The first of (I hope) many very bad days for antivaccinationists in 2009

ResearchBlogging.orgIt looks like I’ve been sucked into another streak again.

Regular readers know that examining the claims of the antivaccine movement with skepticism, science, and critical thinking has been a theme of this blog from the very beginning. If there’s one thing I’ve learned over the last four years, it’s that vaccine news seems to come in streaks. Often weeks will pass without much, and, because the antivaccine wingnuttery over at, for example, The Huffington Post and Age of Autism is such a constant that it blurs into background noise, provoking my attention only when someone really brings the crazy home in a way that produces a level of burning stupid that results in sufficient pain to my harried neurons that it finally provokes a response.

Oddly enough, the story I wrote about yesterday has yet to provoke a response. It couldn’t possibly be because it was a story of how not vaccinating leads to death from Hib infection, could it? Perish the thought! Maybe our boys (and girls) are slipping. Maybe, in spite of having the entire weekend to think of an angle to use to attack this story as not being evidence of the dangers of not vaccinating (given most of the children involved were completely unvaccinated, including the one who died). I’m wondering if that’s the same reason they haven’t come out of the woodwork yet to attack a study that was released on Monday.

It’s yet another nail in the coffin of the idea that thimerosal causes autism. You know, that hypothesis has so many nails holding its coffin shut that high explosives wouldn’t dislodge the door, but I can still hear pounding from inside the coffin. It’s pseudoscience trying to get out. It’s a good thing we have a stake like this to drive into its heart:

CHICAGO | A new study from Italy adds to a mountain of evidence that a mercury-based preservative once used in many vaccines doesn’t hurt children, offering more reassurance to parents.

In the early 1990s, thousands of healthy Italian babies in a study of whooping cough vaccines got two different amounts of the preservative thimerosal from all their routine shots.

Ten years later, 1,403 of those children took a battery of brain-function tests. Researchers found small differences in only two of 24 measurements and those “might be attributable to chance,” they wrote in the February issue of the journal Pediatrics, which was to be released Monday.

Only one case of autism was found, and that was in the group that got the lower level of thimerosal.

“Mountains of evidence”? I love it. Even journalists are starting to get it. The thimerosal hypothesis of autism is dead, dead, dead! This hypothesis is no more! It has ceased to be! It’s expired and gone to meet its maker! It’s a stiff! Bereft of life, it rests in peace! If the mercury militia wouldn’t keep nailing it to the perch it’d be pushing up the daisies! Its metabolic processes are now history! It’s off the twig! It’s kicked the bucket, it’s shuffled off this mortal coil, run down the curtain and joined the bleedin’ choir invisibile!! The thimerosal/mercury/autism hypothesis IS AN EX-HYPOTHESIS!!

Sorry, I got carried away. (Either that, or I’m channeling John Cleese.)

A news story is all well and good to read about the study, but it’s so much better, so much more satisfying, to go to the source and dig out the actual study by Tozzi et al, which is hot off the presses in the February issue of Pediatrics and entitled Neuropsychological Performance 10 Years After Immunization in Infancy With Thimerosal-Containing Vaccines. The study was done in Italy, and one of its great advantages is that the amount of thimerosal to which the infants were exposed was actually known, unlike many epidemiological studies, where sometimes the dose of thimerosal (and therefore mercury) had to be inferred from the vaccine schedule at the time.

The reason is that the children studied were children who had taken part in a randomized study of two different diptheria-tetanus-acellular-pertuss (DTaP) vaccines, one that contained thimerosal and one that did not:

In 1992-1993, 15,601 healthy, 2-month-old infants were enrolled in the Italian Trial on Pertussis Vaccines. 18-20 In this trial, infants were selected from the general population in 4 of Italy’s 20 regions (Fig 1) and were assigned randomly to receive, under double-blind conditions, 3 doses of 1 of 4 vaccines, 2 of which were DTaP vaccines from 2 different manufacturers. One DTaP vaccine contained 50 μ g of thimerosal (or 25 μ g of ethylmercury) per dose, and the other was thimerosal-free (2-phenoxyethanol was used as preservative). The 3 doses of DTaP vaccine were administered at 2, 4, and 6 months of age. To comply with Italy’s vaccination schedule, all children also received 3 doses of hepatitis B virus vaccine (child formulation), each of which contained 25 μ g of thimerosal (or 12.5 μg of ethylmercury), at 2, 4, and 12 months of age, and a fourth dose of diphtheriatetanus vaccine, which contained 50 μg of thimerosal (or 25 g of ethylmercury), at 11 months of age…Therefore, in the first 12 months of life, the cumulative intake of ethylmercury, the mercury metabolite of thimerosal, was 137.5 μg for the children who were assigned randomly to receive the DTaP vaccine that contained thimerosal (“higher intake group”) and 62.5 μ g for those who received the thimerosal- free DTaP vaccine (“lower intake group”).

