Dr. Hornig's Autistic Mice
The Autism Diva has already addressed the topic of autistic mice and Dr. Hornig in some detail in her delightful post, "Rain Mouse?", so I'll try not to cover the same ground. Instead, I would like to address some of the technical aspects of the study.
In a nutshell, Dr. Hornig and her colleagues gave intramuscular (i.m.) injections of either thimerosal or a placebo to newborn mice. The mice were from three different strains - one that was susceptible to autoimmune disorders (SJL/J) and two that were not (C57BL6/J and BALB/cJ).
In order to simulate the immunization schedule given to human infants (see where they're going with this?), they gave the injections on the 7th, 9th, 11th and 15th days of life. For reference, human infants receive their immunizations at ages 2 months, 4 months, 6 months and 12 months (one year). However, mouse infancy is much more accelerated than human infancy, requiring the injections to be spaced closer together in order to happen during the same developmental stages.
A plan of overdosage:
The timing of the injections is the first flaw that I would like to address. While it is true that this dosing schedule allows the thimerosal to be administered in the same neurodevelopmental stage as in human infants, it overlooks a big fact of biology.
The plasma half-life (time that it takes for the plasma concentration to decrease 50%) of methylmercury in humans is variously reported as being between 40 and 56 days. There are no published studies of the half-life of thimerosal in humans, but animal studies make it likely that it will be longer. The half-life of methylmercury in mice is much shorter - 158 hours.
So, a dose of mercury given to a human will be half gone in about 50 days and, in a mouse, 6 1/2 days. Let's look at what this means in the context of this study:
If an infant is given a mercury dose at time zero (0) that produces a blood mercury level of 1.0 (arbitrary units), that blood level will be down to 0.44 after 60 days. A second dose at 60 days (see where I'm headed?) will bring the blood level to 1.44. In another 60 days, the level will be down to 0.63 and another dose will bring it up to 1.63. After waiting 180 days (about three half-lives), the blood level is down to 0.13 and a fourth dose will raise it to 1.13.
Now let's look at it from the perspective of the mice in this study. If they receive a dose at time zero that produces a blood level of 1.0 (arbitrary units), after two days, the blood level will only be down to 0.81. Another dose raises the blood level to 1.81 and, after another two days, it is down to only 1.46. Another dose raises the blood level to 2.46, which is down to 1.61 when the final dose raises it to 2.61.
So, the human experiences a maximum blood level of 1.63 (arbitrary units) and the mouse - since it is being dosed at a smaller fraction of its half-life - sees a maximum blood level of 2.61. In short, the mouse gets to a blood level 60% higher than the human.
The case of the underweight child:
Now, this all assumes that the mouse and the infant are not growing - which is not true - and that the doses they are getting are equivalent on a microgram per kilogram body weight basis, which also is not true. The study dosed the mice on a per kilogram basis equivalent to what a human infant would have received had they received their vaccinations on schedule. However - and this is a curious thing - they used the 10th percentile (10% of children that age weigh less, 90% weigh more) body weights for children at ages 2, 4, 6 and 12 months.
I found myself wondering, "Why didn't they use the 50th percentile (50% weigh more than this weight, 50% weigh less - sort of an 'average weight')?" I have no answer - but I have an idea. By using the 10th percentile, they were able to give the baby mice an even bigger dose of mercury. Let's run the numbers, as they say on NPR:
Dosing is based on the child receiving 62.5 micrograms of thimerosal at 2,4 and 6 months and 50 micrograms at 12 months. Using the numbers for 10th percentile weights and 50th percentile weights, this works out to doses of:
10th - 4.4 kg - 14.2 ug/kg
50th - 5.3 kg - 11.8 ug/kg (17% less)
10th - 5.7 kg - 10.8 ug/kg
50th - 6.8 kg - 9.2 ug/kg (15% less)
10th - 6.8 kg - 9.2 ug/kg
50th - 7.9 kg - 7.9 ug/kg (14% less)
10th - 9.0 kg - 5.6 ug/kg
50th - 10.3 kg - 4.9 ug/kg (13% less)
So, by using the 10th percentile weights, the authors were able to give the mice about 15% more thimerosal. This goes nicely with the dosing schedule to significantly raise the dose the mice receive.
The show must go on!:
What Dr. Hornig didn't show in her article, but is showing to concerned parents of autistic children, is the video of her autistic mice. The study article adresses such prosaic behavioral changes as decreased spontaneous movement, decreased exploration and decreased streotypic behaviors, but the video (CAUTION: large file) she shows includes such titillating tidbits as one mouse grooming another to death and another mouse biting its own tail. These, she says, are evidence that these mice have become autistic....
Hold the phone! Grooming is a social activity mice engage in, and autistic people are supposed to be averse to social interactions! And although self-injurious behavior is seen in autism, there are other, better explanations that were overlooked.
In fact, I felt a strange hot flush come over me as I watched the video (maybe it was just a hot flash). I have seen exactly this type of behavior before - but not associated with mercury.
Many years ago, I was associated with a group studying treatments for chronic neuropathic pain. The model we used was a rat model in which we injured the sciatic nerve and let it heal. A number of the rats would develop what was assumed to be neuropathic pain - evidenced (so we thought) by biting and chewing on the affected hind limb. It was a grisly sight and, what was worse, it wasn't really neuropathic pain.
Another group discovered that anything that caused abnormal sensation would cause rats (and other animals) to bite and gnaw on the affected limb. What I saw in these mice was exactly what we saw in the partially denervated rats. And - oh, by the way - mercury causes parasthesias (numbness and tingling). Dr. Hornig has probably managed to make these mice so neurotoxic that they are experiencing parasthesias - a common sign of mercury poisoning.
And now, a word from our sponsors!:
These days, no discussion of mercury and autism is complete without a thorough exposition of who paid for the study and who might have a conflict of interest. So, you might ask, who paid for this study?
The UC Davis M.I.N.D. Institute
The Coalition for Safe Minds
To remind you, the Coalition for Safe Minds' mission statement is:
"Our mission is to end the health and personal devastations caused by the needless use of mercury in medicines. "
But I'm sure that didn't influence the outcome of the study.