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Thrown under the bus…but for a good cause, right?

21 Apr

America is a wonderful place. Where else can someone publish absolute garbage, refuse to retract it, accuse the government of being involved in a massive conspiracy–and still end up on a government committee?

I am speaking of Lyn Redwood. She is one of the coauthors on ‘Autism: a novel form of mercury poisoning’. This was ‘published’ in Medical Hypotheses. I put ‘published’ in quotes because Medical Hypotheses is a pay-to-publish pseudo-journal that has no review (peer or otherwise) at all. OK, the editor does check that the authors are talking about something medical, and makes sure that some sort of narrative is put together. But, scientifically? No review. Too many people, especially those parents with new autism diagnoses for their children, are unaware that “Medical Hypotheses” ‘papers’ have no place next to actual research papers.

If that piece of junk science wasn’t enough, Ms. Redwood was also a co-author on another less-than-worthless Medical Hypotheses ‘paper’, Thimerosal and autism? A plausible hypothesis that should not be dismissed. The first author on that “paper” was Mark Blaxill. Truly, one of the scary moments in the Omnibus proceeding came when the research head of ARI (Autism Research Institute) referred to Mark Blaxill as “brilliant”. No exaggeration–that was a frightening thought to this listener. Mr. Blaxill is probably rather bright and likely good at whatever he does professionally. But the idea that the information is traveling from him to the research head of the Autism Research Institute rather than the other way around is just scary.

The time to pay-to-publish retractions of these papers was years ago. Yet, both papers are still out there, and new parents usually won’t find out for a long time that those papers a junk.

Besides promoting bad science, what do Ms. Redwood and Mr. Blaxill have in common? Well, the Interagency Autism Coordinating Committee, for one thing.

Ms. Redwood sits on the Interagency Autism Coordinating Committee. This group helps coordinate the US Government’s research efforts on autism. Rather that fight for better understanding and services for, say, adults, the poor, or minorities with autism, Ms. Redwood filled meeting after meeting (after meeting) with struggles to get the wording of the Strategic Plan as close as possible to a government admission that vaccines cause autism.

Mark Blaxill sits on one of the working groups for the IACC, probably placed there by Ms. Redwood. Mr. Blaxill, also a co-author on a number of papers that any reasonable person would have retracted by now, has wasted considerable meeting time with long, insulting ramblings. I know there are people who appreciated Mr. Blaxill’s speeches, but I consider likening the other people on the committee to holocaust denialists insulting. Maybe I misinterpreted his repeated use of the phrase “Epidemic Denialists”. If so, I bet I’m not the only one. Somehow, I don’t think I’m wrong. It appears to be an insulting and deliberate choice of phrases.

Unfortunately for the undercounted communities like adults with autism, the poor with autism, minorities with autism–a number of our own–they present an “inconvenient truth” to people like Mark Blaxill and Lyn Redwood. They demonstrate that the numbers groups like SafeMinds use to promote the faux autism epidemic are terribly flawed. If we are still under counting people with autism in the U.S., how can we use the counts from the California Regional Centers or from education data so far as “evidence” of an “epidemic”?

I know I wrote about this issue recently. But, reading the expert report by Dr. Rodier, and writing about it, I realized anew that a few individuals have caused this harm. And, those few individuals could (and should) work hard to correct that harm.

So, in place of calling on the IACC to fund research that could help the under counted, Ms. Redwood and Mr. Blaxill got this paragraph:

Research on environmental risk factors is also underway. An Institute of Medicine workshop held in 2007 summarized what is known and what is needed in this field (Institute of Medicine of the National Academies, 2007). Numerous epidemiological studies have found no relationship between ASD and vaccines containing the mercury based preservative, thimerosal (Immunization Safety Review Committee, 2004). These data, as well as subsequent research, indicate that the link between autism and vaccines is unsupported by the research literature. Some do not agree and remain concerned that ASD is linked or caused by vaccination through exposure to Measles Mumps Rubella (MMR), imposing challenges to a weakened immune system, or possibly due to mitochondrial disorder. Public comment to the Committee reflected opposing views on vaccines as a potential environmental cause. Those who are convinced by current data that vaccines do not play a causal role in autism argue against using a large proportion of limited autism research funding toward vaccine studies when many other scientific avenues remain to be explored. At the same time, those who believe that prior studies of the possible role of vaccines in ASD have been insufficient argue that investigation of a possible vaccine/ASD link should be a high priority for research (e.g., a large-scale study comparing vaccinated and unvaccinated groups). A third view urges shifting focus away from vaccines and onto much-needed attention toward the development of effective treatments, services and supports for those with ASD.

