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Autism Omnibus and shrinking hypotheses

13 May

The number of people who have made confident assertions about thiomersal causing autism over the last four years or so is astounding.

It’s now 2005…..[W]e should see fewer cases entering the system this year than we did last year.

– David Kirby

if the total number of 3-5 year olds in the California DDS system has not declined by 2007, that would deal a severe blow to the autism-thimerosal hypothesis…..total cases among 3-5 year olds, not changes in the rate of increase is the right measure.

– David Kirby

“Late 2006 should be the first time that rates go down” said Handley. “If they don’t, our. hypothesis will need to be reexamined.”

– JB Handley

…I would like to make a virtual wager that within the next 18-24 months scientific evidence will make the thimerosal-autism link a near certainty.

– Richard Deth, March 22, 2006.

All these statements have one thing in common, they promote the idea that mercury (thiomersal in particular) causes autism in either all, or the vast majority of cases.

However, listening to the Autism Omnibus yesterday provided a very interesting change from this perspective:

In some kids, there’s enough of it that it sets off this chronic neuroinflammatory pattern that can lead to regressive autism,” said attorney Mike Williams.

ABC.

Note the new language: ‘some kids’….’regressive autism’…..’can lead’.

It seems the days of ‘all autism is mercury poisoning’ are long gone.

Petitioners presented a very interesting expert witness yesterday – a Dr Sander Greenland from UCLA who is a Professor of Epidemiology.

Dr Greenland argued some strange facts for the PSC but completely in line with this new tack that I can’t even remember being argued in the Cedillo hearing (thiomersal may cause regressive autism in some kids).

Greenland essentially argued that all the current epidemiology regarding autism and thiomersal was not good enough to detect thiomersal causation in regressive autism – this is from his submitted report:

A simple example may clarify this point. If a vaccine is not associated with any type of disorder in the category, we should expect to see the same risk when comparing vaccinated to the unvaccinated. Suppose, however, that in reality the vaccine is associated with a two-fold increase in the risk of a type of disorder in the category, but not associated with any other type. Suppose also that, without the vaccine, the associated type represents only one-tenth (10%) of the disease category, and that the total number of cases in the category would be 100. Then, without the vaccine, the number of cases with the associated type would be 100/10 = 10. With the vaccine, however, the number of cases with the associated type would double, to 20, an excess of 10 cases over the original 10 with the associated type. This excess produced by the vaccine would result in a total of 100+10 = 110 cases over the full category, which is only a 10% increase in the risk of any type in the category. Thus, the risk ratio for getting any type in the category would be only 110/100 = 1.1. Such a small risk ratio cannot be reliably distinguished from 1 by ordinary epidemiologic studies.

In other words, the amount of autism caused by vaccines is in fact too small to be detected by epidemiology. If, of course, it is associated with it at all – a point made later by Dr Greenland:

The brief overview given above supports the idea that the association of MCV (mercury containing vaccine) with autism is small or nonexistent.

But really his point is that if thiomersal does cause autism (and whilst he professes to have ‘no opinion’ on the matter it may be telling that he refers to the idea as a hypothesis throughout his report, not a theory) it causes it in very, very small numbers indeed.

Dr Greenland passed no opinion the validity of the hypothesis itself. Rather, he was there to study epidemiology. We have to respect his opinion even if we disagree with it.

The more telling aspect for me was this sudden conversion from ‘vaccines cause autism’ to this suddenly tiny percentage – so small to be undetectable by epidemiology up to this point. That’s quite a step back. What will become of the Omnibus cases that are not considered’ regressive’? Or the ones (like Michelle Cedillo) who were claimed to be regressive but were, upon viewing the video evidence, clearly not. Are the PSC really throwing cases away?

Association Between Autism and Environmental Mercury Exposure Disappears Once Population Density is Controlled for

2 May

california-pollution-autism-analysis

[Correction 5/4/2008: Please see this comment. The trends and conclusions don’t change. The scatter of the graphs is not affected in a way that is noticeable, but the Y ranges do change. The adjustment formula also changes. See the corrected spreadsheet for details.]

This is a critique of Palmer et al. (2008), a recent study claiming to associate the administrative prevalence of autism in Texas school districts and proximity to coal-fired power plants, as well as mercury emissions. Normally I would just point out the likely problems of the paper, but this time I will go further and test a key hypothesis of my critique using California data in a way that is straightforward enough for readers to verify.

Background

Palmer et al. (2008) is not the first study of its kind. Palmer et al. (2006) claimed to document that “for each 1000 lb of environmentally released mercury, there was a 43% increase in the rate of special education services and a 61% increase in the rate of autism.” The more recent paper by Palmer et al. does not result in such remarkable estimates, considering its finding that “for every 1,000 pounds of release in 1998, there is a corresponding 2.6 percent increase in 2002 autism rates.”

Windham et al. (2006) is a case-control study done in the San Francisco Bay Area which claims to associate autism with emissions of Hazardous Air Pollutants (HAPs).

Then we also have Waldman et al. (2007), which I consider a study of the same type, except it associates autism with precipitation (as a proxy of television exposure) instead of environmental pollution.

My primary criticism of these types of studies is that they are attempting to find a cause for an epidemiological phenomenon that could very well not require an environmental explanation. That is, administrative data (special education data in particular) is not equipped to tell us if there are real differences in the prevalence of autism from one region to the next. No screening has ever demonstrated that substantial differences in administrative prevalence between regions are not simply diagnostic differences.

That said, the studies have been done, and they have found statistical associations. This usually means they either found a real effect or they have failed to properly control for some confound.

As I have noted repeatedly over the last couple of years, the glaring confound that most likely mediates these types of associations is urbanicity. The association between urbanicity and autism was documented even before these studies were carried out. It is plausibly explained by a greater availability of autism specialists in urban areas and by greater awareness in the part of parents who live in cities.

