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Questions and answers with the thimerosal-autism study author

13 Sep

It is a safe bet that there would be a lot of questions arising from the latest study, which shows no link between thimerosal exposure and autism. I thought there would be some interviews in the press covering most of the obvious questions, so I decided to ask some questions of my own of the study’s lead author, Cristofer Price of Abt associates.

I was very interested in the more complete discussion in their Techical Reports and data. I was also interested in how these results might apply to the idea that there are “too many” vaccines given “too soon”. Mostly I was interested in why this study took so long to get published give the CDC’s statements after the Thompson study of 2007–statements which indicated that this follow-on study should be available within about a year or so.

Below is the exchange:

First: you cite two Abt reports from 2009 on the subject:

Price C, Robertson A, Goodson B. Thimerosal
and Autism. Technical report. Vol I. Bethesda,
MD: Abt Associates Inc; 2009

I can’t find them on your site at this time. Are they there or will they be made available when the embargo is lifted?

[Response: The tech reports will be up on the CDC and Abt web sites on Monday. ]

Will the data be made available as was done with the Thomson(2007) study? If so, how would one access it?

[Response: Yes, the process for obtaining the data will be very much like the process that was in place for the Thompson(2007) study. Instructions for how to access the data and a data use agreement, etc. will be up on the CDC web site on Monday. The terms specified in the data use agreement are similar to those from the prior study. ]

As to the paper, I see that the results are the same for autism with and without regression. Are there any other issues of severity which were checked (e.g. level of intellectual disability, seizures) which were also monitored?

[Response: We did do a sub-analysis where AD cases with low cognitive functioning were excluded (see technical report on Monday for full details and results) Analysis of the subgroup of AD cases where children with low cognitive functioning were excluded was motivated by the following concern. Because children who are non-responsive during the assessment process are more difficult to assess, it can sometimes be difficult to determine whether children with severe developmental delay actually have autistic disorder. If the imprecision of the assessment process for such children resulted in inclusion of children without AD in the AD group, then we would expect that the estimate of the relationship of exposure to AD risk could be attenuated. Therefore, an outcome category for AD with low cognitive functioning excluded was created and its relationship to exposure was estimated. The results for this subgroup were very similar to those for the overall analysis.]

There are children (both case and control) who have 0 mercury exposure from vaccines in all categories. Are there children in all these categories who are unvaccinated?

[Response: I don’t have the answer to this handy. I know that there were a few kids in the sample that had zero vaccine receipts, but I don’t think they were in all of the categories because there were few of them. Most of the kids with 0 mercury exposure received at least some vaccines, but they were thimerosal free.]

To some extent, mercury exposure from vaccines could be used as a proxy variable for vaccine exposures. I.e. the amount of mercury would be somewhat proportional to the number of vaccines received. Are there any trends in just number of vaccines and autism? I.e. anything that would address the “too many, too soon” slogan? I do see that you discuss this somewhat on page 661

[Response: In the technical report (Volume II, Chapter 16) I show data on the the cumulative numbers of vaccines recieved as children aged. It shows that the cases and controls got the same numbers of vaccines. That chapter was not designed specifically to address your question about “too many too soon”, but it does show cases did not get more, sooner than controls.]

After Thomson(2007) came out, I recall that the CDC webpage suggested that your present study would be out in about a year. Why has this study taken so long to reach the public?

[Response: I’m not sure why the CDC web page had the overly optimistic suggestion that it would be out in about a year. To understand the timeline, I will need to explain some things about the phases of analysis, then the process of drafting the paper and getting it published. This is going to be a bit long winded, but part of it I am cutting and pasting from the technical report:

The study protocol was developed by a design group led by Abt Associates, Inc. working in close consultation with Principal Investigators from the
Centers for Disease Control and Prevention (CDC), Principal Investigators, Data Managers, and Study Managers from the each of the three HMOs, and with the study’s External Expert Consultants. Prior to recruitment and data collection, a detailed analysis plan was written for the study that specified the research questions, study design, eligibility criteria, sampling plan and target sample sizes, the form of the statistical models that would be used, the specific hypotheses to be tested, decision rules for categorizing outcome classifications, the coding of exposure variables,
the list of covariates to be used as statistical control variables, the coding of each of those variables, and decision rules for the retention or omission of each covariate in the final analysis models.