Let’s just pull that last sentence out for emphasis, shall we?

A third view urges shifting focus away from vaccines and onto much-needed attention toward the development of effective treatments, services and supports for those with ASD.

It’s odd to me–I would have fought that language if I were Lyn Redwood. I would have pointed out that I have a broader perspective than just vaccines, and that I also care about development of effective treatments, services and supports. Isn’t it just a little sad that the people who are pushing the vaccine connection don’t have the view that effective treatments, services and supports for those with ASD’s are a top priority?

But, it wasn’t their top priority. It still isn’t. In the end, Lyn Redwood and Mark Blaxill, people who are on the IACC to represent the interests of the entire stakeholder community, threw the underrepresented autistic communities under the bus.

Omnibus Expert: Patricia Rodier

10 Apr

Autism just plain isn’t mercury poisoning. When can we move on?

Even some of the people who loudly promoted the mistaken idea that “autism is just a misdiagnosis for mercury poisoning” have backed off. But, the groups that promote autism as vaccine injury are packrats: once they’ve collected an idea, bad or not, they won’t ever let it completely go.

Some of you will be thinking, dang, another mercury post. I agree, there are a lot of good arguments against blogging about the mercury-autism connection any more. For one, it gives the idea press that it just doesn’t deserve.

I do think this is worth posting about, though. “This” is the expert report from Dr. Patricia Rodier, submitted to the Autism Omnibus Proceeding. In a single document, we now have an expert on both mercury toxicology and autism. Not faux experts, or worse, businesspeople and public relations people, but an actual, bone fide expert in both fields. I.e. we have a good document to give to people who are being snowed under by the misinformation campaign promoting autism as mercury poisoning.

When Patricia Rodier testified in the Autism Omnibus Proceeding, I was very impressed–and I blogged it right away. I remember at the time telling a friend that it was good to finally see someone officially debunking things like Sally Bernard et al.’s paper, Autism: a novel form of mercury poisoning. My friend pointed out that any college freshman in science (and most not in science) should be able to tear that “paper” apart.

Unfortunately, “should be able to tear the paper apart” isn’t enough. Many people don’t have the time and/or energy. So, many people still think that paper is valid. Let’s face it, that “paper” should have been retracted by the authors long ago, but they still soldier on with the “autism is mercury poisoning” message.

Dr. Rodier’s qualifications are quite good. Her summary is quite good:

As a research scientist who has studied both the toxic effects of methylmercury in animals and autism in children and animal models, I believe I am qualified to evaluate the scientific merit of the allegation.

She may be the only person in the world who has studied both mercury toxicity and autism.

What does she think? In a nutshell:

My conclusion is that the allegation has no scientific support and is highly improbable

Dr. Rodier notes that the comparison that autism and mercury poisoning appear similar isn’t even close.

In othcr words, because the symptoms of methylmercury poisoning
are not similar to those of autism, the authors have tried to construct a new, hypothetical kind of mercury poisoning from symptoms of toxicity of other mercury species and symptoms never reported for any kind of mercury exposure. The hypothesis is not based of facts; instead, the facts are being selected, manipulated, and shaped to fit the hypothesis. The hypothesis is then offered as evidence. But hypotheses are not evidence.

Ouch. Ouch, that is, if you are someone promoting autism-as-mercury-posinong.

Dr. Rodier can back up her words, as we discussed in the previous blog post. But, let’s say that again, Dr. Rodier uses research based facts, not manipulated hypotheses, to come to her conclusion.

I need to get a clean copy of that document, one that looks as good as the information it contains. That document needs to get into the hands of people being lured by the pseudo scientists promoting autism as mercury poisoning.

Thank you, Dr. Rodier for putting yourself on the line to testify. Thanks also to the HHS for allowing these reports to be made public.

Pardo letter on neuroinflamation

26 Mar

Neuroinflamation was a big subject in the Autism Omnibus. This was especially true in the “second theory of causation” hearings, which concentrated on thimerosal containing vaccines as a possible causative factor in autism.

Here’s a page from Dr. Aposhian’s presentation at the Omnibus (click to enlarge), which shows the basic logic flow.

aposhianslide76

Or, to put it simply–thimerosal gets changed to ethyl mercury which deposits mercury ions in the brain, causing neuroinflamation which causes autism.

Yes, there are a lot of of missing steps in order to prove this idea.   But, for now, let’s just think about neuroinflamation.  The term (neuroinflamation), as Dr. Aposhian makes clear in his report and slides, is somewhat new, having been coined in the 1990’s. Dr. Aposhian and others spent a lot of time discussing neuroinflamation, astrocytes and glial cells.

