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Social Demographic Change and Autism: part 1

3 Oct

I’ve been meaning to blog this for a long time. Ever since it came online, which was months ago. I’ve wanted to do a good job on this paper and so I’ve kept putting it off while I wait for the time to really dig into it. Kev’s recent post about Prof. Bearman got me thinking it is time to get this out. I knew this would be long and it has grown longer than I expected, so I have split the post up. Here are some introductory thoughts. Much as people like to paint me as being in the “genetics” camp, it isn’t really my interest. Someone like Prometheus would do a far better job on an intro and discussion that I can. But in Prom’s absence, I will say what I can.

Prof. Peter Bearman is a researcher at Columbia University. His team has taken a very careful look at the California Department of Developmental Services (CDDS) data and combined this with California birth record data and come up with what are likely some of the best papers to come from those data. The CDDS provides services to the developmentally disabled in California through a series of “Regional Centers”, which are private corporations which administer the state’s funding through largely non-governmental agencies in the state. They have records on the people (consumers) whom they have served over the years and these data include information on how the consumers qualify for services.

There are five eligibility categories for regional center support:

1) Mental Retardation: Significant deficits in general intellectual functioning (generally an IQ of 70 or below) and significant deficits in adaptive functioning.

2) Cerebral Palsy: A neurological condition occurring from birth or early infancy resulting in an inability to voluntarily control muscular activity, and resulting in significant deficits in motor adaptive functioning and or cognitive abilities.

3) Epilepsy: A disorder of the central nervous system in which the major symptoms are seizures. Eligibility is based on a seizure disorder that is uncontrolled or poorly controlled , despite medical compliance and medical intervention.

4) Autism: A syndrome characterized by impairment in social interaction (withdrawal, failure to engage in interaction with peers or adults), delays in both verbal and nonverbal communication skills, deficits in cognitive skills, and impairment in the ability to engage in make-believe play. Individuals may engage in repetitive activities or a limited repertoire of activities.

5) Fifth Condition: This category includes disabling conditions found to be closely related to mental retardation or requiring treatment similar to that required for individuals with mental retardation.

As a side note, a lot of people forget the “Fifth Condition” category. People will say that people with Asperger Syndrome or PDD-NOS don’t qualify for Regional Center services. Well, they don’t under the “autism” category, but they can under the fifth condition if they meet the requirements for a “substantial disability”. But, I am digressing.

The CDDS data have been extensively used to demonstrate the very large increase in autism prevalence that has occurred over the last 20-30 years.
Prof. Bearman’s group has studied the CDDS data and found that some of the increase can be found to attributed to factors such as changes in the way people are diagnosed (diagnostic accretion) and lower ages of identification.

In a recent paper, Social Demographic Change and Autism, Prof. Bearman’s group argues that about 11% of the rise in autism prevalence can be attributed to genetics.

Sorry to give away the conclusion so early but this is going to be long and I know a lot of people won’t read it all.

Genetics is a hot-button issue with a lot of people in the online autism community. Sometimes people will divide the world into two camps: those who believe autism is caused by vaccines and those who believe autism is caused by genetics. It is a major oversimplification but it happens.

Another oversimplification is to confuse genetics and heritability. As in, “I’m not autistic and my wife isn’t autistic, genetics doesn’t account for my kid being autistic”. This is wrong on so many counts. Heritability implies genetics, but not all genetics is heritable.

In high school or even earlier you probably learned about a monk and pea plants and later studies on fruit flies and the color of their eyes. This is Mendelian inheritance. You learned that some traits are recessive and some are dominant.

From this framework, you can’t get a genetic epidemic.

Whenever the argument about genes and changing prevalence comes up, you can be sure someone will eventually bring up Down Syndrome. Down Syndrome is a developmental disability (possibly an example of the sort that comprise the “fifth category” in the DDS). Down Syndrome is genetic. Not always Mendelian inheritance genetic, but genetic all the same.

The risk factors for having a child with Down Syndrome are

1) Advancing maternal age. A woman’s chances of giving birth to a child with Down syndrome increase with age because older eggs have a greater risk of improper chromosome division. By age 35, a woman’s risk of conceiving a child with Down syndrome is 1 in 400. By age 45, the risk is 1 in 35. However, most children with Down syndrome are actually born to women under age 35 because younger women have far more babies.
2) Having had one child with Down syndrome. Typically, a woman who has one child with Down syndrome has about a 1 percent chance of having another child with Down syndrome.
3) Being carriers of the genetic translocation for Down syndrome. Both men and women can pass the genetic translocation for Down syndrome on to their children.

Part 2 and 3 are what we usually think of as “genetic”, as in “Mendalian”. But what about (1) advancing maternal age? A 10 times greater risk for older mothers? Keep in mind, there is a clear genetic difference behind Down Syndrome.

In humans, the egg cells and sperm cells have 23 chromosomes. The rest of your cells normally contain 23 pairs of chromosomes — one from your father and one from your mother. Kids with Down syndrome usually have three copies of chromosome 21 — called trisomy 21 — instead of two copies.

There is a difference, some might call it an error, in the genetic sequence which leads to Down Syndrome. The parents don’t need to have it. It can be genetic and not heritable. Or, at least, not heritable in the way most people think.

Parental age is increasing. We would be seeing an epidemic of Down Syndrome if it weren’t for the genetic test that is available and offered to most pregnant women.

There are already studies out discussing increased risk for having an autistic child with parental age. If parental age is increasing (and it is), why don’t we see an epidemic of autism from this?

Add to this the recent study from the Autism Genome Project (which came out after this paper by Prof. Bearman’s group). That study, and others, are showing that rather than an autism “gene”, that copy number variations (CNVs) may be one source of genetic risk for autism. These are not heritable in the usual sense as usually they exist in the child and not the parent.

According to Prof. Bearman, we are seeing it. It accounts for about 11% of the increase in autism prevalence in the CDDS data. It is a big effect, but small compared to the other factors going on (the other 89%). So without a careful look, one can’t show it.