By agreement among the members of the design group, data analysis for the study was to be completed in two phases. In the first analysis phase, analysts at Abt Associates were to carry out as closely as possible the analyses specified in the plan and to do only the analyses specified in the plan. At the end of this phase, all members of the design group were invited to a meeting in Washington, DC where the first round, preliminary results were presented to the group. Prior to that meeting, the results of analyses linking exposures to outcomes had not been shared with anyone outside of Abt Associates. The second phase of analysis began with the meeting in Washington, DC. At that meeting, the design group considered the results and generated new hypotheses and questions that were to be pursued in the second phase. Over the ensuing months design team members provided written comments on the results of the preliminary analyses and made suggestions for additional analyses. The current report includes results from both phases.

The meeting in DC described in the paragraph above took place in May of 2008. We gave all of the members of the design group a couple of months to give feedback and suggestions on the analyses that they wanted in Phase II. There was a lot of back and forth there. The technical report includes results from both phases. We were well into 2009 before we (at Abt) had made it all the way through those second phase analyses. Then, drafts of the manuscript had contributions from a large number of authors (which takes a lot of time) and we sent drafts to our External Expert Consultants, made changes, replied to queries etc, then a draft had to go through CDC review which takes time, then we the publication process (getting a manuscript published in a peer-reviewed journal) takes a surprisingly long time. So, here we are in 2010.]

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.

Congenital Rubella Syndrome: a Novel Form of Mercury Poisoning?

13 Sep

I considered titling this: A peak into the upcoming book “Age of Autism?” as this seems to show us the sorts of arguments that will be made in that book.

One of the known environmental causes of autism is Congenital Rubella Syndrome, or CRS. This was discussed as part of a presentation to the IACC, What Causes Autism? The Case for an Environmental Contribution, by Dr. Philip Landrigan. (video is here, starting at about minute 79. Sorry it doesn’t embed).

In the question/answer session for that presentation on at about 114 minutes into the IACC meeting) Lyn Redwood of SafeMinds brought up a new argument–that CRS induced autism may be due to mercury. It turns out that in the 1950’s gamma globulin therapy was started as a means of preventing CRS. Gamma Globulin was injected into pregnant mothers who to prevent or reduce the rubella infections. This exposed the mother and fetus to mercury and should be considered the cause of the autism according to Ms. Redwood.

I must admit that when I heard this question I thought: “Well, here is one of the talking points we will hear from the upcoming book, ‘Age of Autism’, by Mark Blaxill and Dan Olmsted”. Their book appears to be an attempt to tie all of autism (and many other conditions) to mercury, including, I suspect now, CRS. There are other loose ends they will undoubtedly bring up and tie into the mercury hypothesis (like the existence of autistics who were born before thimerosal was invented. That will be interesting to read).

There is at least one big reason why CRS was possibly not linked to autism before Stella Chase’s work in the 1970’s. Congenital Rubella Syndrome causes major disability. Severe to profound mental retardation. There are big spikes in the California Department of Developmental Services data for severe and profound mental retardation corresponding to the CRS outbreaks of the 1960s. Why bring this up? Because for the first two decades after Kanner’s original paper, many people considered intellectual disability (mental retardation) and autism to be completely separate.

From Infantile autism reviewed: a decade of research, a review article written in 1981:

One of the chief problems has been how to handle the questions of mental retardation and organic brain disease, issues especially troublesome with regard to infantile autism. When Kanner (1943) first described the diagnostic features, he also remarked that the condition bore no resemblance to any known neurological condition and implied that autistic children had a basically normal intelligence. For over two decades afterwards, diagnosticians generally believed that the presence of mental retardation or neurologic signs ruled out the diagnosis of infantile autism in the Kannerian sense, even if the child met all behavioral criteria (Eisenberg 1966). Thus diagnosis was frequently one dimensional; a child was labeled as afflicted with either infantile autism or mental retardation, not both.

Or, to put it another way, what many people today call “Kanner’s Autism”, with intellectual disability and/or apraxia, is not what Kanner and most of the people of his time thought of as autism.

But, data, as they say, there’s a funny thing about evidence. Real data is worth more than all these blogger discussions. The paper out today from Pediatrics included immune globulins in their analysis and showed that mercury exposure prenatally and in infancy and found that these exposures did not increase the risk of autism.

Then again, the funny thing about evidence is that it is repeatable. Two previous papers showed no link between immune globulins and autism:

Maternal Rh D status, anti-D immune globulin exposure during pregnancy, and risk of autism spectrum disorders


Lack of association between Rh status, Rh immune globulin in pregnancy and autism.

