Burbacher

1.  Introduction

Thomas Burbacher is an Associate Professor, Env. and Occ. Health Sciences at the University of Washington School of Public Health and Community Medicine. His research interests are listed as:

"Behavioral toxicology, developmental effects of pre- and postnatal exposure to environmental contaminants."

2.  Comparison of Blood and Brain Mercury Levels in Infant Monkeys Exposed to Methylmercury or Vaccines Containing Thimerosal

2.1  Abstract

Thimerosal is a preservative that has been used in manufacturing vaccines since the 1930s. Reports have indicated that infants can receive ethylmercury (in the form of thimerosal) at or above the U.S. Environmental Protection Agency guidelines for methylmercury exposure, depending on the exact vaccinations, schedule, and size of the infant. In this study we compared the systemic disposition and brain distribution of total and inorganic mercury in infant monkeys after thimerosal exposure with those exposed to MeHg. Monkeys were exposed to MeHg (via oral gavage) or vaccines containing thimerosal (via intramuscular injection) at birth and 1, 2, and 3 weeks of age. Total blood Hg levels were determined 2, 4, and 7 days after each exposure. Total and inorganic brain Hg levels were assessed 2, 4, 7, or 28 days after the last exposure. The initial and terminal half-life of Hg in blood after thimerosal exposure was 2.1 and 8.6 days, respectively, which are significantly shorter than the elimination half-life of Hg after MeHg exposure at 21.5 days. Brain concentrations of total Hg were significantly lower by approximately 3-fold for the thimerosal-exposed monkeys when compared with the MeHg infants, whereas the average brain-to-blood concentration ratio was slightly higher for the thimerosal-exposed monkeys (3.5 ± 0.5 vs. 2.5 ± 0.3). A higher percentage of the total Hg in the brain was in the form of inorganic Hg for the thimerosal-exposed monkeys (34% vs. 7%). The results indicate that MeHg is not a suitable reference for risk assessment from exposure to thimerosal-derived Hg. Knowledge of the toxicokinetics and developmental toxicity of thimerosal is needed to afford a meaningful assessment of the developmental effects of thimerosal-containing vaccines. [1]

2.2  The Issues

This study looked at the accuracy of using methylmercury exposure to measure ethylmercury exposure, which was the standard way of assessing the risk of ethylmercury (which thimerosal is) at the time. This paper was seen as a 'smoking gun' in the establishment of a link between thimerosal and autism because up until this point science had assumed meth and eth mercury cleared the body at the same rate. However, the papers reputation as a smoking gun establishing that thimerosal caused autism was overstated. Burbacher et al made the following comments:

"The second slower phase of washout could also represent the gradual biotransformation of ethylmercury (the presumed principal organic form of Hg after thimerosal administration) to Hg-containing metabolites that have a different tissue distribution or are more slowly eliminated. Further investigations of the disposition fate of thimerosal-derived mercury should address these issues."

In other words ethylmercury transforms to mercury containers that are more slowly eliminated than methylmercury. However, Burbacher et al are quick to note that they have not established that this is actually an issue or that it leads to any causal relationship to autism.

"The average brain-to blood partitioning ratio of total Hg in the thimerosal group was slightly higher than that in the MeHg group. Thus, the brain-to-blood mercury concentration ratio established for MeHg will underestimate the amount of mercury in the brain after exposure to thimerosal."

In other words, Burbacher et al conclude that levels of methylmercury cannot accurately represent levels of ethylmercury in the body.

"Data from the current study predicts that while little accumulation of Hg in the blood occurs over time with repeated vaccinations, accumulation of Hg in the brain of infants will occur. Thus, conclusion regarding the safety of thimerosl drawn from blood Hg clearance data in human infants receiving vaccines may not be valid, given the significantly slower halflife of Hg in the brain as observed in the infant macaques."

In other words, mercury from vaccines doesn't accumulate as much in blood as it does in the brain and thusly, using blood levels of mercury to represent brain levels of mercury is innacurate.

"The key findings of the current study are the differences in the disposition kinetics and demethylation rates of thimerosal and MeHg. Consequently, MeHg is not a suitable reference for risk assessment from exposure to thimerosal derived Hg. Knowledge of the biotransformation of thimerosal, the chemical identity of the Hg-containing species in the blood and brain, and the neurotoxic potential of intact thimerosal and its various biotransformation products, including ethylmercury are urgently needed to afford a meaningful interpretation of the potential developmental effects of immunization with thimerosal-containing vaccines in newborns and infants. This information is critical if we are to respond to public concerns regarding the safety of childhood immunizations."

In other words, Burbacher repeats his conclusions that blood vs brain is not valid and that methHG vs ethHG is not valid either. He then goes on to state that more research is needed into what the toxic effects of thimerosal might be.

2.3  The Talking Points

This paper was seen as 'the smoking gun' of the thimerosal/autism connection by many believers of the hypothesis. This was undoutably due to misunderstanding the papers conclusions. What Burbacher et al tried to establish was that methylmercury and ethylmercury were different and could not be used to illustrate each otehrs speed of elimination from the body. This paper in no sense attempted to make a causative connection between thimerosal and autism.

This paper is also presented as evidence of an association between thimerosal and neuroglial activation Vargas et al but the only mention of microglial and astroglial activation is actually a reference to another study with a much higher dose of MeHg. In fact Burbacher has observed microglial activation in primates after exposure to mercury salts which presents two possibilities in this study:

1. Neuroglial activation patterns were investigated and no changes were observed before the animals were sacrificed. This is the most common explanation which can be interpreted to mean there are no acute effects on CNS glial cells, inconsistent with reports of immediate regression following vaccination with TCV.

2. Neuroglial activation was not in the scope of this study.

A lot of people also drew the conclusion from Burbacher et al that ethylmercury (thimerosal) was actually less toxic than methylmercury.

Blogger Bartholomew Cubbins, a research scientist, had some comments to make on the methodology Burbacher et al used to measure mercury:

"The real problem with this paper is the fact that a direct measurement of each compound of interest is not accomplished. Rather, the tissue is homogenized and then an organic extraction is conducted. From the different phases come the parts of the sample that are applied to the spec.

The spec measures the concentration of the element mercury. It is up to the user to then attribute that concentration to the phase and thus, to the form of mercury that resided in the tissue.

So what happens to intact thimerosal during the organic extraction? Why didn't the group inject homogenate with thimerosal, ethyl, methyl, and inorganic mercury to provide a baseline by which extraction efficiency and extraction degradation could be measured and taken into account? I see assumptions bundled with missing data."

In other words, when the Burbacher team performed the extraction of mercury from the blood or brain matter, they failed to introduce controls to ensure that the thimerosal was not degraded in any way as a result of the extraction process. This means they had to basically assume from the resultant possibly contaminated material how much was attributable to methylmercury and how much to thimerosal (ethylmercury).

Bartholomew Cubbins shot a Quicktime movie to demonstrate his points.

A few other issues with materials and methods: Burbacher used thimerosal free vaccines and added pure thimerosal. It is difficult to know how this fresh preparation compares with vaccine formulas when thimerosal is part of the manufacturing process and may have suffered some degradation to inorganic Hg in the vials before administration.

3.  Also See

Thimerosal | Deth | Hornig