Prof. Bearman’s group *is* taking a careful look. The result is their paper Social Demographic Change and Autism. There are a lot of very interesting results, like twin concordance being much smaller than has been previously reported. Another recent paper confirms that. Strangely, no one seems to have noticed.

I’ll try to rectify that in the next installment when we look closer at the paper. Until then, here is the abstract:

Parental age at child’s birth—which has increased for U.S. children in the 1992-2000 birth cohorts—is strongly associated with an increased risk of autism. By turning a social demographic lens on the historical patterning of concordance among twin pairs, we identify a central mechanism for this association: de novo mutations, which are deletions, insertions, and duplications of DNA in the germ cells that are not present in the parents’ DNA. Along the way, we show that a demographic eye on the rising prevalence of autism leads to three major discoveries. First, the estimated heritability of autism has been dramatically overstated. Second, heritability estimates can change over remarkably short periods of time because of increases in germ cell mutations. Third, social demographic change can yield genetic changes that, at the population level, combine to contribute to the increased prevalence of autism

Is the end of the Omnibus Autism Proceeding near?

2 Oct

The Omnibus Autism Proceeding (OAP or omnibus) is the way the Court of Federal Claims (vaccine court) has been handling the now 5,000+ claims submitted for autism as a vaccine injury. The Omnibus started officially in July of 2002 with Autism General Order #1. Along the way it was decided that the best way to handle the large number of claims was using “test cases”. Three test cases were heard for each of two “causation theories”. The idea was that “general causation” arguments could be made once, and very thoroughly, and the other cases could be decided on the outcome.

The first causation theory was that the MMR vaccine in combination with thimerosal could result in autism. The test cases for this theory were those of Michelle Cedillo, William Yates Hazelhurst and Colten Snyder. Attorneys for the families presented evidence for a mechanism where thimerosal was proposed to reduce the immune response and the MMR vaccine led to a persistent measles infection which, again as proposed, led to symptoms of autism. In all three cases the special masters (judges) ruled against the petitioner families. They found that the evidence did not support the mechanism proposed.

The second causation theory held that thimerosal in vaccines could result in autism. Three test cases were presented, again with individual and general causation evidence. The test cases, Jordan King and William Meade, and Colin Dwyer were heard. Their attorneys argued that mercury from the thimerosal in the vaccines accumulated in the brains and resulted in neuroinflammation which, in turn, resulted in autism. As with the MMR case, the special masters ruled against the petitioner families.

To put it simply: all the data and all the experts that could be put together to support the idea that vaccines cause autism weren’t persuasive. They came up with two stories (MMR and thimerosal) and neither story made a case that was even close (the special master’s word).

Some of the petioners appealed. Some appealed to multiple levels. The appeals were denied.

The Court recently issued an update letter. I quote part of it below:

As described above in part I of this Update, all of the court rulings in the six test cases described above have found no causal link between autism and MMR vaccines and/or thimerosal containing vaccines. Further, the PSC has informed the special masters that no additional OAP test cases are contemplated.

Therefore, the Office of Special Masters has begun discussions with members of the petitioners’ bar and respondent’s counsel about how best to conclude the approximately 4,700 autism cases remaining open on the court’s docket. To aid in that process, some petitioners’ counsel have contacted all of their OAP clients to advise them of the results in the test cases and to recommend a course of action with regard to their claims. Additionally, all petitioners who are not represented by counsel have been ordered to inform the court either that they wish to dismiss their claim or that they intend to proceed with their case. For petitioners who wish to continue with their claim, orders to identify a theory of causation, produce an expert report, and file additional evidence will follow. Petitioners’ counsel who have not yet done so are encouraged to contact their clients and determine how their clients wish to proceed.

The issue of attorneys’ fees and costs for petitioners’ counsel is part of the discussion about how to conclude proceedings on the OAP petitions. Mediation efforts are underway to develop methods to resolve the fees and costs issues, and a report on the progress in these talks is expected at the October judicial conference.

The special masters are assuming that no one will go forward with the MMR and thimerosal theories. Since those theories don’t hold up in court, it seems a good assumption.

Petitioners can still go forward as individual cases, as in any non-omnibus case. They will need to submit records and a theory of causation and support that theory in hearing.

The PSC (petitioner’s steering committee, a group of lawyers which has managed the Omnibus from petitioner’s side) has decided that no additional OAP (Omnibus) test cases are planned.

This is very important. They have no other theories to present. They don’t plan to present “too many too soon”. They don’t plan to present a Wakefield-like theory of persistent measles infections leading to “leaky guts”. They don’t plan to present a “mitochondrial autism” theory.

This last bit is very important. The Hannah Poling case made a lot of news when it was leaked that the government had conceded her case as a table-injury MMR encephalopathy. She was supposed to be one of the three thimerosal test cases. At the time of the concession and since, it was asserted that her case was “not rare” and that the attorneys were prepared to go ahead with the mitochondrial disorder story. It would appear that there are not many (if any) other “Hannah Poling” cases out there. There is at least one family pursuing a variation of the mitochondrial disorder theory. Alexander Krakow was scheduled to be a test case for the thimerosal theory and his family pulled out of the Omnibus to pursue the mitochondrial theory.

While there may be a case or two that we hear about from here on out, it appears that the Omnibus, the “class action” type phase, is over.

Incidence of autism in Berkshire

30 Sep

A Reading Borough Council report has shown that the incidence of autism in a borough of Reading, Tilehurst has increased over a period of eight years (2000 – 2008) from 68 to 186, more than doubling.

Lets put these figures in context of a few things. Firstly, thiomersal. Thiomersal was removed from all UK vaccines in 2004. The average age of autism diagnosis is five and a half (PDF) in the UK. This would mean that if thiomersal caused autism, a significant drop off in autism incidence would have been reported to have been occurring during late 2009 early 2010. This was not reported. This could be because the report did not go beyond 2008 but again there’s no mention of that either and I can’t find the relevant document on the Reading Borough Council website

Secondly, the report seems quite clear to refer to diagnoses of ASD which includes PDD-NOS and Aspergers Syndrome. Kate Manton of Berkshire Autism Society says:

People are being diagnosed much earlier now than they were 10 years ago. Children at two and a half are being diagnosed, if the condition is fairly severe.