So, if I am correct and “Age of Autism” the book claims immune globulins *are* a cause of autism, what can we say? We can say that the funny thing about evidence is that some people are not swayed by it. Some people will continue to push the mercury hypothesis forever.

Thimerosal in vaccines did not cause an autism epidemic

13 Sep

There have been two main theories linking vaccines to an “epidemic” of autism. Both theories have been studied. Both have been heard in the courts. Neither theory had a sound scientific basis and epidemiological data has shown that neither theories explained the increase in autism prevalence in the last 20 years.

First it was proposed that the MMR vaccine resulted in persistent measles infections that lodged in the intestines of children leading to “leaky guts” and that harmful substances were leaked into the blood, traveled to the brain and resulted in autism symptoms. This was proposed by Dr. Andrew Wakefield and has since been shown in epidemiological and other studies to be unsound. (This theory morphed for the Omnibus Autism Proceeding, the vaccine court. The argument there was that the measles virus itself traveled to the brain. Again, it is not supported by epidemiological data and is not scientifically sound).

The second theory was that mercury in vaccines from a compound called thimerosal caused autism. In that theory, it was proposed that autism symptoms were similar to mercury poisoning (autism was a “novel” form of mercury poisoning). This theory was not scientifically sound as autism symptoms are not like mercury poisoning. Previous epidemiological studies have also shown thimerosal was not behind the rising numbers of people diagnosed with autism.

In 2007 there was a study which looked at 1,000 kids aged 7-10 to see if various neurological symptoms were more prevalent in those who received higher exposures to thimerosal. Orac at Respectful Insolence blogged it and Kev posted that piece here on LeftBrainRightBrain as well. That study showed indications that in some measures children may perform more poorly with thimerosal exposure. It also showed that in some measures children may perform better with thimerosal exposure. This mixed result is (a) not very strong in either direction and (b) not very surprising when you look at a lot of different measures at the same time. Chance will result in some measures positive, some negative.

The 2007 study was published in the New England Journal of Medicine as Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years, by Thompson, et al.. (Thompson (2007))

What was missing in that report was a direct study of autism. Given the numbers of children (1,047) selected, there would only be about 10 kids with ASD expected in the group. This is too few for a strong conclusion on autism. At the time of that study it was noted that another study would follow concentrating on autism alone.

That study has just been published in the journal Pediatrics as Prenatal and Infant Exposure to Thimerosal From Vaccines and Immunoglobulins and Risk of Autism. They studied “256 children with ASD and 752 controls matched by birth year, gender, and [managed care organizations]”. I will give some details here. I expect the treatment on the Science Based Medicine and Steven Novela’s Neurologica blogs to cover the science thoroughly should you wish more detail.

Short answer: thimerosal exposure doesn’t cause an increased risk of autism. Neither thimerosal from vaccines given to the children nor thimerosal from products like Rhogam are behind the increase in autism prevalence we have seen.

It is worth noting that the authors looked at autism with and without regression.

Here is the abstract:

OBJECTIVE: Exposure to thimerosal, a mercury-containing preservative that is used in vaccines and immunoglobulin preparations, has been hypothesized to be associated with increased risk of autism spectrum disorder (ASD). This study was designed to examine relationships between prenatal and infant ethylmercury exposure from thimerosal containing vaccines and/or immunoglobulin preparations and ASD and 2 ASD subcategories: autistic disorder (AD) and ASD with regression.

METHODS: A case-control study was conducted in 3 managed care organizations (MCOs) of 256 children with ASD and 752 controls matched by birth year, gender, and MCO. ASD diagnoses were validated through standardized in-person evaluations. Exposure to thimerosal in vaccines and immunoglobulin preparations was determined from electronic immunization registries, medical charts, and parent interviews. Information on potential confounding factors was obtained from the interviews and medical charts. We used conditional logistic regression to assess associations between ASD, AD, and ASD with regression and exposure to ethylmercury during prenatal, birth-to-1 month, birthto-7-month, and birth-to-20-month periods.

RESULTS: There were no findings of increased risk for any of the 3 ASD outcomes. The adjusted odds ratios (95% confidence intervals) for ASD associated with a 2-SD increase in ethylmercury exposure were 1.12 (0.83–1.51) for prenatal exposure, 0.88 (0.62–1.26) for exposure from birth to 1 month, 0.60 (0.36–0.99) for exposure from birth to 7 months, and 0.60 (0.32– 0.97) for exposure from birth to 20 months.