Palmer et al. (2008) does control for urbanicity, which might be one of several reasons why its findings are underwhelming compared to those of Palmer et al. (2006).

Is the control for urbanicity in Palmer et al. (2008) adequate?

There are two main problems with the control for urbanicity, described in the paper as follows.

Urbanicity. Eight separate demographically defined school district regions were used in the analysis as defined by the TEA: (1) Major urban districts and other central cities (2) Major suburban districts and other central city suburbs (5) Non-metropolitan and rural school districts In the current analysis, dummy variables were included in the analysis coding Urban (dummy variable 1, and Suburban (dummy variable2), contrasted with non-metro and rural districts which were the referent group. Details and specific definitions of urbanicity categories can be obtained at the TEA website http://www.tea.state.tx.us/data.html

.

1. It is too discrete. Within the set of urban districts, some districts will be more urban than others. The same is true of rural districts. Palmer et al. (2008) is effectively using a stratification method to control for urbanicity, but this method is limited, especially considering the paper looks at 1,040 school districts. A better methodology would be to use population density as a variable.

2. Modeling for distance. The paper models autism rates based on distance to coal-fired power plants. It follows that a control variable should model distance to urban areas rather than urbanicity of each district. Granted, this would not be easy because, as noted, urbanicity is not a discrete measure. But it needs to be noted as a significant limitation of the analysis. Consider school districts in areas designated as “rural” that are close to areas designated as “urban.” Such proximity would presumably provide access to a greater availability of autism specialists than would otherwise be the case.

California Analysis

This time around I thought it would be a good idea to run some actual numbers in order to test this population density confound hypothesis that up to this point has been simply theoretical. I will use county-level data from the state of California, which was fairly easy to obtain on short notice. The data used is the following.

  • Special education autism caseload data at the county level for 2005 was obtained from a California resident who had requested it from the California Department of Education.
  • County population and density data for 2006 was obtained from counties.org.
  • Atmospheric mercury concentration data was obtained from the EPA’s 1996 National Air Toxics Assessment Exposure and Risk Data for 2006.
  • All of the raw data, intermediate data, formulas, and resulting charts can be found in this spreadsheet which I am making available for readers to verify and tweak as needed.

Population Density vs. Autism

Autism prevalence was calculated by dividing the special education autism caseload of each county by its population (Column G). This is not a precise determination, of course, but it should not affect the analysis. In any given California county, the population under 18 is roughly a fifth of the total population of the county.

A first attempt at modeling population density vs. autism prevalence (Chart A) suggested the relationship was logarithmic. So I modeled log(population density) vs. autism prevalence, which resulted in the clear correlation you see in Figure 1 (Chart B).

Pop. Density vs. Autism Prevalence

Figure 1: Pop. Density vs. Autism Prevalence

–

This is as expected. You will note, however, there is one significant outlier in the lower-right quadrant. That is San Francisco county. Presumably, because of its peculiar geographic characteristics, its population density is the highest in the state. Nevertheless, San Francisco is an important data point since it is a significant urban area which happens to have a relatively low special education prevalence of autism. Let’s leave it in and see how it affects things.

I will use a simple standardization method of adjustment for population density. Basically, I will standardize autism prevalence in each county, such that population density is no longer a factor. Think of it this way. If the population density of each county grew such that its log were now about 3.5, how would we expect autism prevalence to be affected? The following formula is what I came up with.

Adjusted(Y) = Y + 7 – 1.93 * X

The fact that the adjusted prevalence (Column H) is not dependent on population density can be verified graphically (Chart C). Readers can click back and forth between Chart B and Chart C to better understand the effect of the adjustment. I will come back to this adjusted prevalence.

Mercury Exposure Concentration vs. Autism

I obtained atmospheric mercury exposure concentrations for each county from 1996 EPA data (Column I). More recent data would’ve been better since our population density data is from 2006, but it is not clear if newer data is available. I learned of the 1996 data because that is what Windham et al. (2006) uses. I’m working under the assumption that changes in population density in the last decade have been roughly uniform across the state.

Let’s first look at Figure 2 (Chart E), a graph of log(mercury exposure) vs. autism prevalence, without adjustment for population density.

Pop. Density vs. Autism Prevalence

Figure 2: Mercury Exposure vs. Autism Prevalence

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There is a graphically noticeable trend in Figure 2, which is not surprising. The question is, does the trend remain after adjustment for population density?

Pop. Density vs. Autism Prevalence

Figure 3: Mercury Exposure vs. Autism Prevalence Adjusted For Pop. Density

–

Figure 3 (Chart D) is a graph of log(mercury exposure) vs. standardized autism prevalence; that is, autism prevalence adjusted for population density as previously calculated. In this figure we see there’s no longer a graphically discernable correlation between environmental mercury and autism. In fact, Excel produces a linear fit that indicates there’s somewhat of an inverse correlation between environmental emissions and autism prevalence.

Granted, if we were to remove San Francisco as an outlier, the trend would be pushed upwards. But then in this graph there appear to be two additional outliers in the middle upper part of the graph, Orange county and Los Angeles county. Keep in mind we have not adjusted for wealth. Regardless of how we might adjust the analysis, I fail to see that the graph would support a statistically meaningful association between mercury exposure and autism.

Further Confirmation

So far I have provided evidence that, in California, an association between environmental mercury exposure and autism disappears once we control for population density. This is clear to my satisfaction, but I thought it would be a good idea to attempt an inverse exercise as an illustration of the adjustment method. That is, let us try adjusting prevalence for mercury exposure, and see if the correlation with population density remains.

