Autism Street

This week, blogger Not Mercury is back to collaborate on another article.

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- By Not Mercury and Do’C

Last month, we co-wrote about an opinion piece by Michael Wagnitz. We were critical of assertions, and an apparently liberal interpretation of what conclusions can be drawn from the research he mentioned. Mr. Wagnitz was kind enough to drop by in the comments of that post and clarify his position, part of which, to many, might look a little less than scientific:

I do not believe thimerosal causes autism. I believe thimerosal causes neuroinflammatory disesase, gastrointestinal injury and autoimmune problems. My only connection to autism is that my daughter has been labeled as such so they can refuse paying for proper medical care and instead push dangerous anti-psychotic drugs on her. Autism, for 90% of cases, is nothing but a word used to cover-up the damage done by thimerosal to millions of kids.

Well, Mr. Wagnitz appears to have written again - this time, in an article featured in an online magazine, American Chronicle. He has added some references this time around, which is a good thing, but are the implications of his writing supported by the science? Let’s have a look.

Rates of autism spectrum disorders have been rising at an alarming rate according to the U.S. Department of Education, Office of Special Education, Data Analysis Services.

We’re not exactly sure where this information comes from, but communication about the U.S. Department of Education’s 2002 Report to Congress seems like one possibility. Let’s read a little more about that from “Three Reasons Not To Believe In An Autism Epidemic” (Gernsbacher et al., 2005).

 - “The purpose of the federal Individuals With Disabilities Education Act (IDEA), passed in 1991, is to ensure that all children with disabilities are provided a free, appropriate, public education including an individually designed program. Schools comply with the IDEA by reporting to the federal Department of Education an annual ‘‘child count’’ of the number of children with disabilities served. It is the data from these annual child counts that have been the most egregiously misused in arguments for an autism epidemic.”

 - “For example, in October 2003, the Autism Society of America sent its 20,000 members the following electronic message: “Figures from the most recent U. S. Department of Education’s 2002 Report to Congress on IDEA reveal that the number of students with autism [ages 6 to 21] in America’s schools jumped an alarming 1,354% in the eight-year period from the school year 1991-92 to 2000-01” (emphasis added). What the Autism Society failed to note is the following fact (available in the Report to Congress, immediately under the autism data entries): Prior to the 1991–1992 school year, there was no child count of students with autism; autism did not even exist as an IDEA reporting category. Moreover, in 1991–1992, use of the autism reporting category was optional (it was required only in subsequent years).”

Bold emphasis is ours.

Most of the new cases are regressive or late on-set autism.

Evidence Mr. Wagnitz?

The diagnostic criteria for autism spectrum disorders are based on behavioral symptoms rather than a specific medical cause. In addition to psychological symptoms, many parents and physicians report conditions indicating a compromised immune system and gastrointestinal problems. This review looks at the most recent clinical studies indicating the causative agent may be mercury and tries to put this complicated puzzle together.

Okay, let’s have a look then.

Autism is a term used to describe a condition which affects the immune, gastrointestinal and central nervous system.

Apparently Wagnitz forgot to write “I believe”, like he did in the comments of our last post. Wagnitz almost began to define it correctly in the preceding paragraph, but fell way short. Autism (used broadly to refer to all autism spectrum disorders), is a condition that is characterized at its core, by social impairment. Yes, there are other behavioral aspects and criteria that are part of an accurate autism spectrum disorder diagnosis, but just because some parents and physicians report what Wagnitz may believe are “conditions indicating a compromised immune system and gastrointestinal problems” does not mean that the definition of autism changes.

It has been shown that many of the physical and behavioral symptoms identified in children diagnosed with autism have been previously present in past cases of mercury poisoning (Bernard et al.2001).

Not exactly. This paper was thoroughly refuted in 2003 by Nelson and Bauman, which stated the following as part of the conclusion:

 - “Nonspecific symptoms such as anxiety, depression, and irrational fears may occur both in mercury poisoning and in children with autism, but overall the clinical picture of mercurism—from any known form, dose, duration, or age of exposure—does not mimic that of autism.”