CONCLUSIONS: In our study of MCO members, prenatal and early-life exposure to ethylmercury from thimerosal-containing vaccines and immunoglobulin preparations was not related to increased risk ASDs. Pediatrics 2010;126:656–664

My guess is that there will be much discussion of the methods on many websites. For now, here are the data from Table 2 and Table 3.

Table 2 (click to enlarge)

Table 3 (click to enlarge)

As with Thompson (2007) the authors will make longer reports available on their website and will allow access to the data.

This study is not the first of its kind. Here are a few of the large studies which have shown a lack of association between thimerosal exposure and autism in the past.

Thimerosal and the Occurrence of Autism: Negative Ecological Evidence From Danish Population-Based Data

Safety of Thimerosal-Containing Vaccines: A Two-Phased Study of Computerized Health Maintenance Organization Database

Thimerosal Exposure in Infants and Developmental Disorders: A Prospective Cohort Study in the United Kingdom Does Not Support a Causal Association

Autism and Thimerosal-Containing Vaccines Lack of Consistent Evidence for an Association

There are more.

One question is whether this will finally quiet those claiming an autism epidemic caused by mercury in vaccines. Unfortunately, I sincerely doubt it. This study included Sallie Bernard of SafeMinds in the acknowledgments. Ms. Bernard was also involved in the Thompson study of 2007. At that time she was listed as a “dissenting” member of the team. She submitted a letter to the NEJM discussing the reasons for her dissention, Perhaps the lack of the word “dissenting” this time is a good sign. I’ll wait and see.

The main question is how much impact this will have on the next generation of families with autistic children. I can’t but wonder that the age of the mercury hypothesis has seen its peak. Not only in research but in general acceptance.

Sharyl Attkisson blogs the Hannah Poling settlement

10 Sep

I had forgotten Sharyl Attkisson. She is a reporter for CBS news who has covered vaccines in the past, but has been silent on the issue for the past year or more.

Her recent piece shows exactly the sort of reporting that frustrated me in the past: Family to Receive $1.5M in First-Ever Vaccine-Autism Court Award

In that piece she links to her piece from 2008 on the Hannah Poling case: Vaccine Case: An Exception Or A Precedent?

Here’s a quote from that earlier piece:

While the Poling case is the first of its kind to become public, a CBS News investigation uncovered at least nine other cases as far back as 1990, where records show the court ordered the government compensated families whose children developed autism or autistic-like symptoms in children including toddlers who had been called “very smart” and “impressed” doctors with their “intelligence and curiosity” … until their vaccinations.

They were children just like Hannah Poling.

What’s still being debated is whether the Poling case is an exception … or a precedent.

So, which is it? Were there children “just like Hannah Poling” or is this the “First-Ever Vaccine-Autism Court Award”?

Actually, it is neither. This isn’t the first vaccine court award involving autism, and the other cases are not “just like Hannah Poling”.

For real information on the other nine cases, read Kathleen Seidel’s piece on Neurodiversity.com. Few, professional or amateur, can compare the the thoroughness of Kathleen Seidel. For example, one case (the first I read involving autism from the vaccine court) is Suel v. HHS. Young David Suel had tuberous sclerosis, a condition known to be associated with autism and epilepsy. Epilepsy occurs in about 60 to 90% of individuals with TS. Autism occurs in about 25-50%. David Suel’s case was declared to be a “table injury” wherein the seizures began within a set period after his DPT vaccination. What is notable about that is the table for DPT was later changed–when it was shown that DPT was not responsible for inducing seizure disorders. In other words, had David Suel been vaccinated, or just filed, after the change in the table, he likely would not have been awarded damages.

“They were children just like Hannah Poling”? Is tuberous sclerosis just like mitochondrial disease? (answer: not even close).

Shall we go on? In her recent piece, Ms. Attkisson states:

In 2002, Hannah’s parents filed an autism claim in federal vaccine court. Five years later, the government settled the case before trial and had it sealed

Not accurate. The court did not “settle” the case in 2007. They conceded the case, and they were in the process of completing the settlement when someone leaked the information to the press. The government did not “seal” the case–it is standard procedure to keep this information confidential until the settlement is completed.

But that doesn’t make a good story, does it?