This is similar to what I did previously. A linear model is discerned from the correlation between log(mercury exposure) and autism (Chart E). This is used to derive an adjustment formula (Column K) whose validity can be verified graphically (Chart F). The new adjusted prevalence (Column K) is used in a new graph of log(population density) vs. autism: Figure 4 (Chart G).

Pop. Density vs. Autism Prevalence

Figure 4: Pop. Density vs. Autism Prevalence Adjusted For Mercury Exposure

–

What Figure 4 (Chart G) tells us is that even after we control for mercury exposure, there is still a clear correlation between autism and population density. In other words, population density wins bigtime – I believe that is the epidemiological term.

Conclusion

An analysis of California data suggests that correlations between the administrative prevalence of autism and environmental mercury emissions are fully mediated by population density. Palmer et al. (2008) suggests there is a real effect in Texas, but its results are not convincing primarily because its control for urbanicity is limited and inconsistent with the hypothesis the paper tests.

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Alexander Krakow – The Next Bombshell

27 Apr

And so, the next twist in the Autism Omnibus is revealed. Writing in Spectrum Publications in a piece rather hopefully entitled ‘The Next Hannah Poling’ David Kirby writes:

….the boy who was selected to replace Hannah Poling as the first-ever thimerosal “test case” in so-called Vaccine Court, has just been found with many of the same unusual metabolic markers as… you guessed it, Hannah Poling.

……..

….the court announced that the replacement thimerosal test case was also being withdrawn, in order to “proceed to an individual hearing on a different theory of causation.”

……..

“We want to pursue an additional theory, not a different theory,” the boy’s father told me. “We are by no means abandoning the thimerosal theory of causation but, in the context of the test case, the thimerosal theory would have eclipsed our other evidence, including evidence of metabolic dysfunction,” such as impaired mitchondria and low cellular energy.

The boy is Alexander Krakow, son of EoH regular, lawyer Bob Krakow. Up until very recently, lawyer Bob could be heard trumpeting the evils of thiomersal to the exclusion of just about everything else (MMR aside of course). Now, however, the Krakow’s have a new hypothesis (DK refers to ‘theory’ through his article but it isn’t a theory) – but note they still give a shout out to thiomersal anyway.

Now, much as DK and the Krakow’s might want to think this is important, it really isn’t. This situation is in no way similar to Hannah Poling’s. In that scenario, HHS said she was vaccine damaged (but again, despite what DK says, there was no concession she had been made autistic by her vaccines – an opinion the medical evidence and mitochondrial experts agree with) and they recommended awarding damages uncontested. In Alexander Krakow’s case, his _parents_ have withdrawn him from the Omnibus. No science has been presented, HHS have not said anything at all about his medical conditions. All we have so far is the Krakow’s opinion that their son has a mitochondrial disorder.

This is especially interesting in the light of the report of the Krakow’s own hand-picked medical expert, DAN doctor Elizabeth Mumper – not only _a_ DAN! doctor but the ‘Medical Director’ of ARI.

This report prepared by Mumper states:

In my best professional judgement…..it is more likely than not that the thimerosal in the childhood vaccines Alexander Krakow received was a substantial contributing factor to his neurodevelopmental problems.

So the ARI medical director blames thiomersal. What did she have to say about mitochondria?

Well, nothing. The word ‘mitochondria’ is not mentioned once in the whole report.

In his article DK talks about Alexander Krakow having the same ‘markers’ as Hannah Poling. He neglects to say what they are however, or how he concludes they are markers. He also neglects to mention how the DAN! medical director singularly failed to detect any of these so called ‘markers’.

Perhaps the biggest mark against Alexander Krakow having ‘mito induced autism from vaccines’ is the fact that his medical report (which stated the thiomersal dunnit) made no mention of a fever or raised temperature. If I recall correctly, it was a key part of the Hannah Poling scenario that the vaccines had given her a fever and it was this which aggravated her underlying mitochondrial disorder and in turn caused her autism. Alexander Krakow’s medical report mentioned no fever at all.

David must also be aware of the fact that the ‘markers’ he refers to are, at best, markers of mitochondrial issues. Lots kids with mito issues have them. They bear no relation to vaccine injury. I was disappointed to see this issue being talked around but I have some hopes that later this year – towards the autumn maybe – this issue will be made abundantly clear.

So, all in all I am deeply puzzled as to how this is ‘the next bombshell’ or even how Alexander Krakow can be considered to have any kind of mitochondrial related autism issue. The HHS definitely did not concede this case and my guess is that they will be more than happy – given Bob Krakow’s own expert medical report into his son – to contest when their case comes up separately.

My further guess is that we will see some more people switch horses sometime fairly soon. I’m also guessing that – like the Krakow’s – it will be done against their lawyers advice.

Green our vaccines?

21 Apr

Jenny McCarthy:

I am surely not going to tell anyone to vaccinate. But if I had another child, there’s no way in hell…….for my next kid — which I’m never going to have — there’s no way.

Thus speaks the woman who claims she is not anti-vaccine and not intending to spread an anti-vaccine agenda.

In June this year she will be spearheading a rally to carry the message of ‘green our vaccines’. Said message is apparently all about making vaccines ‘cleaner’ (???) reducing the number of them and spacing them out. No scientific reason for this of course.

When asked, the ‘green our vaccines’ leadership claim that they are not _anti_ vaccine – just pro _safe_ vaccine. Uh-huh. And which vaccines are ‘safe’ according to the ‘green our vaccines’ committee? Well, it seems that Jenny McCarthy thinks that answer to that is ‘none’. She will never vaccinate again. No way in hell.

Some people think that the ‘green our vaccines’ message is a trojan horse.

