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At least Eli Stone was good for one thing

ResearchBlogging.orgI did not watch Eli Stone last Thursday.

I didn’t really need to, given that prerelease descriptions made it clear that the show’s pilot episode was nothing more than a load of antivaccination propaganda. Indeed, it was so bad that the American Academy of Pediatrics actually took the step of drafting a public letter to ABC asking it either to can the show or run a disclaimer stating that science does not support the contention in Eli Stone that mercury in vaccines is a major cause of autism. In response, David Kirby, the Energizer Bunny of the mercury militia, posted a predictable screed accusing the AAP of trying to “censor” ABC, a truly hilarious proposition, given that ABC and its parent company Disney probably spend more in a day than the entire yearly budget of the AAP–and it has the airwaves as well. Equally predictably the “luminaries” of the mercury militia lapped it up, gloating that ABC’s running the show was some sort of victory.

In other words, things played out pretty much as I expected them to.

From perusing a copy of the show’s script that was sent to me, I can see that perhaps the worst thing about Eli Stone is not the antivaccinationist crap in its pilot. It’s rather that Stone, who starts out in the stereotypical way as a greedy bastard who defends large corporations for huge sums of money but then has a revelation that leads him to become some sort of modern day “prophet” who is fighting against his former corporate masters for the little guy. What appears to be an overarching theme of the show is an argument for faith over reason. Indeed, that seems to be the crux of Stone’s argument against the vaccine manufacturer he is suing for having caused his client’s autism. In the pilot, “faith” that thimerosal in vaccines causes autism won out over the science that shows that it does not to the tune of a $5.2 million award to the autistic child. Lovely message. Perhaps murderers nailed by forensic CSI-style science could start using that argument: “Your honor, I know that science shows me to be guilty as sin, but you can never really know for sure. Have faith that I didn’t do it.” Yeah, that’d fly real well.

One consequence of Eli Stone that I didn’t even come close to foreseeing was that the AAP decided to release early a study that demonstrates the ethyl mercury in thimerosal used in vaccines is excreted far more rapidly than methyl mercury, the organic form of mercury that is most commonly used as a standard (mainly because far more about its pharmacokinetics in humans is known). According to the press release:

New research from the University of Rochester suggests that infants’ bodies expel the thimerosal mercury much faster than once thought – thereby leaving little chance for a progressive building up of the toxic metal. This debunks the myth, believed by some parents and some pediatricians, that the gauntlet of thimerosal-containing shots many infants received in the 1990s – when the average number of vaccines kids received increased sharply – had put them at risk for developmental disorders.

“Thimerosal has been used for decades, but the surge in vaccinations caused fear that possible accumulations of ethyl mercury, the kind in thimerosal, might exceed safe levels – at least, when based on the stringent risk guidelines applied to its better-understood chemical cousin, methyl mercury, which is associated with eating fish,” said Michael Pichichero, M.D., professor of Microbiology/Immunology, Pediatrics and Medicine at the University of Rochester and the study’s main author.

But scientists are learning that the two mercury species actually behave quite differently. In fact, the body rids the kind found in thimerosal more that 10 times faster than it removes the kind one might encounter in a Friday night fish fry.

Now, on to the study itself. The reason I didn’t blog about this last week, when the press release was made, is that I didn’t have access to the study itself until this weekend, and I always like to read the study itself whenever possible before blogging about it. First, here’s a little background. There are two primary forms of organic mercury that people absorb. There’s methyl mercury, which is the sort that is most commonly absorbed from the diet, and there’s ethyl mercury, which is the form found in thimerosal. An ethyl group has one extra carbon in its hydrocarbon, with two carbon units rather than the one that is found in methyl mercury. But is this relatively small difference enough to affect how the two are handled by the body? Until fairly recently, scientists tended to extrapolate from data on methyl mercury when discussing ethyl mercury, but this study by Michael E. Pichichero, MD of the University of Rochester, entitled Mercury Levels in Newborns and Infants After Receipt of Thimerosal-Containing Vaccines, looked specifically at ethyl mercury levels in a large number of infants.