Ms. Attkisson goes on:

In acknowledging Hannah’s injuries, the government said vaccines aggravated an unknown mitochondrial disorder Hannah had which didn’t “cause” her autism, but “resulted” in it. It’s unknown how many other children have similar undiagnosed mitochondrial disorder. All other autism “test cases” have been defeated at trial. Approximately 4,800 are awaiting disposition in federal vaccine court.

Mito-autism was a big thing for a while there. David Kirby took the story and ran with it–making a lot of mistakes along the way and propagating a lot of misinformation. It is unknown how many other children have similar disorders–but the researchers who studied cases like Hannah Poling have stated that cases such as hers are “rare”.

“All other autism “test cases” have been defeated at trial”.

What is conspicuous about the other “test cases” is that in none of them was it argued that the children were like Hannah Poling–i.e. the attorneys did not argue that a mechanism of autism through mitochondrial dysfunction aggravated by vaccines existed. In fact, one child named as a test case was pulled from that slot in order to argue that mitochondrial based case. The expert report filed for that child (since pulled from the Omnibus website) did not argue mitochondrial disorder or dysfunction at that time. In other words, the idea of a mitochondrial disorder being linked to autism was so alien from the cases being made by the attorneys for the families in the Omnibus that this child had to argue the case separately.

It is often pointed out that many autistics may have mitochondrial dysfunction. This is based largely on studies out of Portugal. It is left implied, and it is often believed that mitochondrial dysfunction means vaccine injury in these cases. This was the impression that David Kirby put forth and it was clearly wrong. First, mitochondrial disorders are a very broad spectrum. The type that Hannah Poling has is not the same as those detected in most autistics. Second, most reports of mitochondrial disorders and autism, including the Portugal studies, do not involve regression. Third, even amongst those children reported by the groups that identified Hannah Poling, regression was often idiopathic or followed fever clearly independent of vaccination.

I do not expect Ms. Attkisson to present the following (quality) information, so I will repeat it here:

Here are the answers to some questions posted to mitochondrial medicine experts and their answers:

When asked, to respond to the position: ‘‘I view the risk of vaccination in known metabolic disease patients to generally be outweighed by the risk of the infectious diseases being vaccinated against”

63.2% strongly agreed
31.1% agreed
0.9% disagreed
and 0.9% strongly disagreed.

Asked about the opinion that the risk of vaccination in metabolic disease was ‘‘greater than the risk of the infectious diseases being vaccinated against”

52.9% strongly disagreed
40% disagreed
3.5% agreed
and none strongly agreed

A busy week in vaccine-injury news: the Cedillo appeal

4 Sep

The past week has had three somewhat major news events in the world of vaccine injury: the denial of the Cedillo appeal, the award of damages in the UK for an MMR case and the damages award in the Hannah Poling case. I thought I would write about them all, but the Cedillo appeal part is already long so I will leave the other subjects for another time.

The Cedillo Appeal

Kev blogged the denial as Cedillo appeal denied. I had blogged the hearing in June as Another appeal heard in the Autism Omnibus, then blogged the actual audio from the hearing as Audio of the Cedillo appeal part 1 and Audio of the Cedillo appeal part 2.

The arugument used in the Omnibus Autism Proceeding for MMR causing autism is basically the model that grew out of the work of Andrew Wakefield: that measles virus (MV) from vaccines persisted in the body, particularly in the digestive tract. Wakefield’s theory involved the MV infection causing intestinal permeability which allowed substances to “leak” out into the system (the “leaky gut” hypothesis). The Cedllio’s attorneys argued that the measles virus itself traveled to the brain, causing inflammation and autism.

This is not the first appeal for the Cedillo family, or for the test cases in the Omnibus. It is likely the last, however. The next step would be the U.S. Supreme Court. The Supreme Court would be unlikely to hear an appeal. The Supreme Court does not hear all the cases submitted, instead choosing to hear mostly cases which clarify points of law. The Cedillo appeal so far has not been about the laws for the most part but about the procedure of the case. One exception is the question of whether the correct standard was applied to reviewing the admissibility of the evidence. The Court used the Daubert standard, which the Cedillo’s attorneys argued was incorrect. This is not the first time the Court used Daubert, and it is not the first time the appeals court upheld it.