I’m against vaccines, but I feel that “greening our vaccines” is a step in the right direction. Because I realized that more people will be open to hearing the message “green our vaccines” rather than “no more vaccines”. In the beginning I couldn’t imagine scrapping vaccines altogether, but in time I transformed. I think the public
needs to digest this one bite at a time.

Greening of the vaccines is only half of the issue, people need to wake up and see that there is no such thing as a safe vaccine…

I agree with you that there will never likely be a “safe” vaccine, but the only good thing I see about talking about “safer” vaccines, is that this makes it more “palatable” for some and more likely that this news gets out into the mainstream. People are more comfortable dealing with “too much, too soon”, rather than with “none at all”. It gets the vaccine issue a foot in the door, so to speak, into the mainstream media

………..

Hopefully, the “Green Our Vaccines” campaign will get the ball rolling and get this info to more people, to get them thinking and talking about vaccine safety issues. Whether there is such a thing as “safe vaccines” will need to follow after that initial discussion.

….parents do need to come to the conclusion that vaccines are useless and harmful, on their own, through their own thinking and research

I agree that “Green the vacines” is more palatable to the general populace and that is the ‘message’ Jenny and TACA have chosen. I think the approach is ingenious and fits right into the times of global warming and greening everything.

……………

I think green the vaccines ultimately leads to NO vaccines but agreed it must be done in steps.

…………..

We could hopefully all agree that the goal is to STOP damaging children whether that will take greening or incinerating vaccines, that is still the ultimate goal.

These messages are from an active discussion on the EoH Yahoo Group. And after all, why wouldn’t this be the message? Jenny McCarthy quite obviously does _not_ believe in vaccination.

In my opinion the whole ‘green our vaccines’ campaign is very much a trojan horse. We all know how groups associated with this campaign really feel about vaccines. We know how Jenny McCarthy feels about vaccines and we can see what the ‘rank and file’ really think about both vaccines and what the ‘green our vaccines’ campaign is really all about.

Thankfully, the opinion of McCarthy as a less than stellar representative for science is a widely held mainstream one. On Gawker for example, her recent embarrassing performance on Larry King was described as:

Larry King had noted medical expert/softcore video star Jenny McCarthy on the program last night to talk about AUTISM. Specifically, how it’s caused by VACCINATING YOUR CHILDREN. This is patent conspiratorial nonsense, but it’s very popular conspiratorial nonsense. Of course, in a battle between concerned, credulous parents and medical experts, the media will generally frame it as, say, Debate Rages Anew on Vaccine-Autism Link. Faced with a panel of three trained pediatricians, Ms. McCarthy shouted “BULLSHIT” twice.

and Jossip said:

Jenny McCarthy believes common medical vaccinations cause autism in children. And you know what she thinks of your opinions if you disagree? Bullshit! At least that’s what she yelled last night while berating three doctors trying to reason with her on Larry King Live.

Ouch.

Now, whilst it might be mildly amusing to see how real people in the real world (those unconnected with either the vaccine, autism or vaccine/autism debates) consider the opinions of McCarthy it shouldn’t be forgotten or swept aside that its not just about the mercury. Its not even just about the autism. Its about the vaccines. When Jenny McCarthy tells you she wants to ‘green our vaccines’ then ask her exactly what that means and why she won’t ever vaccinate another child of hers.

Frustration

20 Apr

One of the most frustrating things about blogging the unfolding vaccine>mitochondria>autism hypothesis is that a lot of the doctors who are experts in the field of mitochondria don’t want to publicly comment. A lot of them feel quite rightly that there is a certain element who are not the most balanced of individuals and they don’t really want to expose themselves to these people. That I can definitely empathise with.

However it does, as one of them has admitted themselves, leave the field wide open to (and I quote directly from one of these doctors):

….legions of mountebanks eager to pad their retirement funds at the expense of desperate parents…

So when a very well respected mitochondria researcher says the following all I can do is post it and not attribute it and hope that it can be read and believed. Of course, the fact it appears on this blog will no doubt cause some to dismiss it entirely but I would urge them not to do so. Please remember that kids with mitochondrial issues are a whole new ball game. Talking their parents out of vaccinating them could very well kill them.

…..I do not know of any evidence connecting mercury and mitochondrial disease. There is no evidence connecting vaccination with mitochondrial diseases: certainly vaccinations do not cause mitochondrial diseases. Whether they may act as transient stressors, like intercurrent URIs do, remains to be determined. Clearly, energy-challenged children with mitochondrial diseases need to be protected from potentially deadly infections through vaccination.

Mitochondria, autism and thimerosal

18 Apr

The whole mitochondria/autism thing is pretty fascinating. A Dr Shoffner presented the results of a study he conducted (‘Mitochondrial Dysfunction May Play a Role in Autism Spectrum Disorders Etiology‘ – its free registration at Medscape to read the whole thing) in which he noted:

a retrospective analysis of 41 children with ASD who were being evaluated for suspected mitochondrial disease showed that 32 (78%) had defects in skeletal muscle oxidative phosphorylation (OXPHOS) enzyme function and 29 of 39 (74%) harbored abnormalities in the OXPHOS proteins.

The numbers kind of leap out at you don’t they?

Except, we need to remember that this is a heavily skewed population. As SL has pointed out:

I can’t state it enough: this is NOT a random sample of autistic individuals. These are children who were already suspected of having a mitochondrial disorder.

Which is a bit like looking for wet kids at a swimming pool. It doesn’t really tell us anything about autism aetiology. It tells us that some kids who are autistic also have mitochondrial dysfunction. Reading anything concrete into that is just like reading anything concrete into the fact that autism symptoms become clear around the time vaccines are administered – correlation does not equal causation after all.