Currently there is no known cause of autism identified in the medical literature,

Apparently this may not be true. While cause(s) for the vast majority may be unknown, there are several known and very likely causes of DSM-IV autism identified in the medical literature: fragile x syndrome, phenylketonuria (PKU), tuberous sclerosis, 15q duplications, CDFE among the Amish, are just a few.

but by sifting through the most recently published clinical studies, one could make a compelling case that the causative agent is inorganic mercury (IHg).

Compelling to those who do not examine the science critically, perhaps.

Analyses of first baby haircut samples have shown that autistic children retain seven times more mercury than neurologically typical controls (Holmes et al. 2003).

Holmes et al. does not show that autistic children retain more mercury than neurotypical controls at all. This single, never replicated, and potentially critically flawed study showed that a small group of autistic children had mercury in their hair seven times lower than the controls in that study. The authors then hypothesized:

 - “If reduced overall mercury elimination is related to hair elimination, then autistic infants will retain significantly higher levels of mercury in tissue, including the brain, than normal infants. In light of the biological plausibility of mercury’s role in neurodevelopmental disorders, our study provides further insight into one possible mechanism by which early mercury exposures could increase the risk of autism.”

Emphasis ours.

One big “if” and a “look” at a “hypothetical” “might”. This hypothesis is not supported by the data in this study, nor is there any research that indicates mercury level in the hair is in any way related to overall mercury elimination. Additionally, the autistic children in this study did not have hair levels of mercury any lower than those shown by much larger studies, while the controls had extraordinarily high levels compared to much larger studies.

Studies show that Macaca fascicularis primates that were dosed with chronic levels of methylmercury (MeHg) continued to accumulate IHg in the brain 6 months after the MeHg dosing had stopped. This clearance group showed a significant increase in microglial activity in the brain. Results from mercury speciation of the brain in these primates showed that MeHg concentration plateaued at about 12 months while the IHg fraction, derived from the demethylation of MeHg, continued to increase 6 months later. Autometallographic determination of the distribution of IHg by cell types showed microglial and astroglial cells contained significant more IHg deposits relative to other cells. This data suggests that IHg present in the brain is the toxic agent and responsible for the changes in the microglial and astroglial population (Charleston et al.1996).

The sole conclusion to be drawn from Burbacher, 2005 is, and we quote:

 - “The results indicate that MeHg is not a suitable reference for risk assessment from exposure to thimerosal-derived Hg.”

Which, when applied to Burbacher, 1996, renders any conclusions drawn from this study as irrelevant. Setting that aside for the moment, the Burbacher, 1996 study used more than 5 times the concentration of mercury before changes in brain cells were observed and those changes looked very different from those reported by Vargas, et al.

So assuming that chronic exposure to methylmercury, not thimerosal, does result in an accumulation of inorganic mercury, Burbacher, 2005 shows a steady decline in the inorganic mercury fraction which never achieves levels required to induce changes in neuroglial populations that may, or may not, be associated with autism in some individuals.
 
If Mr. Wagnitz wants to make a case for an hypothesis involving chronic inorganic mercury accumulation in the brain eventually leading to neuroglial activation, eventually leading to autistic like behaviors, Mr. Wagnitz will have to exclude reports of early and immediate regression following exposure to thimerosal containing vaccines (which we thought would be the opposite of his purpose for writing).

Chronic microglial activation is recognized as an important component of neurodegenerative disease and neuroinflamation and contributes to neuronal dysfunction and injury. The recognition of microglial as the brains immune system and the understanding that chronic activation of this system leads to pathological consequences, has been the primary explanation for the current concept known as neuroinflamation (Streit et al. 2004).

True. When, and only if, neuroinflammation is recognized and accepted to be a component of autism, scientists can look at toxic exposures as potential contributing factors as they continue to do for many neurological disorders where neuroinflammatory processes are suspected.