Thirty years ago [someone] who was disruptive in class but fairly bright would be called naughty.

All good points and ones which mitigate against the obvious simplistic claims that there is some sort of epidemic of autism. There may well be some sort of ‘epidemic’ of _recognition_ of autism in all its many forms but thats not the same thing at all.

I’m left wishing I could get hold of a copy of the same data that the BBC did so to that end I have requested that the BBC send me a copy of the report. Hopefully they’ll reply.

The Age of Autism before thimerosal

28 Sep

Dan Olmsted and Mark Blaxill have written a book, The Age of Autism. It expands on Mr. Olmsted’s UPI series of the same name and uses the same logic: build a narrative that links mercury to illnesses and claim this as proof that mercury is the cause.

One can download the first 46 pages of the book for free on iTunes, buy the book, wait for it to come to your library or used book story (don’t count on the used bookstore route. Last report I got was only about 600 books sold in the opening time for this book). Or, one could just not read it ever.

If you want just an idea of what the book is about you can read a short excerpt on the publisher’s website. It starts with this simple statement:

We believe that autism was newly discovered in the 1930s for the simple reason that it was new.

Why was it new? If I understand the logic, the idea is that a new mercury compound was invented and tested around that time: thimerosal. From a recent interview, here are Dan Olmsted’s words:

What we did really was try to trace the rise of autism and that led us to look at the first eleven families who had children diagnosed in the 1930’s .. in the famous paper. We were able to identify seven of those first eleven kids, who were only known by their first name and last initial. When we did, we found what we thought was significant exposure of the family to mercury, in particular a new kind of mercury that came on the market .. that was used in fungicides for agriculture and in vaccines. So, we think as that happened, the first cases appeared. Then it seemed reasonable to believe that when the vaccine schedule that included much more mercury exploded in the 1990’s and so did autism .. there’s probably a connection that has been missed here.

First eleven kids? First studied or first with autism? They seem to be asserting that these are, indeed, the first autistics ever.


Thimerosal was invented in 1927. What strikes me odd about the position of Mr. Blaxill and Mr. Olmsted is that ten years before the invention of thimerosal, someone was born who would later be diagnosed with autism and receive support from the California Department of Developmental Services (CDDS) under the label “autism”. I know this because the data are publicly available. The CDDS data have been used for years to promote the idea of a vaccine-induced autism epidemic. Of course Mr. Olmsted and Mr. Blaxill are aware of these datasets as their colleague David Kirby made use of them many times over the years in his promotion of autism as vaccine injury, starting with his book “Evidence of Harm, Mercury in Vaccines and the Autism Epidemic: A Medical Controversy.”

Here is a list of the birth year and the number of people for each birth year who were getting services from the CDDS (note that these data were from the 1990’s. Some or all of these autistics may have passed on):

Birth-year number of CDDS consumers under the autism label
1930 1
1929 2
1928 3
1924 1
1923 1
1922 3
1917 1

There were not a lot of autsitics born before 1930 and still alive receiving services in the 1990’s, this is true. But, the oldest person in that group was 78 at the time. That’s one year older than Donald T. is this year, for those following that story. .Be that as it may, there are a number of CDDS consumers who were born before thimerosal was invented. It would be unwise to assume that these are all the people born before 1930 who were diagnosed autistic. They are but an example.

From what I’ve read, Mr. Olmsted and Mr. Blaxill spent about five years looking for the origins of autism (the time since Mr. Olmsted’s original UPI series of articles). They traveled internationally and, from their description at least, appear to have left no stone unturned in their search.

I wonder, did they ever challenge their assumption that autism was new? Did they seek out autistics who predated thimerosal and/or those who weren’t research subjects of Dr. Kanner? Or did they merely rework and expand on Mr. Olmsted’s previous work on Kanner’s subjects?

In their statement attempting to distance themselves from anti-vaccine groups, Mr. Olmsted and Mr. Blaxill state:

We don’t want crops to wither, or houses to rot, or children to die of vaccine- preventable illnesses. We simply want to stop an autism epidemic whose origin we believe can be discerned from a careful examination of its environmental history.

“Careful” examination. I wonder.

Safeminds comments on the latest thimerosal-autism study

21 Sep

SafeMinds is an organization which has long promoted the idea that thimerosal caused an autism epidemic. They may be the single greatest force that got the idea into the public’s eye, and got research funding focused on looking at the question.

SafeMinds has shown themselves to be very resistant to the very research they called for. Studies which show a lack of association between thimerosal containing vaccines (TCV’s) and autism are always rejected by SafeMinds. They are not alone in this, groups such as Generation Rescue and the National Autism Association (NAA) have also refused to accept the science.

So it was with no surprise that I read that SafeMinds had issued a statement against the study. The statement starts by pointing out that the study was funded and performed by those with conflicts–the CDC, Abt (an organization which does contract research for groups including the CDC), and HMO’s “which receive substantial funding from vaccine manufacturers to conduct vaccine licensing research”.

If we can’t use the HMO’s to work on such project, that sort of takes away the VSD as a tool. It certainly takes away the opportunity to do anything more than passive surveillance of the VSD data. One of the strengths of the Price study was the effort to do more than just review the medical charts. They worked with the children, both cases and controls, to verify that the autism counts were accurate. I bring this up because groups like SafeMinds frequently request access to VSD data.

SafeMinds also discusses the study methodology:

The study sample did not allow an examination of an exposed versus an unexposed group, or even a high versus a low exposed group, but rather the study mostly examined the effect of timing of exposure on autism rates.