Dr Shoffner is unavailable right now but I have dropped an email off with him asking if he would be kind enough to make his presentation available. We’ll see.

In the meantime it should be noted that there are other highly respected mitochondrial researchers who are not pleased with the way that Dr’s Poling and Shoffner have conducted themselves. A researcher I am talking with commented:

….more harm than good has been done this time by Shoffner’s and Poling’s whipping up controversy but not providing the hard data that everyone needs….. Therefore, again, I ask that you serve the public good by not trying to ferret out partial data and incomplete statements from me or others, trust that nothing is being hidden by anyone, and wait for the full story to appear in a medical journal……offer assurance to your readers that the true story will be told and that misstatements of the legions of the uninformed and conspiracy mongers who are pursuing their own selfish aims will ultimately be revealed.

Strong words from someone who clearly feels that Shoffner and Poling are doing what they’re doing solely to be controversial.

So that seems to be the state of research regarding a mitochondrial aetiology for autism. Patchy and sensationalist with a clear agenda to serve personal interests.

However, as we all know, there are a group of people who want to take the autism/mito thing one step further and blame vaccines for triggering an occluded mitochondrial dysfunction which in turn causes autism. Its like a minor league domino effect with only three domino’s. Again, it reminds me very much of the early days of the thiomersal/MMR hypotheses – look for a direct cause and when one can’t be found, look for an indirect one and twist, twist, twist until you can argue for one.

Our old friend Ginger Taylor has, for example, been hopping from online newspaper to online newspaper saying in their comments section that:

The debate is over. Our highest health authorities have stated that vaccines are a cause of autism.

When in fact no such statement exists. Ginger is arguing that ‘features of autism’ is the same as a diagnosis of autism. Back in the real world of autism diagnostics, that is not the case.

So – what can we do to examine the hypothesis that thimerosal triggers mitochondrial dysfunction which in turn triggers autism? We could search for papers that mention thimerosal and mitochondria. When we do we get:

1: Yel L, Brown LE, Su K, Gollapudi S, Gupta S.
Thimerosal induces neuronal cell apoptosis by causing cytochrome c and apoptosis-inducing factor release from mitochondria.
Int J Mol Med. 2005 Dec;16(6):971-7.
PMID: 16273274 [PubMed – indexed for MEDLINE]

2: Humphrey ML, Cole MP, Pendergrass JC, Kiningham KK.
Mitochondrial mediated thimerosal-induced apoptosis in a human neuroblastoma cell line (SK-N-SH).
Neurotoxicology. 2005 Jun;26(3):407-16.
PMID: 15869795 [PubMed – indexed for MEDLINE]

3: Makani S, Gollapudi S, Yel L, Chiplunkar S, Gupta S.
Biochemical and molecular basis of thimerosal-induced apoptosis in T cells: a major role of mitochondrial pathway.
Genes Immun. 2002 Aug;3(5):270-8.
PMID: 12140745 [PubMed – indexed for MEDLINE]

4: Collin HB, Carroll N.
In vivo effects of thimerosal on the rabbit corneal endothelium: an ultrastructural study.
Am J Optom Physiol Opt. 1987 Feb;64(2):123-30.
PMID: 3826286 [PubMed – indexed for MEDLINE]

5: Collin HB.
Ultrastructural changes to corneal stromal cells due to ophthalmic preservatives.
Acta Ophthalmol (Copenh). 1986 Feb;64(1):72-8.
PMID: 3083641 [PubMed – indexed for MEDLINE]

6: Van Horn DL, Edelhauser HF, Prodanovich G, Eiferman R, Pederson HF.
Effect of the ophthalmic preservative thimerosal on rabbit and human corneal endothelium.
Invest Ophthalmol Vis Sci. 1977 Apr;16(4):273-80.

Of these, studies 4, 5 and 6 are not relevant – they’re talking about eyes. Its studies 1, 2 and 3 on this list that are articulatory relevant to us in our search for papers touching on vaccines>mito>autism. If anyone else finds any, please let me know in the comments section.

Now, these three studies are not supportive of the vaccines>mito connection. Why? They use frankly massive concentrations of thiomersal, way beyond whats contained in a vaccine. A quote from a scientist about these studies:

all of the studies used “non-physiological” concentrations of thimerosal – concentrations that would not be reached even by giving three or four (or even ten or twenty) high-thimerosal-containing vaccines to a low-weight and/or premature infant.

You can kill mitochondria with glutamate (an amino acid found in chicken soup, among other things), salt, oxygen, and a number of other things, if you use ENOUGH of it. The studies are not relevant…..because the concentrations used are so high – by a factor of at least 100.

So we seem to be back to square one. Whilst the evidence for a mitochondrial aetiology for autism is of mixed provenance and yet seems probable at some level, the evidence for thiomersal and autism-related mitochondrial dysfunction is not good.

Anti-vaccination and autism

16 Apr

I need to reproduce this comment from Amy Tuteur, MD on Autism News Beat. Its perfect.

“How does Dr. Tuteur explain parents who fully vaccinated and trusted the vaccination policy and then became disenchanted with it only after seeing their children seriously injured?”

Disenchantment is not the standard. The scientific evidence is the standard. It is not as though this hasn’t been studied. The purported link between vaccines and autism has been studied extensively and repeatedly. The scientific evidence indicates no difference in the incidence of autism between those who are vaccinated and those who are not. There is also no difference in the incidence of autism between those who received vaccines containing thimerosal and those who did not.

We’ve looked and the link simply isn’t there. That’s not surprising when you consider that the classic descriptions of the onset of autism, elucidated long before the use of multiple vaccines, is exactly the same as the onset of autism today. Vaccines do not increase the incidence of autism. Thimerosal does not increase the incidence of autism. The natural history of autism has not changed since the introduction of vaccines. It cannot be any clearer than that.