In a 2005 study brain tissue was obtained during autopsy from autistic patients. The author’s data show an active neroinflamatory process in the cerebral cortex, white matter and in the cerebellum of autistic patients. Immunocytochemical studies showed marked activation of the microglial and astroglial cells (Vargas et al. 2005).

This appears accurate more or less, but is there any reason to suspect mercury in any form as the responsible agent? Given the myriad substances and infectious agents capable of inducing microglial activation, why suspect a single agent? Again, Burbacher’s early work showed patterns of changes in these cell populations inconsistent with mercury toxicity. In fact many agents produce distinctive effects on these cells, though nothing approaching a unique signature. Microglial activation can be observed during the early stages of mammalian neurodevelopment which, by Mr. Wagnitz’ line of reasoning, would indicate infancy is caused by thimerosal exposure.

Another piece of the puzzle is provided in a recently published study comparing mercury brain levels in infant Macaca fascicularis primates exposed to injected ethylmercury and infant Macaca fascicularis primates exposed to equal amounts of ingested methylmercury (Burbacher et al. 2005). Primates exposed to the ethylmercuy retained twice as much IHg in their brains in comparison to the methylmercury exposed primates. These primates were exposed to mercury levels at a rate equal to what children in the United States received via standard childhood vaccines from 1991- 2003.

A piece, perhaps, but to which puzzle? Taken the way Mr. Wagnitz has recited this frequently misinterpreted study, one might draw the conclusion that exposure to equimolar concentrations of Methylmercury and thimerosal will predictably result in double the deposition of absolute inorganic mercury in the brain. Let’s look at the actual study to see if that’s the case. From the abstract:

 - “Brain concentrations of total Hg were significantly lower by ~3-fold for the thimerosal-exposed infants when compared to the MeHg infants, while the average brain-to-blood concentration ratio was slightly higher for the thimerosal-exposed infants (3.5±1.0 vs. 2.5±0.6). A higher percentage of the total Hg in the brain was in the form of inorganic mercury for the thimerosal-exposed infants (34% vs 7%).”

This study can be interpreted a little differently than apparently done so by Mr. Wagnitz. It can be read to mean that exposure to equivalent amounts of MeHg and thimerosal will result in three times the concentration of total mercury in the brain in the group exposed to MeHg. Or, one-third the amount from exposure to thimerosal compared to MeHg - not exactly double. Of that one-third total mercury, a higher fraction was present as the inorganic variety.

Additionally, the statement Wagnitz makes implying that there would have been a consistent mercury dose via vaccination through 2003 seems like it could be less than accurate:

 - “…N.I.P. estimated the amount of thimerosal in provider vaccine inventories in a survey conducted September 20, 2001 to February 20, 2002. The targets were a convenience sample of providers getting site visits from public health officials across the country. Inventory counts were done of all refrigerators for D.T.a.P., Hib, and hep B pediatric vaccines. The thimerosal classification was based on the lot number information, which was verified by the manufacturers. In September 2001, 225 sites were canvassed, and 447 by February 2002…During the visits, the providers were surveyed about thimerosal-containing vaccines in their inventories. Of the 447 interviews, 83.5 percent reported no thimerosal-containing vaccines in stock at any time since October 2001.”

Empahsis is ours. Source: CENTERS FOR DISEASE CONTROL AND PREVENTION ADVISORY COMMITTEE ON IMMUNIZATION PRACTICE, Records of the Meeting Held on February 20-21, 2002, Atlanta Marriott North Central Hotel, Atlanta, Georgia.

This study did not take into account additional ethylmercury exposure from Rho D immunoglobulin injections that children of Rh negative mothers would have received during pregnancy nor does it look at mercury excretion issues.

Childhood vaccines have been thimerosal-free or contain only trace amounts in the U.S. for well into 5 or 6 years now. Autism diagnoses continue to increase. If impaired mercury excretion does play a role in autism, science has yet to report it that we can see.

While the Vargas study did not involve the testing for mercury, this future research, if undertaken, could provide a valuable piece to this puzzle.