There is much wrong with the above statement. Let’s start with where they are close to correct. The study sample did not allow for a direct comparison (with good statistics) of exposed vs. unexposed. This is true. This is because there are few unexposed kids (unexposed=no thimerosal exposure in this study. Unexposed does not mean no vaccines). If you look at exhibit 9.1.4 from the technical reports by Abt associates (the detailed reports on the study), you will see about 20-30 “unexposed” children. I.e. children with no thimerosal exposure. Of those, about 3-4 (out of 1,000) had no HiB, HepB or DTP vaccine vaccine at all (MMR isn’t listed as it is not a source of thimerosal). This is in line with estimates by the CDC of how many children are unvaccinated (typically about 0.4%). (as an aside–this points out how difficult it would be to do a good study of vaccinated vs. unvaccinated children using the VSD. Seriously, with 99.6% of kids receiving at least one vaccine, you would need a huge number of kids to get the number of unvaccinated needed for good statistics).

Here is that exhibit, with the no-exposure kids circled. (click to enlarge)

It would appear to this reader that the issue of unexposed vs. exposed isn’t so much one of “study design” as the limitations of the VSD itself. There just aren’t that many autistic kids to make a good statistical comparison of unexposed vs. exposed populations.

And, it should be noted, an unexposed vs. exposed comparison wasn’t the purpose of this study. One big question posed by SafeMinds and later picked up by groups such as Generation Rescue was simple: did the increase in thimerosal exposure from vaccines in the 1990’s result in an “epidemic” of autism? This is the question this study addressed.

I am at a loss as to why SafeMinds wrote this: “….or even a high versus a low exposed group, but rather the study mostly examined the effect of timing of exposure on autism rates”. Contrary to SafeMinds’ assertion, there is a large variation on thimerosal exposure in the study subjects. One of the surprising facts from this study was the number of children receiving thimerosal-free vaccines. This, together with variations in the number of vaccines administered, led to a much larger distribution in thimerosal exposures than one would expect based on the vaccine schedule alone.

Thus, the study was not on “timing” at all. It was, as advertised, on variation of exposure of thimerosal. The question is (at least to me), does the range of exposure amount to significant number of kids having “low” levels of exposure by SafeMinds’ definition?

The answer, it turns out, is yes.

Safeminds has the following statement on their website:

[Autism] remained rare (1 in 10,000) until the rapid escalation of vaccines beginning in the late 1980’s (from 10 shots of 7 antigens in 1983 to 36 shots of 15 antigens). Vaccines are a likely candidate to explain some, if not most of the rise in autism cases and possibly other chronic childhood disorders linked to immune system malfunction.

In one of the seminal papers on the thimerosal was co-written by SafeMinds founder Lyn Redwood Autism: a novel form of mercury
poisoning. In it, the authors state:

The discovery and rise in prevalence of ASD mirrors the introduction and spread of TMS in vaccines. Autism was first described in 1943 among children born in the 1930s (123). Thimerosal was first introduced into vaccines in the 1930s (7). In studies conducted prior to 1970, autism prevalence was estimated, at 1 in 2000; in studies from 1970 to 1990 it averaged 1 in 1000 (124). This was a period of increased vaccination rates of the TMS containing DPT vaccines among children in the developed world. In the early 1990s, the prevalence of autism was found to be 1 in 500 (125), and in 2000 the CDC found 1 in 150 children affected in one community, which was consistent with reports from other areas in the country (126). In the late 1980s and early 1990s, two new TMS vaccines, the HIB and Hepatitis B, were added to the recommended schedule (7).

I know I am spending a lot of time on this point, but it is important. The idea that there is a dose-response relationship between thimerosal and the presumed risk of autism is fundamental to the arguments made by groups like SafeMinds.

A sister organization to SafeMinds, Generation Rescue, says the same thing. In their take, “This is the schedule from 1983. If it worked for kids then, why doesn’t it work for kids now?”. Generation Rescue leader and spokesperson Jenny McCarthy wrote in her book, Healing and Preventing Autism: A Complete Guide, “In 1983, we had 10 shots on the vaccine schedule and autism was one in 10,000. Today there are 36 given and autism is nearing one in 100”. I.e. if we go back to the 1983 vaccine schedule, autism rates should drop to 1 in 10,000.

The 1983 schedule, as graphically presented in expensive full page newspaper ads by Generation Rescue, included 4 DPT shots (yes, the old whole cell pertussis vaccine). Each of those shots included 25 micrograms of mercury.

It strikes this reader that the thimerosal exposure from 4 DPT shots, the amount in the 1983 schedule that supposedly only resulted in 1 in 10,000 kids having autism, should be a “low” exposure amount. If groups are going to point to 1983 as a safer schedule and point to the increases in thimerosal exposure in the 1990’s as the major sign of the “epidemic”, we should be able to take their word that the levels in 1983 were somehow safer.

Let’s look at that figure from the Price study again, shall we? I will highlight how many kids have “low exposure” (i.e. comparable to the 1983 vaccine schedule) to thimerosal. Again, click to enlarge if you wish.

By my eye, something approaching 50% of the kids in the study received the thimerosal exposure of the 1983 schedule. Certainly more than 25%. Those highlighted in red have the same thimerosal exposure as kids did in 1983, so they should have the same autism prevalence that SafeMinds and Generation Rescue claim for that time period: 1 in 10,000.

If that group has a prevalence of 1 in 10,000–or even anything significantly lower than the prevalence of those with higher thimerosal exposure– this study would have found it.

In other words, a thimerosal-induced epidemic of autism didn’t happen. Even using the logic that SafeMinds used to hypothesize it in the first place:that, somehow, the thimerosal exposures in 1983 resulted in a low autism prevalence.

Yes, this is far from rigorous. But, so is the logic that claims that increased thimerosal exposure led to an autism epidemic.

If we read further into the SafeMinds response, we see some of the confusion:

The study sample did not allow an examination of an exposed versus an unexposed group, or even a high versus a low exposed group, but rather the study mostly examined the effect of timing of exposure on autism rates. There were virtually no subjects who were unvaccinated and few who were truly less vaccinated; rather, the low exposed group was mostly just late relative to the higher exposed group, ie, those vaccinating on time.