The conspiracy theories are a bunch of baloney. In order for there to be a conspiracy, someone must be hiding information. Doctors are vaccinating their children. Vaccine manufacturers are vaccinating their children. Immunologists are vaccinating their children. Who, precisely, is conspiring to keep information from the public and are we really supposed to believe that they would sacrifice their own children just to preserve the conspiracy?

Moreover, it isn’t as though doctors, immunologist and vaccine manufacturers are denying that vaccines have risks. It is well known that vaccines can and will cause small numbers of deaths and cases of brain damage. We have set up a compensation system precisely because we know about and acknowledge these risks. If doctors, immunologists and vaccine manufacturers are forthcoming about the risk of DEATH, isn’t it a bit absurd to suggest that they would hide the risk of autism?

One thing is certain, vaccine rejectionists do not understand immunology. Immunology is extremely complicated, so it’s not surprising that many people don’t understand it. However, the fact that they don’t understand it tells us nothing about immunology or vaccines, just like the fact that most people do not understand Einstein’s theories of general and special relativity tell us nothing about whether they are true.

Autism is a very serious problem. To the extent that we waste time, money, attention and effort on something that is not causing autism, we are diverting time, money, attention and effort from finding the real cause for autism. That is the saddest aspect of this incredibly sad situation.

I also recently read ‘Trusting blindly can be the biggest risk of all’: organised resistance to childhood vaccination in the UK which has some fascinating things to say on the anti-vaccine movement and their history. Consider this:

There is a small but fascinating social history literature which looks at the birth of resistance during this period in the form of groups like the Leicester Anti-Vaccination League and critical publications like the Vaccination Inquirer . Several of the accounts demonstrate the successes of organised campaigns which inspired marches of up to 100,000 people, riots, public burning of effigies of Edward Jenner, and the celebration of martyrs (Beck 1960, Porter and Porter 1988, Durbach 2000)…..Other accounts of this period stress the impressive ability of the anti-vaccinators to harness the power of the press (Howard 2003) and the important role of key individuals in pushing forward the movement.

Sounds familiar huh?

An Open Letter To The Poling’s

12 Apr

Dear Poling family,

Let me first start by saying that your little girl is beautiful. I am father to two girls (as well as one boy, young man now actually) so I know how great it is to have such wonderful little people around.

I read Jon Poling’s commentary in the AJC and I have to say that I was very disappointed by the level of accuracy in the piece. For example, he says:

On Nov. 9, 2007, HHS medical experts conceded through the Department of Justice that Hannah’s autism was triggered by nine childhood vaccinations administered when she was 19 months of age…

Now I have taken a keen interest in your families case since it became clear what the situation was. I _think_ I have read most of the newspaper reports available online as well as (more importantly) the HHS document itself and (even more importantly) the case study co-authored by Andrew Zimmerman and Jon Poling.

Nowhere, I repeat, nowhere, have I seen anyone from either the HHS, CDC, US Government, or even the Zimmerman/Poling case study say that ‘Hannah’s autism was triggered by nine childhood vaccinations’.

I have seen David Kirby refer to this several times. I have heard lots of people refer to these statements as if they are true and now I hear you doing it too.

But where is this concession?

In what legal, scientific or medical document does it state unequivocally that ‘Hannah’s autism was triggered by nine childhood vaccinations’?

You are a family on the cusp of storm. You need to take more care with your statements. People all over the world are listening. The *fact* as of right now is that no one has conceded ‘Hannah’s autism was triggered by nine childhood vaccinations’. Simply stating it as if it were true does not make it true.

The HHS expert documents that led to this concession and accompanying court documents remain sealed, though our family has already permitted release of Hannah’s records to those representing the almost 5, 000 other autistic children awaiting their day in vaccine court.

Now this confuses me on two levels. Firstly, Special Masters have already said that:

….in the case that is the subject of the media reports, if the parties who supplied documents and information in the case provide their written consent, we may then be able to appropriately disclose documents in the case.

It sounds to me like Dr Poling is trying to turn something around onto the HHS without justification. Maybe your legal team haven’t told you about this news. I understand they’re very busy of late.

The second part of Dr Poling’s statement that confuses me is the allusion to the records being released ‘to those representing the almost 5, 000 other autistic children’.

I thought that you wanted your documents to be made entirely public? Are you now saying you only want the legal teams of the other omnibus lawyers to have access to them?

I would also like to draw your attention to the email I sent to Terry Poling on March 5th asking why the Poling family had not cleared Dr Andrew Zimmerman from speaking publicly about the case. Does the Poling fmaily have any intention of lifting that embargo any time soon?

Dr Poling goes on:

Emerging evidence suggests that mitochondrial dysfunction may not be rare at all among children with autism. In the only population-based study of its kind, Portuguese researchers confirmed that at least 7.2 percent, and perhaps as many as 20 percent, of autistic children exhibit mitochondrial dysfunction. While we do not yet know a precise U.S. rate, 7.2 percent to 20 percent of children does not qualify as “rare.” In fact, mitochondrial dysfunction may be the most common medical condition associated with autism.

This is very disingenuous Dr Poling. I am not sure if you are purposefully distorting the truth or simply not as knowledgeable as you think. In point of fact the figure of 7.2% is from a 2005 study ‘Mitochondrial dysfunction in autism spectrum disorders: a population-based study‘. This is _not_ (as you state) ‘the only population-based study of its kind’. It was in fact a precursor to a _second_ follow up study by the same lead researcher correcting his own data.

This second study (published October 2007) is called ‘Epidemiology of autism spectrum disorder in Portugal: prevalence, clinical characterization, and medical conditions’.