The research on neuroinflamation in regards to autism comes mainly from researchers at Johns Hopkins. In particular, Dr. Aposhian cites (on slide 79 of his presentation) the Vargas paper, pulling a quote:

Vargas et al., Neuroglialactivation and neuroinflammation in the brain of patients with autism. Ann Neurol57, 67-81, 2005,

“Our findings indicate that innate neuroimmunereactions play a pathogenic role in an undefined proportion of autistic patients…”

It is important to note that one of the authors on that paper was Dr. Andrew Zimmerman, whose expert report Kev recently blogged. That’s right, Dr. Zimmerman prepared an expert report for the government. The anchor author on the Vargas paper was Dr. Carlos Pardo.

It turns out that a letter from Dr. Pardo is included in the Omnibus docket as well. Here’s the introduction paragraph from Dr. Pardo’s letter:

As per our conversation last year, I would like to clarify some of the concepts regarding the role of neuroimmune response in the brain of patients with autism and the potential significance of such findings in the pathogenesis and pathobiology of the disorder.

Good–he’s trying to clarify some points of his paper. Just the sort of letter we want to read. It is rather thick on the science. Let me cherry pick one sentence, if I may:

These findings are inconsistent with the hypothesis of a potential toxic effect on astrocytes by neurotoxins or toxic material.

It strikes me that the families with claims in the vaccine court are in a really difficult position. Their lawyers and experts are arguing the thimerosal causation issue largely on the idea of neuroinflamation. The problem being that the key people in neuroinflamation and autism are experts for the other side.

The thimerosal cases depend on neuroinflamation. Does anyone else see this as a really tough battle to fight, given that the few world experts on the subject disagree with the contention that neuroinflamation in autistic brains is due to neurotoxins?

Is there an autism epidemic – the latest science

25 Mar

A new paper from Eric Fombonne is in electronic print at the journal Pediatric Research. It will apparently be published in the paper version of the journal some time after April.

The title is ‘Epidemiology of pervasive developmental disorders’ and as the name suggests, Fombonne looks at all the available quality epidemiology he can find relating to PDD’s.

This article reviews the results of 43 studies published since 1966 that provided estimates for the prevalence of Pervasive Developmental Disorders, including Autistic Disorder, Asperger Disorder, Pervasive Developmental Disorder Not Otherwise Specified, and Childhood Disintegrative Disorder.

Combining all these categories together Fombonne presents a prevalence of 60-70/10,000.

For autistic disorder, Fombonne says:

The correlation between prevalence and year of publication was statistically significant and studies with prevalence
over 7/10,000 were all published since 1987. These findings point towards an increase in prevalence estimates in the last 15-20 years.

For PDD-NOS, Fombonne explains that it is next to impossible to get accurate prevalence rates as:

This group has been much less studied in previous epidemiological studies…

Again, for Aspergers, Fombonne says that AS specific epidemiological studies are sparse but, in something of a surprise:

By contrast, other recent autism surveys have consistently identified smaller numbers of children with AS than those with autism within the same survey. In 9 out of 10 such surveys, the ratio of autism to AS prevalence in each survey was above unity, suggesting that the prevalence of AS was consistently lower than that for autism. How much lower is difficult to establish from existing data, but a ratio of 3 or 4 to 1 would appear an acceptable, albeit conservative, conclusion based on this limited available evidence. This translates into a prevalence proportion for AS which would be ? to ¼ that of autism. We therefore used for subsequent calculations an estimate of 6/10,000 for AS, recognizing the strong limitations of available data on AS.

Lastly, for CDD:

Eight studies provided data on childhood disintegrative disorder (CDD). Prevalence estimates ranged from 0 to 9.2/100,000. The pooled estimate based on eight identified cases and a total surveyed population of 406,660 children, was 2.0/100,000. The upper-bound limit of the associated confidence interval (4.0/100,000) indicates that CDD is a very rare condition, with about 1 case to occur for every 103 cases of autistic disorder.

Fombonne then tackles the question everyone wants an answer to – is there an autism epidemic?

In order to answer this accurately, he explains that there has to be tight control over incidence estimates (the number of new cases occurring in a population over a period of time) and prevalence (the proportion of individuals in a population who suffer from a defined disorder). Failure to control these gives false results. Bearing this in mind, Fombonne goes through the five approaches taken so far to try and determine if theres an autism epidemic or not.