SafeMinds seems to be assuming this is a study on the number of vaccines, not the amount of thimerosal. They also don’t appear to have read the study thoroughly enough to note that, yes, there is a large fraction who were “less vaccinated” and, more importantly to this study, a large fraction who had lower thimerosal exposures. As noted above, the low thimerosal exposures result from the fact that many of the children received thimerosal free vaccines.

It is unfortunate that SafeMinds (and other groups like them) can not adapt to science as it comes out. Science which clearly shows that many of their hypotheses were wrong.

The Respectful Insolence blog also discusses some of the failings of the SafeMinds response.

New thimerosal/autism paper – signal vs noise

13 Sep

The new thiomersal paper that Sully has blogged will be attacked by the antivaxxers in at least one key area. The area that will be attacked is – to those well schooled in the way good science operates – a standard way to improve the signal to noise ratio of the results. Or to put it another way, ensures ‘cleaner’ results.

From the paper:

…Children were excluded if they had the following medical conditions with known links to ASD traits: fragile X syndrome; tuberous sclerosis; Rett syndrome; congenital rubella syndrome; or Angelman syndrome…

So first of all why were children that fell within these groups excluded? As I said, the answer is to ensure better data. In order to get a cleaner signal, the more noise that can be eradicated the better.

In this instance, children who already have existing medical conditions known to be related to autism would produce noise. We already know what caused their autistic traits hence establishing a clear link to thiomersal would not be possible. In a very meaningful way, doing this does a large favour for antivax group. If these children were eradicated from the study and a clear link to thiomersal _had_ been established then denying the link would be very much more difficult.

However don’t expect the antivaxxers to see this. Or even if they _do_ see it, they will look away purposefully. They will use the fact that these children were excluded and say _”See? ‘They’ have to hide the autistic children!”_ .

When you see this tactic – and you will see it – see it for what it is. It’s simple noise generation to obscure the clear signal coming through. Thimerosal in vaccines doesn’t cause autism. And it never did.

The autism ‘epidemic’ no more

17 Aug

OK, so its well known to LBRB readers that I don’t think its ever been scientifically established that there has been such a thing as an autism epidemic but even so, looking at why autism numbers have changed over a certain period of time – the period of time people believe is part of the ‘epidemic’ – should be a good way to determine what contributed to that time periods rise in autism.

So thats what Peter Bearman did. Summed up well in this weeks New Scientist, Bearman’s study offers the first look at what actually did cause the ‘epidemic’.

Better diagnosis
Diagnostic changes are the most important influence. After 1987, the definition of autism used in California was broadened several times. Bearman and his colleague Marissa King examined the medical records of around 7000 Californian children with autism and found that one in ten had initially been diagnosed with mental retardation. Extrapolated to the state as a whole, they estimate that this change in diagnosis created almost 5000 extra cases of autism between 1993 and 2005, or 26 per cent of the increase of recorded over that period.

Greater awareness
Social influence accounts for another big chunk of the overall increase. Parents are more aware of the disorder than they used to be, and so those whose children who have mild forms of autism have become more likely to seek out diagnosis.

Bearman and his colleague Ka-Yuet Liu quantified this effect. They first estimated how the chances of a child being diagnosed with autism increase if he or she lives close to a child that has already been diagnosed. They then plotted the addresses of children with and without autism in California to calculate the number of children who had grown up close to a child diagnosed with the condition. They were then able to calculate the fraction of extra cases that would have been diagnosed as a result of social interactions. They put this figure at 16 per cent.

Older parents
The final contribution to the rise in diagnoses comes from demographics. Couples in California are having children later in life, as they are in much of the rest of North America and Europe. That is pushing up autism rates, because autism is triggered by genetic mutations that older parents are more likely to pass on to their children.

Bearman and King calculated that these older parents are responsible for 11 per cent of the extra autism cases.

So these total 53% of the so-called ‘epidemic’. What about the missing 47%? Well, Professor Roy Grinker says:

Autism used to be highly stigmatised, in part because it was thought to be due to poor parenting. The removal of that stigma has made doctors and parents more willing to recognise the disease, which will have contributed to [some of] the extra cases…This and other social causes, together with uncertainty in the number of cases that can be attributed to the factors already studied by Bearman, could account for much or all of the unexplained half

But note Grinker doesn’t say it definitely does. This is because he knows as a careful scientist it hasn’t been looked at.

So what can we take from Bearman’s work? In my opinion we can take the fact that as soon as the questions regarding non-environmental causes were actually looked at and studied, there were numerical values that could be applied to their contribution. There are other non-environmental causes which Bearman didn’t look at which would probably be found to contribute to the other half.

What about the alleged environmental causes? It would not surprise me in the least if it were found that there were some. But as to what they are, the environmental lobby are still so hung up on vaccines they don’t seem to want to look at other possible environmental issues. Maybe its time they dropped the vaccine nonsense and got involved in some decent research. Just a thought.

Prof. DeSoto discusses mercury and autism

3 Aug

A recent issue of the journal Acta Neurobiologiae Experimentalis (ANE) focused upon autism. Not just autism, but autism causation with papers on vaccines, acetaminophen and, of course, mercury. The idea for this focus edition came from Professor Dorota Majewska who holds the EU Marie Curie Chair at the Institute of Psychiatry and Neurology in Warsaw, Poland. The authors for this focus issue are largely the same as those from a conference Prof. Majewska organized in 2008, Autism and Vaccinations.

One of the papers in the focus edition of ANE was the paper by Hewitson et al., that we have discussed at length here at LeftBrainRightBrain.

Another paper in this focus edition is Sorting out the spinning of autism: heavy metals and the question of incidence by M.C. DeSoto and R.T. Hitlan. DeSoto and Hitlan gathered some attention for a paper a few years back where they analyzed an existing data-set, that by Ip et al.. D’oC and Interverbal discussed this paper at the blog Autism Street, starting with A Tale Of Two Tails. In that piece, D’oC and Interverbal discuss the statistical analysis used by DeSoto and Hitlan. Prometheus at the Photon in the Darkness blog also discussed the DeSoto and Hitlan paper in Winter Potpourri. Pure Pedantry blog at ScienceBlogs also discussed this study in Mercury, Autism, and a Note on Scientific Honesty. Perhaps the best analysis of the original DeSoto and Hitlan paper was performed by EpiWonk, an epidemiologist.