The other arguments made include whether the testimony and reports of Dr. Stephen Bustin should have been allowed. Dr. Bustin’s reports were obtained very shortly before the hearing and were based on closed documents from a U.K. proceeding on MMR and autism. The Cedillo’s attorneys argued that they were unable to prepare a counter argument to Dr. Bustin on short notice and that since they did not have access to the underlying data and documents. In a civil court, these arguments would have carried much weight. However, in the vaccine court, much flexibility is allowed. In this case, the Special Master allowed the evidence to be heard, and gave the Cedillo’s attorneys over a year to obtain the background data from the UK and mount a counter argument.

The Cedillo’s attorneys did not attempt to obtain the background data for the Bustin testimony in year that followed the hearing. Yes, it isn’t that they were unsuccessful, they didn’t try to obtain it. They stated that their consultants in the UK advised them that it was unlikely that they would be able to obtain the documents without the permission of the experts. However, Dr. Bustin gave his permission.

From the appeals court decision:

Petitioners considered making such a re-quest from the UK court, but never did so. They contend that British counsel informed them that it was unlikely that the UK court would permit disclosure of the expert reports without the consent of the experts, which peti-tioners stated that they could not obtain. But Dr. Bustin did consent to the release of his reports. Once his consent for the release of his reports had been obtained by the government, there is no reason why the data underlying his reports could not also have been requested

Dr. Bustin’s testimony focused on a critical part of the argument used to claim that MMR causes autism: the claimed presence of measles virus in the bodies of autistics like Miss Cedillo. Dr. Bustin is arguably the worlds top expert on PCR, the method used by the Unigenetics Laboratory to test tissue samples for measles virus. Dr. Bustin discussed at length multiple reasons why the Unigenetics Laboratory results were not reliable.

A few points to be made here.

(1) The Cedillo’s attorneys presented an expert (Dr. Kennedy) to claim that the Unigenetics laboratory was reliable. Dr. Kennedy also had worked on the UK litigation and Dr. Kennedy’s underlying data were also under seal in that litigation. In other words, the Cedillo’s attorney’s were asking that the Special Master apply one standard to the government’s witness (rejecting his report without the underlying data) while applying the exact opposite standard to their own witness (Dr. Kennedy, who also didn’t have the underlying data).

(2) Michelle Cedillo was one of three “test cases” used to test the question of “general causation”. The other two children used as test cases did not have evidence of persistent measles virus in their bodies.

There is only one paper with reliable data showing the presence of measles virus in the tissues of an autistic child. This paper came out after the Cedillo hearing. The paper: Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study. In that study they found measles virus in one autistic child, and in one non-autistic “control”. The Cedillo’s attorney’s argued that this was “significant new evidence” that showed the reliability of the Unigenetics laboratory.

I found it very odd that a paper titled “Lack of association between Mealses Virus Vaccine and Autism with Enteropathy” would be used as evidence for an association between measles virus vaccine and autism. But the argument is that this paper validates the Unigenetics laboratory as being able to produce reliable results. The argument is not valid, and the court did not agree with it. The work done by Unigenetics on Miss Cedillo was performed in 2002. The research on the paper was performed much later, after significant criticism was already levied against Unigenetics. Quite simply put, it is possible that Unigenetics “cleaned up its act” by the time of the recent paper.

(3) It was noted that the arguments about Dr. Bustin’s testimony were essentially moot, as the Special Master would have come to the same decision without his testimony.

(4) It was also noted that the appeals court had already decided on Dr. Bustin’s testimony in an appeal mounted by the attorneys for the Hazelhurst family (another of the Omnibus test cases).

The Cedillo’s attorneys further argued that it was unfair that evidence was brought in from the other “test case” hearings (Hazelhurst and Snyder). The appeals ruling noted that the Cedillo hearing was not a stand-alone proceeding. As a test case in an Omnibus Proceeding, evidence from all the test cases would be used to answer the question of general causation. I was surprised at the time of the appeal that the Cedillo’s attorneys were arguing that they were not actively monitoring the other test case hearings. What, in the end, is the point of an Omnibus Proceeding or a “petitioners steering committee” of the petitioners are not acting in some way as a group?

The Cedillo’s attorneys argued that the Special Master did not give enough weight to Miss Cedillo’s doctor, Dr. Krigsman, who stated that her condition was caused by MMR. The fact is that the Special Master rejected Dr. Krigsman’s argument with good cause:

He [the special master] also concluded that Dr. Krigsman’s opinion should be rejected because 1) he relied on the discredited Unigenetics testing in forming his opinion, 2) he misunderstood Michelle’s medical history and his testimony was inconsistent with her medical records, and 3) his conclusion that Michelle suffered from chronic gastrointestinal inflammation was substantially out-weighed by Michelle’s medical records and the testimony of the government’s experts.