This study declares a 4.1% figure. It is disingenuous in the extreme to refer to old science when newer, more accurate science exists on the subject (and by the same author no less!).

Further, as far as I can tell, the figure of 20% has but one source – a non published summary for attendees of a 2003 LADDERS conference in Boston, USA. Therefore it has not been subject to any kind of peer review. That’s not to say the figure is wrong, merely that it hasn’t been verified or undergone any kind of the usual scientific checks and balances a published piece of work must undertake to ensure quality. This is not ’emerging science’ Dr Poling. Its a set of program notes.

Further, as I understand it from talking to people involved in all three of these different items, the percentages you talk about are expressed percentages _of regressive autism only_ . Now I might have that wrong but I’m pretty sure that’s what was communicated to me.

Taking this into account, when Dr Poling states that:

In fact, mitochondrial dysfunction may be the most common medical condition associated with autism..

and he goes on to suggest population numbers between 10,000 (1%) , 72,000 (7.2%) and 200,000 (20%) of the autistic population he estimates at one million in the US, he is incorrect.

However, if I have understood what is said to me then we need to look at regressive autism numbers only, which are estimated to account for 25%-30% of autistic people. Therefore we are looking at not 7.2% or 20% (one is incorrect, one is not scientifically justified) of one million. We are actually looking at 4.1% (the only scientifically valid number) of between 25 – 30% of one million. Lets take the upper figure of 30%. This gives us a population of 300,000 for regressive autism. Applying the 4.1% estimate we can see that – at best and only if this data is all correct – mitochondrial autism may affect about 13,000 autistic people – 1.3%. If we took the lower range of 25% for regressive autism, we barely get over 1% (10,250).

Secondly, it should be noted that approximately 40% of autism can be accounted for genetically. This already makes it the single largest established cause(s).

Dr Poling goes on to say:

Today there is no doubt that mitochondrial dysfunction represents a distinct autism subpopulation biological marker.

This is true. However, prefacing this sentence with the word ‘today’ gives the highly misleading impression that autism has been associated with mitochondrial disorders and/or dysfunctions only since Hannah Poling came into out collective conciousness. This is far from the case. I can find instances in the scientific literature going back to 1986, over 20 years ago discussing mitochondria and autism and a PubMed search for ‘mitochondrial autism’ yields 34 quality papers published over a 20 year period. This is hardly a new thing Dr Poling.

As a neurologist, I have cared for those afflicted with SSPE (a rare but dreaded neurological complication of measles), paralytic polio and tetanus. If these serious vaccine-preventable diseases again become commonplace, the fault will rest solely on the shoulders of public health leaders and policymakers who have failed to heed the writing on the wall (scribbled by my 9-year old daughter).

I fear that this is projection. You are very close to pushing an anti-vaccine agenda Dr Poling and indeed Terry Poling was active an the Yahoo Group ‘Recovered Kids’ from at least Summer 2001 where she says things like:

Really, the only way to obliterate a disease is to vaccinate everybody – or at least so “they” say

Sept 2001.

Had I told the hospital staff she was autistic they would not have believed me. The same held true for a (sic) educational consultant who came to evaluate hannah the day before the fever started. She said in her report she saw absolutely no autistic behaviors.

Nov 2001.

She has mitochondrial disease which causes her autism.

March 2004.

I do know docs that speak for drug companies but they cover all the meds for a particular disease in their talks with other docs. If they do not agree that the drug is best for certain conditions on the whole they say so.

Feb 2003.

…it [autism] is a DSM set of symptoms. When the symptoms disappear you cannot say the child still has autism…..

Oct 2001.

So Dr Poling when you try to lay the blame for vaccine preventable injuries increasing at the foot of those agencies assigned to try and stop them reappearing I think that is farcical. To me it is clear that the main responsibility lies with those who shun what are by and large safe safe vaccines on the strength of a hypothesis that is nowhere _close_ to scientific truth. I urge you to read this article and the comments left by readers. Its clear who they see as responsible. For example:

Don’t want to vaccinate your kids? Fine with me. Just don’t send them to school where they then put my kids at risk because of your decision.

You are deluding yourself if you think you can turn responsibility for shunning vaccines back on health agencies Dr Poling.

All in all Dr and nurse Poling I think that your public use of misinformation and erroneous science to make your point will serve you no good in the long run. I also continue to be puzzled by your refusal to ‘ungag’ Andrew Zimmerman. I hope you can start to realise that what has ‘happened’ to Hannah is far from remarkable. Best wishes from one autism parent to another.

The Next Big Autism Bomb?

28 Mar

Over on the Huffington Post, David Kirby has posted about The Next Big Autism Bomb. Its a very long post so take a sammich.

The gist (with apologies to Mr Kirby) of it is that there was a conference call to discuss the autism/mito issues:

On Tuesday, March 11, a conference call was held between vaccine safety officials at the US Centers for Disease Control and Prevention, several leading experts in vaccine safety research, and executives from America’s Health Insurance Plans, (the HMO trade association) to discuss childhood mitochondrial dysfunction and its potential link to autism and vaccines.

The purpose of the call was:

“We need to find out if there is credible evidence, theoretically, to support the idea that childhood mitochondrial dysfunction might regress into autism,” one of the callers reportedly told participants.

To that end, Mr Kirby mentions four studies throughout the rest of his piece. Three are accessible but the fourth is a total mystery. This is unfortunate as it is this fourth one which the majority of his blog post relies upon for its conclusions.

The first three are discussing what the prevalence of mito _within_ autism might be. Kirby states:

CDC officials were made aware of a Portuguese study, published last October, which reported that 7.2% of children with autism had confirmed mitochondrial disorders. The authors also noted that, “a diversity of associated medical conditions was documented in 20%, with an unexpectedly high rate of mitochondrial respiratory chain disorders.”