The recent paper by DeSoto and Hitlan, Sorting out the spinning of autism: heavy metals and the question of incidence, is basically a review article. It has been touted as support for the mercury hypothesis with a commonly quoted phrase,

Fifteen were offered as evidence against a link between exposure to these metals and autism. In contrast, a sum of 43 papers were supporting a link between autism and exposure to those metals

I somehow doubt the authors intended the debate to boil down to counting papers. It would be a weak support, and rather ironic at that as this paper is placed in exactly the sort of journal that leads to large numbers of papers supporting the heavy-metal/autism link. The current DeSoto and Hitlan paper is in a focus issue on autism in ANE which selected papers which support autism as vaccine injury. Many papers on the mercury appear in lower impact journals and by authors such as the father-son team of Geier and Geier (which if I counted correctly account for 19 of the 43 articles on DeSoto and Hitlan’s list). If you are unfamiliar with that team, the neurodiveristy.com blog has many articles on the team such as Significant Misrepresentations: Mark Geier, David Geier & the Evolution of the Lupron Protocol (Contents).

That said, I was planning to avoid the recent DeSoto and Hitlan paper. It isn’t really new (adding to the number of articles on toxins and autism without adding to the knowledge base). I was going to avoid the paper, that is, until Prof. DeSoto gave an interview for the Age of Auitsm blog. I don’t understand why the Age of Autism considers Prof. DeSoto to be an expert on so many areas of autism and the environment. The breadth of her work is not great. Below is an exchange which shows what I mean. Prof. DeSoto was asked to comment on the recent study by Hewitson et al., comparing vaccinated and unvaccinated monkeys.

Q: There is a study published in Acta Neurobiologiae Experimentalis alongside yours that deals with vaccinated and unvaccinated primates. Do you have a reaction to the study or its conclusions?

Dr. DeSoto: All the primates were vaccinated, the difference was whether there was a heavy metal additive. This is a potentially important study. There are a few weaknesses that prevent strong conclusions. The size of the control group is small (apparently n=2). Given that rhesus neural development within the brain region of interest is not all that well documented, a larger control group would have been desirable. This weakness is acknowledged by the authors.

Isolating the infant monkeys shortly after birth is a significant change from normal environment. The severing of the maternal bond and being raised essentially alone (only visual contact was maintained with the peer infants) affects every aspect of development – including neural development. There is evidence that brain volume is specifically affected by isolation. The rearing situation in the study, in my mind, is not very comparable to normal development, especially if the outcome of interest includes brain volume.

That said, this is the only study that has compared the net effect of multiple vaccination additives on brain development. Above all, I have to editorialize and say this seems difficult to understand (that is – why is this the only study?). If some scientists and some parents question the safety of the vaccine schedule, such studies as this one are the way to investigate the concerns.

Now, the one study that exists (even if there are caveats that go with pilot research) suggests there are differences. Whether one is of the opinion that individually testing vaccines is as good as testing the combined effect or not – at this point it is imperative that additional studies be conducted on the additive effect of the full vaccine schedules.

To be clear and to repeat, if one thinks that the vaccines with additives given in close succession have no effect on neural development– this ought to be established empirically. One thing that I noticed in the study is the main effect for difference in brain volume (no time effect). It should be noted that this suggests the early administration of additive-containing vaccine (first four rounds) was a culprit of interest.

Prof. DeSoto did not take a careful look at the Hewitson et al. study. How do I know this? In the above interview, DeSoto states:

“All the primates were vaccinated, the difference was whether there was a heavy metal additive”

The paper states, “”Four infants were assigned to the unexposed study group and received saline injections according to the schedule in Table I””. The differences included the heavy metal additive, as well as all the ingredients that make a vaccine differ from saline.

What amazes me is that the interviewer at the Age of Autism missed that as well. Even though AoA has touted the Hewitson study greatly, they don’t appear to have read it closely.

This is not a minor detail. It is key to the study design and conclusions.

Another comment:

Given that rhesus neural development within the brain region of interest is not all that well documented

I think that Prof. DeSoto can be excused for not realizing that there is a study tracking the development of precisely the amygdala in macaques. This is because Hewitson et al. did not include that reference (which was easily found in a pubmed search).

“The size of the control group is small (apparently n=2)”

The control group was 4. One was excluded for “scheduling reasons” and the other for unknown reasons. This was a major problem with the study. Fatal, one might say, as the brain sizes of the control group didn’t grow between the two time periods tested (about 4 months and about 6 months of age) for the monkeys. At the same time, their amygdalas shrank. This was a big warning sign that something was amiss with the control subjects, but this was ingored by Hewitson, et al.. Based on this faulty premise, Hewitson et al. claimed that the brains and amygdalas of the vaccinated monkeys were on an abnormal growth path. It is amazing that Prof. DeSoto missed that.

A fact that I am not surprised that Prof. DeSoto missed is that in a previous IMFAR abstract on this group, Hewitson et al. came to the exact opposite conclusion: that the brains of the vaccinated monkeys did not grow as fast as the unvaccinated monkeys.

Back to the recent DeSoto and Hitlan paper. They make the following statement:

It is worth noting that there have been only three empirical articles directly comparing those with and without an ASD on mercury levels in the body to a control group of normally developing matched controls that report that report no link (Ip et al. 2004, Soden et al. 2007, Hertz-Piciotto et al. 2010). While, the most recent article appears to be the strongest, lacking any obvious errors or flaws (we think that this recent article does provide at least some legitimate evidence contradicting the hypothesis that autism and heavy metals are linked), the other two are seriously flawed.

In the end, this mention of the Hertz-Picciotto study is why I decided to write about the DeSoto piece, and in the process bring in the interview.