1) Referral Statistics.
Trends in time for referral statistics are not reliable. They fail to control for things such as referral patterns, availability of services, heightened public awareness, decreasing age at diagnosis and changes over time in diagnostic concepts and practices. An example of the issues from referral statistics is:

Strong evidence of “diagnostic switching” was produced in California and in all US states indicating that a relatively high proportion of children previously diagnosed as having mental retardation were now identified as having a PDD diagnosis. Decreased age at diagnosis has also been shown to contribute to the rising numbers of children diagnosed with PDD. In the UK, Jick and Kaye (62) have shown that the incidence of specific developmental disorders (including language disorders) decreased by about the same amount that the incidence of diagnoses of autism increased in boys born from 1990-1997. A more recent UK study has shown that up to 66% of adults previously diagnosed with developmental language disorders would meet diagnostic criteria for a broad definition of PDD.

2) Comparison of cross-sectional epidemiological surveys
If I’m understanding his point here (and please correct me if I’m not) Fombonne is saying that too many epidemiological studies are uniquely designed – not enough attempt to replicate a previous study – and hence:

The most convincing evidence that method factors could account for most of the variability in published prevalence estimates comes from a direct comparison of 8 recent surveys conducted in the UK and the USA. In each country, 4 surveys were conducted around the same year and with similar age groups. As there is no reason to expect huge between-area differences in prevalence, prevalence estimates should therefore be comparable within each country. However, there was a six-fold variation in prevalence for UK surveys, and a fourteen-fold variation in US figures. In each set of studies, high estimates derived from surveys where intensive population-based screening techniques were employed whereas lower prevalence proportions were obtained from studies relying on passive administrative methods for case finding. Since no passage of time was involved, the magnitude of these gradients in prevalence can only be attributed to differences in case identification methods across surveys.

3) Repeat surveys in defined geographical areas
So this is the opposite of the above – these are studies where they are being replicated as closely as is possible. However, the issue here is that there are simply not _enough_ of these studies to form a definite conclusion. However, it may be worth noting that in the two studies Fombonne highlighted as being carried out in exactly the same way in exactly the same place to exactly the same age cohort – but just at two different times one showed no increase in prevalence whilst the other showed no increase at 4 sites and an increase at 2 sites.

4) Successive birth cohorts
This means in very large surveys with a wide age range, if the proportion of people who have autism rises this _could_ be a rise in incidence and therefore a good hint that there is an epidemic. I say _could_ as other possible causes need to be ruled out first.

…two large French surveys [used this method]. The surveys included birth cohorts from 1972 to 1985…, and, pooling the data of both surveys, age-specific prevalence showed no upward trend.

A US survey _did_ show an upward trend but:

…the increase was not specific to autism. These analyses also showed a marked period effect that identified the early 1990s as the period where the prevalence estimates started to go up in all ages and birth cohorts, coinciding closely with the inclusion of PDDs in the federal Individual with Disabilities Educational Act (IDEA) funding and reporting mechanism in the US.

5) Incidence studies
The few incidence studies did show incidence trends rising over short periods of time. As noted in point 4) above, this _could_ be attributed to an autism epidemic. However –

…none of these studies investigations could determine the impact of changes over time in diagnostic criteria, improved awareness and service availability on the upward trend.

Contrary to what people who _want_ there to be an autism epidemic, these are non trivial reasons. It stands to reason that if (for example) Birmingham, UK – the countrys second city, goes from having zero service availability and no means of diagnosis in 1960 to having numerous types of service availability both publicly and privately funded and a _lot_ of means of diagnosis in 2000 there will be a _lot_ more autistic people in Birmingham. A hell of a lot. When we then consider that the diagnosis criteria has widened massively than we go from a hell of a lot more autistic people to a _whole hell_ of a lot. If we _also_ consider that people who used to carry one kind of diagnosis are now being swapped to autism then we go from a whole hell of a lot to a descriptive term beyond my ability. This isn’t even science – its basic common sense. The only issue is – ‘a whole hell of a lot’ is not a very accurate measurement.

Fombonne closes by saying that – based on the available data – we still cannot really say one way or the other if there has been an autism epidemic. Remember when you read the quote below that its _incidence_ that gives us an epidemic.

Current evidence does not strongly support the hypothesis of a secular increase in the incidence of autism but power to
detect time trends is seriously limited in existing datasets. Whilst it is clear that prevalence estimates have gone up over time, this increase most likely represents changes in the concepts, definitions, service availability and awareness of autistic-spectrum disorders in both the lay and professional public. To assess whether or not the incidence has increased, method factors that account for an important proportion of the variability in prevalence must be tightly controlled. The possibility that a true change in the underlying incidence has contributed to higher prevalence figures remains, however, to be adequately tested.

Oldstone letter in the Omnibus docket

25 Mar

When I found that the Autism Omnibus Proceeding expert reports were public, the first one that caught my eye was by Andrew Zimmerman. Obviously, it caught Kev’s attention too 🙂

But, I have only a brief time available today, so I will start with this letter by Dr. Michael Oldstone. It is brief enough that I have copied the body in its entirety below.