This study was a followup study to an older pilot study published in 2002 in the Lancet in which thimerosal elimination was studied in 40 infants. Pichichero et al found that thimerosal-containing vaccines (TCVs) did not elevate mercury levels in the blood above levels considered safe and that mercury was rapidly eliminated from the stools. This new study expands on these observations by increasing the number of infants to 216 and looking at three different ages: Newborns (Group 1), 2 month olds (Group 2), and 6 month olds (Group 3). Each cohort received the vaccinations recommended for its age. Because thimerosal is no longer used in most childhood vaccines in the U.S. and Europe, the study was done in Argentina, with blood samples taken before standard, routine recommended vaccination and then at different time points after vaccination. In order to minimize the number of needlesticks, babies only had one blood draw after vaccination, done at different times for different infants. The results were then pooled, and a one compartment first order pharmacokinetics model was applied to the pooled data, taking into account age and weight. In addition, urine and stool samples were also analyzed for mercury, although there were a few children who were unable to contribute an adequate blood sample for mercury determination. Both methyl and ethyl mercury were measured, as was inorganic mercury, to try to differentiate sources whenever possible.

The findings of the study can be summarized as follows:

  1. Mercury was measured in the vaccines themselves, and the mercury detected was consistent with the amount stated by the manufacturers and that the mercury in vaccines was exclusively ethyl mercury.
  2. The highest levels of mercury in blood were detected in the first samples obtained after vaccination (ie, at 12 hours after vaccination in the newborn group and at 24 hours after vaccination in the 2- and 6-month-old groups).
  3. Regardless of age group, mercury levels were relatively low, with the highest level detected being 8.0 ng/mL in a newborn 12 hours after receiving the birth dose of HBV vaccine that contained 32.5 μg of mercury, suggesting a low risk for any sort of mercury-related toxicity, particularly taking into account how rapidly the mercury is eliminated.
  4. The halflife of mercury in the blood after administration of TCVs ranged from 2.0 days (2 month olds) to 3.7 days (newborns).
  5. Mercury was detected in virtually all stool samples tested and increased significantly after vaccination in all 3 groups. Mercury was detected in stools throughout all the sampling time points and fell slowlly towards normal. This pattern is consistent with the liver eliminating the mercury. However, how much of the mercury was eliminated this way could not be precisely calculated because 24 hour collections were not done.
  6. Mercury was nearly undetectable in urine in all samples. Because mercury can be toxic to the kidneys, a blood marker for kidney damage was also measured. It was not elevated, indicating no damage.

The bottom line is that the elimination of ethyl mercury is much faster than that of methyl mercury ingested orally (a half life of 2-4 days compared with a half life of 44 days, respectively). At the very least this observation means that basing toxicity estimates for thimerosal in vaccines on toxicity estimates based on the body’s elimination of methyl mercury is scientifically inappropriate. It also suggests that it is highly unlikely that mercury from vaccines accumulates to cause any sort of toxicity, much less autism (the symptoms of which are not consistent with mercury toxicity anyway). It does not, as the authors point out, directly assess the toxicity of ethyl mercury, but it does provide highly useful information for estimating the risk based on standard dosages, at least in countries that still use TCVs. It is also consistent with a recent study in infant monkeys, which found a similar result and a lower distribution of mercury in the brain when compared with methyl mercury. As the press release states:

To illustrate, researchers cite that infants in the 6-month-old group – who, in their lifetimes, had encountered more total ethyl mercury that any other group studied – still had the same pre-vaccination blood-mercury levels before their checkups as most 2-month-olds had before theirs. This suggests that, before each round of shots, the mercury has plenty of time to be cleared.

Finally, there was a rather interesting side observation made. Some methyl mercury was detected in all of the samples, despite the fact that infants are not commonly fed fish or fish-based products in Argentina. The amount of methyl mercury ranged from 1% to 50% of the total organic mercury measured, which suggests that environmental exposure is likely to be a more significant source of long term mercury exposure than any vaccine regimen currently in use.

This study is yet another nail in the coffin of the “TCVs cause autism” claim made with such fanfare a few years ago by the mercury militia. It suggests that, not only do the epidemiological data fail to support any such link, but that even science as basic as pharmacokinetics fails to support a link.