Part of what made the Hertz-Picciotto study strong was the fact that they controlled for fish consumption. Correct me if I am wrong, but I believe this is something that Ip did not do, nor did DeSoto and Hitlan in their re-analysis. I don’t see mention of fish consumption in the recent DeSoto and Hitlan paper.

Again, I’ll point out that the analysis by EpiWonk was thorough and clear. I wish he had published it. I don’t think consider fish consumption to state that the DeSoto/Hitlan re-analysis of the Ip data is likely not thorough enough to make the conclusions they draw.

The fact of the matter is, the Ip data just aren’t that profound. It was worthwhile to do a re-analysis given the errors in the Ip dataset and paper. But it was three years ago that DeSoto and Hitlan did their re-analysis. In the meantime, Hertz-Picciotto et al. have a better dataset and a more thorough analysis.

DeSoto and Hitlan editorialize a bit in their paper:

If a person has publicly staked his/her career on a certain position being right, it may become harder to keep a truly open mind, even when new data become available and even when the original intent was to be objective. A way this bias might manifest itself is an overstatement or slight misstatement of results. We feel that both sides have been guilty of this, and this happens when a person becomes so confident in the correctness of his/her own view that he/she no longer reviews evidence to the contrary. Unconscious bias may exist even in the best scientists.

This begs the question of whether DeSoto and Hitlan are as guilty of those they chide. Re-analyzing the Ip data is not staking their career on a certain position. Repeatedly publishing on such a limited dataset does make this reader start to question whether some piece of their reputation is now tied to this position. With apologies to Prof. DeSoto, but the fact that her misimpressions of the Hewitson et al. paper are skewed towards the mercury hypothesis makes me wonder even more.

The autism research community needs to have fresh eyes looking at questions and data. DeSoto and Hitlan did well to reanalyze the Ip data once the mistakes were shown. They just appear to this observer to have (a) overstated the interpretation of their analysis and (b) gotten very quickly in to exactly the sort of rut they accuse others of being in.

Prevalence Rates of Autism Spectrum Disorders Among the Old Order Amish

17 May

One of the topics that comes up over and over online is “The Amish don’t vaccinate” and “the Amish don’t have autism”. Both statements are incorrect. The Amish have no religious prohibition against vaccination and they do have autism.

The question of autism amongst the Amish has been studied and is being presented at the IMFAR autism conference this week. The paper,
Prevalence Rates of Autism Spectrum Disorders Among the Old Order Amish, demonstrates a preliminary prevalence of 1 in 271 as the prevalence of autism amongst Amish children in two Amish communities: Holmes County, Ohio and Elkhart-Lagrange County, Indiana.

J. L. Robinson , Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL
L. Nations , Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL
N. Suslowitz , Center for Human Genetics Research, Vanderbilt University, Nashville, TN
M. L. Cuccaro , Human Genetics, University of Miami School of Medicine, Miami, FL
J. Haines , Center for Human Genetics Research, Vanderbilt University, Nashville, TN
M. Pericak-Vance , Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL
Background:

The prevalence rate of Autism Spectrum Disorders (ASD) appears to be steadily increasing. The latest report from the Center for Disease Control estimates the rate of ASD is 1 in 91 children (Kogan, 2009), up from 1 in 150 in 2007. Understanding the seeming changes in ASD prevalence require careful exploration of genetic and environmental factors. A method that has proven useful in dissecting the etiology of complex diseases is the study of isolated populations. One population isolate that has been studied extensively is the Amish, with well over 250 genetic studies. Expanding studies of autism to the Amish may provide important information about etiology. A crucial first step in this process is a feasibility study to determine ASD prevalence rates in this population.

Objectives:

This study presents preliminary data on the estimated prevalence of ASD among the Amish in two Amish dominant counties as part of a larger epidemiological study. All children between ages 3 to 21 in those counties will be screened for the presence of an ASD.

Methods:

Screening occurred in, two of the largest Amish communities in the United States. Trained clinicians ascertained door to door using a published Amish Directory as a guide. Families were approached and asked to participate in a brief interview regarding their children. Two primary screening instruments were used: the Social Communication Questionnaire (SCQ) and the DSM-IV-TR Checklist (a tool created by the authors). A Vaccination History and a brief family history including questions specific to the ASD phenotype were also taken. Children screening positive on either the SCQ or DSM-IV-TR Checklist were seen for a more comprehensive clinical evaluation by two licensed psychologists. This evaluation included the Autism Diagnostic Observational Schedule (ADOS) and Autism Diagnostic Interview (ADI).

Results:

From September 2008 to October 2009, 1899 Amish children were screened in the two Amish communities. A total of 25 children screened positive for ASD on either the SCQ or the DSM-IV-TR checklist. A total of 14 screened positive for ASD on both screeners. Of those 25 children, 14 were evaluated and seven children were confirmed as having a diagnosis of ASD using the ADI and/or ADOS, and clinical judgment. Interestingly, four of the seven only met ASD criteria on the ADOS but not the ADI. Three of the four who were not diagnosed by the ADI only missed criteria on the Behavioral Domain, which may be attributable to the reporting style of Amish caregivers.

Conclusions:

Preliminary data have identified the presence of ASD in the Amish community at a rate of approximately 1 in 271 children using standard ASD screening and diagnostic tools although some modifications may be in order. Further studies are underway to address the cultural norms and customs that may be playing a role in the reporting style of caregivers, as observed by the ADI. Accurate determination of the ASD phenotype in the Amish is a first step in the design of genetic studies of ASD in this population.

Review of Frontline’s The Vaccine War

29 Apr

The Vaccine War has aired. Judging by the responses, one might consider it a success. Pro vaccine groups like Every Child By Two were telling people to watch it. The Autism Science Foundation “highly recommends” watching it. On the other side, the organizations represented by the Age of Autism blog (Generation Rescue, the National Autism Association, SafeMinds, the Autism Research Institute and TACA) are very upset. Jenny McCarthy has gone to the Huffington Post with her side of the story, as has Dr. Jay Gordon, whose entire interview was cut from the program.