To summarize, Rick Rollens asked Dr. Oldstone to consider collaborating with Dr. O’Leary and Dr. Wakefield on the Autism/MMR question. It was a good move on Mr. Rollens’ part, as Dr. Odlstone is one of the preeminent researchers in viral pathogenesis. Has been for decades.

Before agreeing to collaborate, Dr. Oldstone wanted to check on the quality of the results coming out of the O’Leary laboratory. Dr. Oldstone sent tissue samples to Dr. O’Leary’s laboratory, some with measles virus, some without. Dr. O’Leary tested them–and got the wrong answer 20% of the time. Dr. Oldstone sent another batch of samples, some duplicates from the first batch. Not only did Dr. O’Leary’s laboratory get 20% wrong again but, in Dr. Oldstone’s words:

Most troublesome, some samples, when tested twice under different code numbers ‘switched’ from positive to negative or from negative to positive. On this basis of inaccuracies of their PCR test, I declined from further working with either Drs. Wakefield or O’Leary.

This goes directly towards the question of the quality of the data coming from Dr. O’Leary’s laboratory. This is a big question. The Hornig study came out last year, an attempt to replicate Dr. Wakefield’s research. In one of the strangest moves I have ever seen by a researcher, Dr. Wakefield claimed that this study actually supported his research by demonstrating that Dr. O’Leary’s lab is capable of making accurate PCR measurements. Dr. Wakefield neglected the obvious point–being accurate today doesn’t mean one was accurate yesterday. He also neglected the suggestion (made by Dr. O’Leary himself at the press conference for the Hornig study) that Dr. Wakefield’s samples could have been contaminated.

Well, here is a good example that Dr. O’Leary’s laboratory was not making accurate measurements. This was iin the “early 2000’s”. Note that the Uhlman paper (Dr. Wakefield’s team’s paper supposedly finding measles virus in gut tissue) came out in 2002–the same time period.

Below is the letter, dated Oct. 12, 2007, from Dr. Oldstone to Dr. Brian Ward.

Dear Dr. Ward:

I recently became aware that my work in the field of viral persistence is being quoted in support of the hypothesis that the measles virus component of the measles-mumps-rubella (MMR) vaccine is supposedly associated with the development of autistic spectrum disorder (ASD).

Measles virus has been a focus of my laboratory for many years so this autismlmeasles link has been of interest to me. Further, I should state up front that I see at present no evidence whatsoever for such a link.

In the early 2000s I was asked by Rick Rollens to consider a collaborative grant between my laboratory and that of Drs. Wakefield and O’Leary. Prior to making a decision, I decided to assess the performance of Dr. O’Leary’s PCR-based assays targeting measles virus. My laboratory generated samples from tissue culture cells infected with MV as well as tissue samples from our transgenic mouse model of MV infection (including gut and brain tissues), which were coded and sent to the O’Leary laboratory. Samples had varying titers of measles virus as well as appropriate negative control and measles virus positive samples. The arrangement was informal in that the samples were only sent to Dr. O’Leary for testing. After receiving Dr. O’Leary’s results, the code was broken and I discovered that approximately 20% of the samples were incorrect as to the
presence or absence of measles virus. I reviewed the results with Dr. O’Leary as well as his protocols for preparing his assay, which I found to be sound and decided that perhaps there may have been some unknown error and a second set of samples should be sent. This second set was again coded anew and contained both new samples and several original samples. The results of the second round were no better with again approximately 20% of the samples misidentified by Dr. O’Leary’s laboratory. Most troublesome, some samples, when tested twice under different code numbers ‘switched’ from positive to negative or from negative to positive. On this basis of inaccuracies of their PCR test, I declined from further working with either Drs. Wakefield or O’Leary.

Sincerely,
Michael B.A. Oldstone, M.D.
Head, Viral-lmmunobiology Laboratory

Omnibus Expert Reports

24 Mar

As noted in Kev’s recent post, the expert reports from the respondent (government side) have been made public.

The above link is a pdf file. The boxes in the pdf file are live links. I.e. click in the boxes and you will get the expert report.

I am very glad they did this. The best autism experts were pulled in to the Omnibus, and it is great to have the chance to refer to what they wrote. Many of the experts didn’t testify, so this is where you and I can see what they had to say.

I’ve read through some. They are good references. They also support very well what the Special Masters stated in their decisions: this wasn’t a close call. The petitioners just didn’t have good evidence, and the evidence against them was very good.

I’ll definitely be blogging a number of these. They are well worth discussing.