The Cedillo’s attorneys argued that sufficient weight was not given to Miss Cedillo’s other physicians whom, they assert, associated her condition with the MMR vaccine:

Petitioners cited nine notations in Michelle’s records from eight individuals, including four physicians who treated Michelle and four non-physicians who exam-ined Michelle, in which the treating physicians mentioned her vaccinations, as support for the proposition that these individuals concluded that her autism was caused by her MMR vaccine.

The appeals court disagreed:

The Special Master did not err in failing to afford sig-nificant weight to the opinions of Michelle’s treating physicians. As the Special Master observed in his deci-sion, in seven of the nine notations, the physician was simply indicating an awareness of a temporal, not causal, relationship between the fever Michelle experienced after her MMR vaccine and the emergence of her autistic symptoms sometime thereafter. Initial Decision, slip op. at 100. In one of the other notations, the physician sim-ply noted that an exemption for Michelle from vaccination requirements could be arranged. In the other notation, the physician speculated that Michelle’s fevers might have caused her neurological abnormalities. However, he expressly stated that it would be “difficult to say” whether this was “a post-immunization phenomenon, or a separate occurrence.” Id. at 100. Thus, “none of the treating physicians concluded that the MMR vaccine caused Michelle’s autism.” Final Decision, 89 Fed. Cl. at 176. The Special Master

In the end, the appeals court decision takes on the arguments by the Cedillo’s attorneys point by point and refutes them. The closest the Cedillo’s attorneys got to making a point stick was in the case of Dr. Bustin’s testimony, which the appeals court stated:

We agree with petitioners that the government’s fail-ure to produce or even to request the documentation underlying Dr. Bustin’s reports is troubling, but we think that in the circumstances of this case, that failure does not justify reversal.

The fact of the matter is, the petitioners in general, and the Cedillo’s in specific, did not have a good case for MMR causing autism. The mechanism they proposed was not sound, the data they had was poor and incomplete and the experts speaking for the government were excellent and refuted the petitioner’s arguments. The Omnibus cases were, as the Special Masters noted, not close.

MMR vaccine damaged man

30 Aug

Jackie Fletcher is well known to many – she routinely insists the MMR jab is dangerous despite reams of evidence to the contrary. However, a panel in the UK has found that her son, Robert, was damaged by the MMR vaccine he was administered.

I nearly didn’t blog about this. Why? Well, this blogs predominant focus is autism and Robert did not and does not have autism. The panel in this case found that the MMR caused seizures and mental retardation. Its difficult therefore to get a ‘hook’ into this story. As Mike Fitzpatrick is quoted as saying in the Daily Mail:

It is a very important principle that parents should be compensated in cases of this kind…

and he’s absolutely right. Thats why the Vaccine Damage Payment Unit exists in the UK.

Like any other form of medical procedure, vaccines are not 100% safe. I can’t recall anyone anywhere ever making that claim. What they _are_ however, is very safe indeed. Robert Fletcher was injured and has been compensated. I might even agree with his mum that the amount is ‘derisory’. Robert will need full time care all of his life and £90,000 ($140,000) is nowhere near enough. However, campaigners uninterested in Robert’s day to day needs say that:

Campaigner Polly Tommey, who edits the magazine The Autism File and believes her son Billy is autistic because of MMR, says: ‘This is fantastic news. Now doctors can’t tell me that the MMR is safe.

‘This payout is evidence that it is not safe. It’s interesting that they will look at epilepsy and not autism, and you have to ask why.

‘Is it because the compensation would be billions?’

I very much doubt that any doctor, anywhere has ever told any recipient anywhere that any vaccine is 100% safe. If they did, they were liars.

However, this payment, far from being ‘evidence that it is not safe’ (a bizarre claim) is more like a recognition that the Vaccine Damage Payment system is working as it should. A man was vaccine damaged and was compensated as a result.

As for the claim that ‘they’ will not look at autism, this is simply incorrect. Robert, does not have autism and therefore it would be impossible in this case to look at autism. I would imagine if someone with autism was adjudged to be damaged by their MMR vaccine, Ms Tommey might have a point. As that has not happened, she does not. This kind of fear-mongering by the likes of Tommey is no doubt why the panel made the clear point:

We would stress that this decision is fact-specific and it should not be seen as a precedent for any other case.