An unofficial (and incomplete) transcript is here.

That all said, I both appreciated the program and had my fears realized. In this case, my fears were that people would be given a platform to spread misinformation. And it happened. Jenny McCarthy and others made statements that were, in my view, misinformation. But, I appreciated the fact that Frontline took the time to counter much of the misinformation with actual experts discussing real science.

Frontline describes the show as:

In The Vaccine War, FRONTLINE lays bare the science of vaccine safety and examines the increasingly bitter debate between the public health establishment and a formidable populist coalition of parents, celebrities, politicians and activists who are armed with the latest social media tools — including Facebook, YouTube and Twitter — and are determined to resist pressure from the medical and public health establishments to vaccinate, despite established scientific consensus about vaccine safety.

I think the show accomplished this. There was some cost in terms of allowing Generation Rescue’s misinformation message in TV once again. But, this time, this time they are the problem.

If you watch the introductory 2 minutes of this video, you will get some idea of how the show is presented

Parents, both pro vaccine and not, activists, public health workers and researchers like Dr. Offit telling various sides of the story, with the narrator tying it together.

Narrator: Tonight on Frontline: They’re hailed as medicine’s greatest triumph: conquering smallpox, diphtheria, polio and more. But today, some Americans question if all those vaccines are worth the risk.

The show is in four segments. The titles for these segments should, again, give you an idea of the tone of the show.

1. A visit to Ashland, Oregon. In some American communities like this one, parents are hesitating to vaccinate their children, despite their doctor’s advice.

2. Eroding faith in vaccines. Skeptics target Paul Offit, inventor of the rotavirus vaccine. And many parents are wary of vaccines because they no longer see the diseases.

3. Fearing vaccine risks, especially autism.. Vaccine skeptics like celebrity Jenny McCarthy have organized a community of parents concerned about a vaccine-autism link.

4. The science that launched the movement. A British doctors ’98 study theorized that the measles vaccine causes autism. Soon vaccine critics began questioning other additives in vaccines.

5. What epidemiological studies reveal. No link is found between autism and the MMR shot or thimerosal. And the British doctor’s ’98 study is discredited, but critics demand more studies.

6. Vaccines, what’s at stake. The debate goes beyond the medical risks-benefits: it involves parents’ rights to make choices v. the needs of the community.

In the first segment, they interview a pro-vaccine mother in Ashland. She notes that if there is an outbreak, the response may get contentious. It may get ugly.

Beyond the direct human cost, one of my worries: how much blowback will there be to the autism communities? How much blame will be applied and what will it cost?

As part of the introduction, The Vaccine War discusses the story of Desiree Jennings. She was a Washington Redskins cheerleader who claimed dystonia as an adverse reaction to her vaccine. Her story broke out not through the TV news show that covered her story, but through YouTube. Jenny McCarthy is quoted about how Generation Rescue took Ms. Jennings to see Dr. Rashid Buttar and how chelation and HBOT cured her.

What makes the Desiree Jennings story even more interesting is the possibility that the vaccine-injury/dystonia story may not be real. As noted on LeftBrainRightBrain, Ms. Jennings was later followed by cameras from a TV program and shown to be driving and walking normally.

The possibility that Generation Rescue is using the story even though it may not be true was probed by Frontline. Here is a part of an interview from Frontline with one of Generation Rescue’s founders:

[Frontline]Talk about the viral spread of an image over the Internet, like [Redskins cheerleader] Desiree Jennings’ flu shot story, for example.

It’s remarkably powerful what an image or an idea can do in today’s day and age, and for a group of parents who feel completely outmatched — because think for a moment about who our enemy is; our enemies are the largest pharmaceutical companies on the planet, making billions of dollars in net profit a year — you’d think that we could never compete with that. But an idea can transmit itself powerfully and very cheaply for millions to see.

So in the case of Desiree, here you have an image of this beautiful woman who’s been severely disabled that literally tens of millions of people view overnight, and imagine the chilling effect that has on a flu vaccine that she attributes as the cause of her condition. It’s remarkably powerful.

[Frontline] Does it matter whether it’s true or not?

Truth always bears out in the end, so I’m a firm believer in that. Are there moments in time where truth is exaggerated or expanded? Absolutely. But truth bears out in the end. …

Perhaps I missed it, but it appears to this reader that Frontline’s question was completely dodged. Does it matter whether the Desiree Jennings story is true or not? I think so. But what seems important to Generation Rescue is not the truth of the story, but the fact that it is a gripping narrative that sells their message.

The Vaccine War has a rather large cast, if I may call them that. Parents both pro and anti vaccine, a writer from Ashland who is anti-vaccine, Paul Offit, bioethicist (and polio survivor) Arthur Caplan, Jenny McCarthy, Anthony S. Fauci (immunologist from NIAID), Cynthia Cristofani (pediatric intensivist), Alvaro and Myrian Fontan (a family who almost lost their daughter to whooping cough) and J.B. Handley, Barbara Loe Fisher–plus more.

In some ways, “The Vaccine War” takes the same approach that Dr. Offit uses in books like “Autism’s False Prophets”. Let the skeptics make their points, ask their questions, then respond. Sometimes this is quite jarring.It is tough to sit back and listen to someone spread information and wait for the response.

The Vaccine War is well researched. Even though people like Jenny McCarthy got some air time for their ideas, they are quite upset about the Frontline episode.

Perhaps I am the only one who will find this ironic. In response to this episode, one which discusses how groups like Generation Rescue use social networking on the internet to get their message out, they are taking to social networking. Twitter, blogging…

As noted above Jenny McCarthy and Dr. Jay Gordon have taken to the Huffington Post to respond to the show. the Age of Autism is being very critical. They are attempting to “poll mob” the Frontline website. (humorous aside–they haven’t figured out that the survey doesn’t record their answers. It only shows you how your responses compare to the actual survey.)

If you have friends, family who are wondering about the vaccine/autism “controversy”, this is a good show to refer them to. It gives both sides. It allows people like Jenny McCarthy to give her viewpoint–and it gives the response.

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