Tuesday, September 7, 2010

On anti-vaxers, science, and sticks of butter

It's a love-hate thing between the two, the anti-vax coven and science. Science has no feelings about it at all, while the anti-vaxers hate science unless, of course, they've found some "science" that they can take and twist and spin and contort until it fits into the mold that they've formed around their ability to think.

Right now, for the anti-vax crowd, they're really feelin' the luv for the sciency types. Check out Age of Autism and the latest spin on what they view as "support" for the mercury-autism link. No, I double-dog dare you. You can do it. Just get a bucket first.

The study that has them falling in luv all over again comes to us courtesy of the journal Neurochemistry Research. You can find the full-text paper here. (Edited to add: I also have found this conference PDF in which the senior author of this study, Maria Majewska, lays out her argument for pursuing the vaccine-autism connection. If you're wondering what their dog is in this hunt, you'll hear some barking here. It appears that the senior author on this study has a history that includes signing a petition in support of Andrew Wakefield and denying that H1N1 was a pandemic).

Naturally, I have a few points to make.

1. The entire hypothesis of the study relies on a set of papers that are suspect at best.
The authors state that, "Early life exposure to mercurials, including (thimerosal), is suspected to be a pathogenic factor in several neurodevelopmental disorders." I read that and thought to myself, "Really? What are the citations for that?" Well, here they are from the paper, citations 7 through 10; note the authors, journals, and type of publication, and draw your own conclusions:

Bernard S, Enayati A, Redwood L, Roger H, Binstock T (2001) Autism: a novel form of mercury poisoning. Med Hypotheses 56: 462–471


Mutter J, Naumann J, Schneider R, Walach H, Haley B (2005) Mercury and autism: accelerating evidence? Neuroendocrinol Lett 26:439–446

J Neurol Sci 271:110–118

In other words, the hypothesis, from a scientific viewpoint, is dead in the water. These citations offer little to prop it up. There goes any reason for doing the study.

2. The core of the study design is the claim that the authors are using relevant Hg/thimerosal exposures. The citation for the concentration used is...their own previous paper. Red flag.
The authors rely on what they aver are relevant doses of thimerosal, giving 12 mcg of Hg/kg as the exposure that would reflect what children receive "in some countries." I checked the citation they offered up to support that assertion. Guess what? It's one of their own papers. Reference 11--see for yourself. Self-citing for the core of your study design? Not a great idea.

3. The doses of thimerosal are claimed to be representative of real exposures. They are not.
The FDA has this to say about thimerosal in vaccines: "When thimerosal is used as a preservative in vaccines, it is present in concentrations up to 0.01%. A vaccine containing 0.1 thimerosal as a preservative contains 50 mcg of thimerosal per 0.5 ml dose, or approximately 25 mcg of mercury per 0.5 ml dose."

Look at this table. It shows the per 0.5 ml concentration of thimerosal in current vaccines. One thing you may note is how few vaccines contain or ever have contained thimerosal. As you can see, the injectable flu vaccine contains the highest concentration of actual Hg, at 25 mcg/0.5 ml. This vaccine is not used in children under age 6 months. The average 6-month old child is about 15 lbs (mine are bigger, so this is conservative for us). That's about 6.8 kg. A child receiving this flu shot right at age 6 months would thus receive about 3.7 mcg of Hg/kg. Got that? 3.7 mcg/kg.

In their study, the authors don't specifically use thimerosal concentrations but instead refer to the concentration of Hg in the thimerosal they use. The lowest concentration of Hg the authors used in their study, one they claim is relevant and applicable for "many countries," based on their self-cited reference, is 12 mcg/kg. In other words, that dose of Hg is 3.2 x what a 6-month old would receive in one of the few remaining shots that contains thimerosal or ever has contained it.

Their starting dose is at least 3.2 times the relevant exposure of Hg. But they're not finished. They don't use that dose once. They use it four times, injecting the newborn rats on days 7, 9, 11, and 15 of life, each time with 3.2 times the actual relevant exposure of Hg, for a total of 48 mcg of Hg/kg in a little over a week. Indeed, even if 12 mcg were the relevant exposure, they're dosing their animals with it four times within a week, give or take, giving us ~13 fold the relevant exposure.

Bottom line: Their alleged "relevant" lowest exposure dose is waaaay too much for a real-world model--by an order of magnitude.

4. They find no significant results with their lowest dose, the one that's supposed to be a real-life model and is not.
In fact, any significance they do find is with these enormous exposures, the highest of which adds up to a total of 12,000 mcg of Hg/kg over the week dosing period. Yes, that comes out to 12 mg of Hg for every kilogram of baby rat. For a 6-month old human baby weighing 15 pounds, that would be 8.16 g of mercury. In everyday terms, that's 0.02 pounds, or nice spoonful's worth of mercury, about the size of a pat of butter.

So, no surprise that with those higher doses, they got some results. Look at their tables, 1-3. You'll find that there is no report of that lowest, allegedly relevant dose having a significant effect. Only their huge doses had any effect.

5. They get away with saying this in the Discussion:
"The effect was clearly noticeable already at the lowest dose of thimerosal (12 mcg Hg/kg), equivalent to those used in pediatric vaccines, although at this dose it did not reach statistical significance."

Aaargh. They get away with saying this about a fairly subjective assessment involving cell/molecular staining, which can be notoriously difficult to quantify. No decent reviewer would have let this sentence get by. You're not "supposed" to bring up non-significant data unless there is some shadow of clinical application that might make it worth mentioning.

6. The Discussion itself is one long string of speculation.
Again, something a reviewer of decent stripe would have reined in.

7. They cite a Medical Veritas paper in the references:
Haley BE (2005) Mercury toxicity: genetic susceptibility and synergistic effects. Med Veritas 2:535–542

Geiers? Med Veritas? Self citation? The foundations of this work are shaky indeed, and the results? They tell us...hey, guess what...butter-pat-sized doses of mercury in young mammals can kinda affect some neurological stuff.

Not terribly useful in the end, is it? Doesn't autism deserve better? Without the spoonful of mercury?

NB: Math, schmath. Needed to move a decimal over and have. Doesn't change any of the critique, just my butter analogy.