Perhaps, but drawing conclusions along the way that are not supported by existing data (and are actually hypotheses, as in the case of Holmes et al.), seems more like pretending some key pieces are present, when in fact they may not even exist. Judging by the frequency with which Wagnitz cites Burbacher, his hypothesis seems entirely dependent on some unique properties of thimerosal and/or ethylmercury to deposit unusually high concentrations of inorganic mercury in the CNS, subsequently triggering microglial activation-dependent autism. In case he hasn’t heard, very few folks are thinking about thimerosal as a sole source of exposure, and many are now looking toward environmental sources that are predominantly methylmercury. Even an apparent point of origin of his hypothesis - the Holmes et al. “First Baby Haircuts” study (thought by many to be the source of the ‘poor excretor’ hypothesis) attempted to estimate (not measured, as claimed in their paper) exposure from other mercury sources, such as dental amalgams and maternal seafood consumption.

Of course, we could ignore what the evidence-to-date (or lack thereof) shows us about autism so far. We could just take Mr. Wagnitz’s word for it that his only connection to autism is that his daughter has been labeled as such so ‘they’ can refuse paying for proper medical care and instead push dangerous anti-psychotic drugs on her. We could also take Mr. Wagnitz’s word for it that autism, for 90% of cases, is nothing but a word used to cover-up the damage done by thimerosal to millions of kids. Given the apparent scarcity, weakness, and disconnectedness of the evidence presented so far, all we’d need to do is say, “we believe”. But that’s just not our style.

Selected Further Reading

Gernsbacher MA, Dawson M, & Goldsmith HH.
Three reasons not to believe in an autism epidemic.
Current directions in psychological science. 2005;14(2):55-58.

Bernard S, Enayati A, Redwood L, Roger H, Binstock T.  
Autism: a novel form of mercury poisoning.
Med Hypotheses. 2001 Apr;56(4):462-71.

Nelson KB, Bauman ML.
Thimerosal and autism?
Pediatrics. 2003 Mar;111(3):674-9.

Left Brain/Right Brain Blog Autism Wiki
Bernard
http://www.kevinleitch.co.uk/wiki/Thimerosal/Bernard

Holmes AS, Blaxill MF, Haley BE.
Reduced levels of mercury in first baby haircuts of autistic children.
Int J Toxicol. 2003 Jul-Aug;22(4):277-85.

Burbacher TM, Shen DD, Liberato N, Grant KS, Cernichiari E, Clarkson T. 
Comparison of blood and brain mercury levels in infant monkeys exposed to methylmercury or vaccines containing thimerosal.
Environ Health Perspect. 2005 Aug;113(8):1015-21

Charleston JS, Body RL, Bolender RP, Mottet NK, Vahter ME, Burbacher TM. 
Changes in the number of astrocytes and microglia in the thalamus of the monkey Macaca fascicularis following long-term subclinical methylmercury exposure.
Neurotoxicology. 1996 Spring;17(1):127-38.

Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. 
Neuroglial activation and neuroinflammation in the brain of patients with autism.
Ann Neurol. 2005 Jan;57(1):67-81.
Erratum in: Ann Neurol. 2005 Feb;57(2):304.

C. Hooper, J. M. Pocock
Focus on Microglia
http://www.abcam.com/index.html?pageconfig=resource&rid=10353&pid=7

The Legend Of The “Poor Excretors”
http://www.autismstreet.org/weblog/?p=103

Undead Bad Science
http://photoninthedarkness.blogspot.com/2006/03/undead-bad-science.html

An Old New Twist on Undead Bad Science?
http://www.autismstreet.org/weblog/?p=61

A Perfect Example of how NOT to do a Study - Part One
http://photoninthedarkness.blogspot.com/2005/07/pefect-example-of-how-not-to-do-study.html

A Perfect Example of how NOT to do a Study - Part Two
http://photoninthedarkness.blogspot.com/2005/07/perfect-example-of-how-not-to-do-study.html

Dr. Amy Holmes was just trying to help
http://autismdiva.blogspot.com/2005/12/dr-amy-holmes-was-just-trying-to-help.html