There is a slight point of confusion to clear up here. The figure of 7.2% is from a 2005 study ‘Mitochondrial dysfunction in autism spectrum disorders: a population-based study‘.

The study (by the same author) that Kirby mentions as being published last October is ‘Epidemiology of autism spectrum disorder in Portugal: prevalence, clinical
characterization, and medical conditions‘ declares a 4.1% figure.

The reason for this is that the lead author re-examined his data from the 2005 study and adjusted it downwards in the 2007 study. So Kirby is not correct to state that the authors believe that the rate is 7.2%. The latest figure from these authors is 4.1%.

The third study that discusses prevalence is referenced by Kirby as:

They also know that some reports estimate the rate of mitochondrial dysfunction in autism to be 20% or more. And the rate among children with the regressive sub-type of autism is likely higher still.

Kirby links to a web page that is the web interface to a mail list.

Upon searching for this paper I couldn’t find it anywhere. It is not in PubMed or Google Scholar and in fact I can only find three references to it online at all.

It since transpires that this paper is not in fact a paper at all and has not been published anywhere. It is in fact a summary for attendees of a 2003 LADDERS conference in Boston, USA. Therefore it has not been subject to any kind of peer review. That’s not to say the figure is wrong, merely that it hasn’t been verified or undergone any kind of the usual scientific checks and balances a published piece of work must undertake to ensure quality.

Its also been explained to me that the percentage of “mitochondrial autism” reported by any group will vary with the percentage of regressive autism in their ASD population. So it is not true that the summary states a differential between autism and regressive autism. Rather that “mitochondrial autism” exists _within_ regressive autism.

And so we move on to the fourth study.

One doctor reported his findings from a five-year study of children with autism, who also showed clinical markers for impaired cellular energy, due to mild dysfunction of their mitochondria.

The biochemistry of 30 children was studied intensively, and in each case, the results showed the same abnormalities as those found in Hannah Poling, participants said. Each child had moderate elevations or imbalances in the exact same amino acids and liver enzymes as Hannah Poling.

All thirty children also displayed normal, healthy development until about 18-24 months of age, when they quickly regressed into clinically diagnosed autism (and not merely “features of autism”), following some type of unusual trigger, or stress, placed on their immune system.

……….

But what causes the stress? That is a very big question.

Apparently, in only two of the 30 cases, or 6%, could the regression be traced directly and temporally to immunizations, and one of them was Hannah Poling. In the other cases, there was reportedly some type of documented, fever-inducing viral infection that occurred within seven days of the onset of brain injury symptoms.

Mr Kirby makes this study the raison d’etre of the rest of his post.

I have some major concerns about this. Who is this doctor? What is this study? Where is it published? Where can we _read for ourselves_ what this study says? Without wishing to question the honesty with which Mr Kirby is posting, its obvious that – even in this post as I discuss above – errors and misinterpretations have crept in.

Lets be honest here. These are some *major* claims being made. Firstly that all 30 kids in the study regressed into clinically diagnosed autism as opposed to features of autism. All 30? That’s incredible.

Secondly that 6% of the regressions into clinically diagnosed autism are traced directly from immunisations. That’s big. That is about as big as it gets. I would really like to see this study.

I have asked (twice) in the comments section of Mr Kirby’s post to be pointed to this study. So far, no answer has been forthcoming from anybody.

However. I note that Mr Kirby states that one of the 6% is Hannah Poling. If this is so then it is not true to say that:

the…[autistic]…regression…[can]… be traced directly and temporally to immunizations

(insertions mine for clarity).

As I’ve discussed before, none of the listed symptoms attributed to immunisations can accumulate to a diagnosis of autism. So unless we can actually see this study, know who the author, see what checks and balances this paper has undergone, we’re in a bit of a limbo.

Dear CDC

26 Mar

I read with interest Dr Schuchat’s opinion piece in the AJC today.

Whilst it is gratifying to see someone of Dr Schuchat’s calibre responding to previous claims regarding vaccines in autism I would like to make a few points to Dr Schuchat and the CDC in general.

Firstly, this level of response is around eight years too late. What have you been doing on the media/PR front over the last eight years? I’ll tell you what your ‘opponents’ have been doing – they’ve been conducting protests outside your offices, outside the offices of the AAP etc. They’ve been setting up and organising vaccine/autism groups and heavily marketing them via the use of organic and paid for web based advertising.

The only people who have made any kind of attempt to counter these groups and the misinformation (deliberate or not) they publish is people like myself. I am not attempting to aggrandise myself at all. I am attempting to convey to you how one sided the ‘battle’ has been over the last few years.

Where were you? You were needed. You could’ve helped. Instead you sat back and hoped this would all go away. It didn’t. It won’t.

Secondly, the level of Dr Schuchat’s response is very close to condescending. Simply stating that:

Kirby’s column included many inaccuracies related to childhood vaccines. As such, it illustrates that when it comes to immunizations, child development and specific medical conditions, the best source of guidance is the child’s health care provider.

is patronising in the extreme. The level and quality of the debate has moved on in the last eight years. Bland assurances won’t cut it. You need to be specific and offer evidence. Autistic people, parents of autistic people and interested professionals are smart enough to know and understand a certain level of science these days.

Don’t be shy about providing people with science. You have some truly excellent science on ‘your side’ as I and others have attempted to blog about in the last five years to no small effect. For example, Googling mmr autism displays, amongst others, the blog of a friend of mine – also the parent of an autistic child and also convinced of the need to blog about the bad science surrounding the various vaccine/autism hypotheses. Googling thiomersal autism brings up _this_ blog. We’re doing your job for you!

You’re being left behind in this debate. Its time you caught up.

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