human neuronal cell line, and they express a native population of D4 dopamine receptors, making them uniquely suitable for the study of neurodevelopmental toxins on D4 receptor-mediated phospholipid methylation. Others have previously described the ability of thimerosal to induce apoptosis in primary cultures of human cerebral cortical neurons.3 We agree that the effects of neurodevelopmental toxins will depend on the timing of exposure. Thimerosal exposure in the first two postnatal years occurs during a period of exceptionally active synaptogenesis accompanied by the assembly of neuronal networks that are guided by attention. Impaired methylation during this period could have profound and long-lasting consequences for cognitive function.
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3)
We have observed similar potent effects of PI3-kinase inhibition and thimerosal on methionine synthase activity in several other cell lines (eg SK-N-MC and CHO cells) and in Epstein–Barr virus-immortalized human lymphoblasts.
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4)
Indeed, several other epidemiological studies did not find an association between levels of thimerosal exposure and autism rate,4, 5 although in some cases questions have been raised about the study design and potential investigator bias.6 One study did find a significant association between the total level of thimerosal exposure at 3 and 7 months and language delay in one HMO population, but not another.5 The inherent limitations of epidemiological studies to identify mechanistic factors suggests that studies focused on autistic subjects may be more fruitful in revealing risk factors and/or triggering agents than broad population-based approaches.
Clearly ours was an in vitro study designed to explore the molecular actions of neurodevelopmental toxins on methionine synthase, not an examination of the biodistribution of organomercurials. That said, the assertion that ‘ethylmercury is unlikely to enter the brain at concentrations likely to be harmful’ is wishful thinking and simply untrue. To the contrary, results presented at the recent ‘Immunization Safety Review: Vaccines and Autism’ at the Institutes of Medicine showed the brain-to-blood ratio in primates to be 5.1 for ethylmercury and 3.4 for methylmercury.1 The elimination half-life of ethylmercury was indeed shorter than that of methylmercury (18 vs 59 days for brain clearance). However, there is evidence that autistic children have a significantly impaired capacity to clear mercury,2 due to lower levels of cysteine and glutathione, which probably accounts, at least in part, for their increased risk.
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