Ten years later, the children from this study living in the Veneto Region were studied. 1,403 children (697 belonging to the high thimerosal group and 706 belonging to the low thimerosal group) were recruited and subjected to a battery of eleven neurodevelopmental tests that produced a total of 24 neuropsychological outcomes to assess their development. The results were unsurprising and very much like the results of a study of thimerosal-containing vaccines as a risk factor for neurodevelopmental disorders other than autism that was published a year and a half ago. Most outcome measures showed no difference between the low and high thimerosal group, and the ones that did were small and entirely compatible with random chance due to multiple comparisons.

Oddly enough, the investigators did not control for multiple comparisons in their statistical analysis. I have no idea why they didn’t (they didn’t really explain), but they didn’t. They did, however, point out that for 78 different univariate statistical tests between all the outcome measures of all the tests (some outcome measures were tested by more than one test, and separate tests were done for males, females, and the entire sample), by random chance alone they would expect four “statistically significant” associations by univariate analysis. They found two. Girls had slightly lower scores in a measure of motor function, the finger-tapping test with the dominant hand, and a language test, the Boston naming test. As the authors described it, the differences were very small and of doubtful clinical relevance. My guess is that these apparent associations would probably disappear if a correction for multiple comparisons were applied. Moreover, only one case of autism was found, and that was in the group with the lower thimerosal dose.

I know what antivaccine activists will probably say when and if they get around to attacking this study. They will point out that there was not a group receiving no thimerosal. True enough. The authors themselves make that point. However, if thimerosal in vaccines were associated with autism, one would not expect that it would be different than any other toxin associated with an abnormality or condition. One would expect that the chance of autism or neurodevelopmental disorders would increase with increasing dose. The second argument that antivaccine advocates will likely try to make is that the dose-response curve has a plateau, and that plateau is below 62.5 μg, hence the lack of difference between the two groups. There’s just one problem with that argument. An exposure to 62.5 μg, to which the low exposure group was exposed, corresponds to roughly the total amount of mercury in thimerosal to which American infants were exposed in 1989–before the alleged “autism epidemic.” Even if mercury caused autism and there was a plateau in the dose-response below a dose of 62.5 μg, that would not be consistent with the antivaxers’ other pet claim, that an autism epidemic started in the 1990s because of the increasing amount of thimerosal exposure due to vaccines. That couldn’t have happened if a dose of thimerosal less than 62.5 μg maxed out the risk of autism, because 62.5 μg below the baseline exposure before the alleged “autism epidemic” started. The two claims (that of an autism epidemic in the 1990s due to increasing amounts of thimerosal in vaccines versus that of an effect that maxes out before a 62.5 μg cumulative dose of mercury from thimerosal) are mutually contradictory. I suppose antivaccinationists could postulate a threshold effect that doesn’t occur until a dose above 137.5 μg. Unfortunately for them, then they would have the problem of how long they ranted that any mercury was toxic and any mercury was unacceptable, not to mention the–shall we say?–inconvenient epidemiological evidence that autism rates did not plummet back to 1980s levels after 2001, which was when thimerosal was removed from most childhood vaccines and mercury exposure from vaccines plummeted to well under 62.5 μg.

Not that science, logic, or reason ever penetrate the brains of antivaccinationists. For example, let’s take a look at what they are saying in that bastion of only the craziest antivaccine looniness, a belief utterly resistant to change. That’s right, I’m talking about the Mothering.com forums, where anyone who criticizes antivaccine rhetoric or comes out as pro-vaccine risks being banned from the forums. Let’s see what they’re saying there. A selection of comments, with a little not-so-Respectful Insolence in parentheses afterward:

  1. “So basically this tells us kids who get some thimerosal are the same as kids who get more. And, despite our favorite doctor (ahem) gloating that it proves mercury is safe, it doesn’t.” (Straw man argument; what this shows is that there is no detectable dose-response curve from the two amounts of thimerosal. However, taken together with previous studies, it does strongly suggest that there is no correlation between thimerosal exposure and adverse developmental outcomes.)
  2. “It’s not just thimerosal a lot of people are worried about.” (Oh, no, the “toxin gambit“)
  3. “Don’t these kinds of studies just make you crazy? How can you say that it isn’t the mercury when you only compared more mercury to less mercury?” (The only reason these studies “make you crazy” is because they do not support your irrational belief, against all scientific evidence, that mercury causes autism.)
  4. “Because vaccine safety studies aren’t held to the same scientific standards as we have every right to expect. No true placebo/unvaccinated controls are ever done, nor long-term safety studies. And we have no idea what could potentially happen when we combine so many vaccines the way they do.” (Placebo/unvaccinated controls would be utterly unethical, for reasons explained to these morons again and again and again and again. It never sinks in.)
  5. “ugh. another useless study.” (It’s only “useless” because it doesn’t show what you want it to show.)

And, most hilarious of all, in response to a question, “I would like to know why people are afraid of DNA. References supporting your DNA fears, anyone? There is DNA in hamburgers, sushi, chicken, any meat you eat. What’s the big deal?”:

There is a huge difference between eating something in it’s natural state, and having bits and pieces selected by scientist injected into your blood stream while floating in a bunch of toxic chemical.

But that’s not the most burning stupid. I know, I know, it’s hard to believe that anything could be dumber than the statement above. After all, vaccines are not injected directly into the bloodstream, and the chemicals in vaccines are not toxic at the doses given. (The concept of “the dose makes the poison” appears to elude these Einsteins.) In general, DNA is chemically the same whether it is in its “natural state” or genetically engineered. All that differs is the sequence of base pairs. In any event, after reading that post, I thought that the scientific ignorance on display in the Mothering.com forums couldn’t get any worse. I was wrong. Boy, oh, boy was I wrong! This is the worst:

One form of DNA is handled naturally by the gastrointestinal system, which is designed by millions of years of evolution to properly deal with the oral ingestion of animal tissue, and the other form of DNA is tinkered with in a lab, mixed in a disgusting cocktail of toxic substances, and then directly injected into the body, bypassing the body’s basic defenses, where it does who-knows-what to the immune system and wreaks havoc on the body, possibly forever.

Yeah, they’re totally the same.

The stupidity waves emanating from the quote above could probably bend space-time into an endless loop of stupid, trapping all sentient life within it. I mean, my brain almost exploded under the onslaught of such horrific idiocy. I sincerely apologize to those of you with a science background–especially those of you with a biology background, or, even more so, to those of you with a background in molecular biology or evolutionary biology. I realize that reading that quote must have caused you intense pain, your every neuron crying out for release. Perhaps you even experienced a wave of neuronal apoptosis from the waves of dumb. I’m sorry, but you just had to see it to believe it.

Unfortunately, no matter how much scientific evidence exonerates the mercury in thimerosal in vaccines as a cause of autism, there will be the lunatic fringe that absolutely, positively refuses to believe it. They just know that mercury causes autism. The smarter antivaccine zealots have started to realize that science is coming down definitively against the thimerosal hypothesis. Heck, even the more obtuse ones, like J.B. Handley, have started to back away from their former mantra of “it’s the mercury, stupid.” The unrelenting mountain of evidence (I really like that term) failing to confirm the thimerosal hypothesis is the very reason why antivaccinationists have started to shift away from it, choosing to focus on vaccines themselves instead of any single ingredient, moving to vague claims that are difficult to falsify experimentally or epidemiologically. They realize they’ve made a serious tactical error by lashing themselves to a falsifiable hypothesis because the hypothesis has been falsified. Even though the amount of mercury in the vaccines infants receive has fallen to levels well below what infants used to receive in the 1980s, autism rates have not fallen, as would be predicted by the thimerosal hypothesis. You don’t often see epidemiological evidence more slam-dunk than that. That’s also why antivaccinationists have changed their story to “too many too soon” and coined the brilliantly Orwellian “Green Our Vaccines” slogan.

Science is ready to move on. The thimerosal hypothesis has been about as definitively falsified as is possible for a hypothesis involving a large population. Unfortunately, antivaccine zealots will not let science move on. Truly, the thimerosal hypothesis is the zombie that will not die.

Oh, well, at least Monday was a bad day for antivaccinationists, the first of what I hope will be many in 2009.

REFERENCES:

A. E. Tozzi, P. Bisiacchi, V. Tarantino, B. De Mei, L. D’Elia, F. Chiarotti, S. Salmaso (2009). Neuropsychological Performance 10 Years After Immunization in Infancy With Thimerosal-Containing Vaccines PEDIATRICS, 123 (2), 475-482 DOI: 10.1542/peds.2008-0795