Of course, antivaccinationists are not pleased with this study, both because it was released early to combat the lies on Eli Stone but also because it comes hot on the heels of the large California study that became the latest in the line of large epidemiological studies that failed to find a link between TCVs and autism. Indeed, antivaccinationist and prominent member of the mercury militia, Barbara Loe Fisher, swings and misses trying to cast doubt on the study:

Here is what all the fuss is about (for today at least): Pichichero claims his study of about 200 babies and children, who were injected with vaccines containing ethyl mercury (thimerosal), showed that measurable mercury levels in the blood of the children were gone within 3.7 days. This, says Pichichero, is much quicker than the average 44 days it takes for methyl mercury (found in fish) to be undetectable in the blood. Ergo, he says, exposure to thimerosal does not cause brain damage or autism!

A straw man argument. The study states explicitly that it does not say that, only that this pharmacokinetic information is useful in estimating risk, which, based on how fast mercury is eliminated, appears to be low. Worse, Fisher is too scientifically illiterate to know what a half life is. Here’s a clue, Barbara: A half life of 3.7 days does not mean that the mercury was gone in 3.7 days. It means that half of it was. Then, in another 3.7 days, half again was gone, leaving 25% of the original amount, and so on until mercury levels fall to the point where they are indistinguishable from zero. Geez, learn a bit of science or at least read the press release, whose author was kind enough to explain what a half life is! Having just demonstrated her scientific ignorance, Fisher continues:

Not so fast, says Thomas Burbacher, M.D., a scientist who studies the biological effects of ethyl mercury on primates. “Just because it came out of the blood doesn’t mean it is excreted from the body. It could have gone to the brain. In primates, you actually get more mercury in the brain after exposure to ethyl mercury than with methyl mercury – it has an easier time crossing the blood brain barrier.” HERE.

Another straw man. Although what Burbacher says is technically true, Fisher and Burbacher forget to notice that the Pichichero study did look at urine and stool and found a considerable amount of mercury in the stool, strongly suggesting that the stool is the primary means of elimination. True, the stool studies were not sufficiently rigorous to account for all of the mercury elimination. It was acknowledged in the study that it’s possible that a two-compartment pharmacokinetic model, in which the ethyl mercury enters the blood and then is taken up in tissues, has not been ruled out. However, while in the process of doing the definitive study that will answer the question of whether all the mercury is excreted in the feces, Pichichero, citing the monkey study that shows no significant accumulation in the brain, retorts:

“There is a direct relationship between the amount of mercury in the blood — and how long it stays in the blood — and the ability of mercury to get into the brain to produce developmental problems,” he says. “We did not prove there was not deposition of mercury in other parts of the body, but we prove that the half-life of ethyl mercury from thimerosal is low, excretion is high, and the kidneys — an organ very sensitive to the effects of mercury — were not damaged.”

Again, Fisher has no clue what she’s talking about and Burbacher is just pulling a rationalization out of his nether regions. The bottom line is that the hypothesis that mercury in TCVs causes autism somehow has been extensively investigated by both epidemiological studies, clinical studies, and basic science. It has been found not to be consistent with the evidence. Unfortunately, antivaccinationists like Barbara Loe Fisher can’t let go and just admit that they were wrong.

Pichichero, M.E., Gentile, A., Giglio, N., Umido, V., Clarkson, T., Cernichiari, E., Zareba, G., Gotelli, C., Gotelli, M., Yan, L., Treanor, J. (2008). Mercury Levels in Newborns and Infants After Receipt of Thimerosal-Containing Vaccines. PEDIATRICS, 121(2), e208-e214. DOI: 10.1542/peds.2006-3363

By Orac

Orac is the nom de blog of a humble surgeon/scientist who has an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his copious verbal meanderings, but just barely small enough to admit to himself that few probably will. That surgeon is otherwise known as David Gorski.

That this particular surgeon has chosen his nom de blog based on a rather cranky and arrogant computer shaped like a clear box of blinking lights that he originally encountered when he became a fan of a 35 year old British SF television show whose special effects were renowned for their BBC/Doctor Who-style low budget look, but whose stories nonetheless resulted in some of the best, most innovative science fiction ever televised, should tell you nearly all that you need to know about Orac. (That, and the length of the preceding sentence.)

DISCLAIMER:: The various written meanderings here are the opinions of Orac and Orac alone, written on his own time. They should never be construed as representing the opinions of any other person or entity, especially Orac's cancer center, department of surgery, medical school, or university. Also note that Orac is nonpartisan; he is more than willing to criticize the statements of anyone, regardless of of political leanings, if that anyone advocates pseudoscience or quackery. Finally, medical commentary is not to be construed in any way as medical advice.

To contact Orac: [email protected]

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