In particular, it has no relevance to the issue… as to whether there is a link between the MMR vaccine and autism.

And Fletcher goes on to claim:

Claims for autism are not considered. There are 120 MMR cases waiting to be heard, but none is for autism…

So why should that be? Why is autism apparently ‘excluded’?

Its because the science – both epidemiological and clinical clearly shows that MMR does not cause autism. And that is not the odd paper here and there. We are talking about overwhelming science that shows that the whole autism/MMR connection is simply false and was built up by one man too stupid to admit his clear errors and a mass media keen to build sensation out of this same man’s ego.

Tommey, Fletcher and all others who believe that there’s some kind of conspiracy afoot to block autism from MMR causation cases need to understand the science involved and that unless some new science is forthcoming that establishes MMR as a causative agent in regards to autism then the simple fact of applying for compensation listing the MMR as a cause of their child’s autism is _always_ going to be an immediate strikeout.

Campaigners need to start seeing this event for what it _really_ is – compensation for a vaccine damaged man – and not as what it isn’t – evidence that MMR is inherently unsafe or that theres some mysterious conspiracy to prevent autism from being linked to MMR.

Quick Q&A with APC study lead author

26 Aug

I recently blogged about a study that linked APC dysfunction with autism and learning disability. Two questions interested me so I wrote to lead author Michele Jacob to ask them.

Hi Dr Jacob,

My name is Kevin Leitch, I own and edit a popular blog on autism and am also father to an autistic daughter.

I found your recent study very interesting and had questions that I’d like to ask you and hopefully you’d give me permission to discuss your answer on the blog?

My questions are –

1) is there any set of circumstance in which APC dysfunction can occur ‘in the wild’ e.g. could a child be given something that then ‘turned’ them into an autistic person by negatively affecting APC function?

2) If there *is* , is there a way that this dysfunction might be reversed or at least modified somewhat?

My own take on this is that the answer to both questions would be ‘no’ but I have no understanding of APC function and a laymans understanding of genes in general.

Many thanks in advance for both your fascinating study and any time you can offer me in answering my questions.

She responded:

Hi Kevin,

Thanks for discussing our work in your blog. I am delighted our work interests you.

I think the short answer to both questions is no. The only way to cause APC dysfunction is via gene mutations. It’s function can be modified, enhanced or reduced, by signaling events in cells, but these changes are not large enough to have effects on behavior.

Loss of function mutations in the APC gene are inherited or occur sporadically. The symptoms associated with the sporadic mutations will depend on the cell type. APC is present in all cells of the body and it has several functions that are critical at different stages of development.

My lab is continuing to define the role of APC in the nervous system. Our goal is to define changes caused by APC dysfunction that lead to learning deficits and autistic-like behaviors.

Hope this information clears up your questions.

My best regards to you and your daughter.

So why did I ask these questions? Well, its been my experience that the antivax crowd leap on any science that seems to have an outcome that is linked to autism, to either trash it or link vaccines to it. I’m hoping Dr Jacob’s answers lead away from the possibility of linking autism to vaccines via APC dysfunction.

Autism and learning disabilities connected to APC protein

25 Aug

‘What the hell does that mean?’ I hear you cry.

OK, so the way I understand it, APC is a protien which plays an important role in helping synapses grow properly. If synapses – which are the bits that transfer data from neuron to neuron – don’t grow properly then data doesn’t get passed properly. This particular protien – APC – is responsible for the synapse function for learning and memory.

In the in vivo study, the team blocked APC function and found that synaptic levels of the cell adhesion proteins neuroligin and neurexin dropped considerably. Without normal levels of these proteins, synapses were less mature both structurally and functionally. Mutations in the genes for neuroligin and neurexin are associated with autism in humans, but until now, little was known about the mechanisms responsible for localizing these proteins at the synapse. “Our laboratory study is the first to show that APC is needed to recruit neuroligin and neurexin to the synapse. This finding provides new insights into the mechanisms required for proper synapse function as well as molecular changes at the synapse that likely contribute to autistic behaviors and learning deficits in people with APC loss of function gene mutations,” said [lead author, Michele H. ] Jacob.

Source. Insert mine.

Right, so – again as I understand it – when the authors blocked APC function, they found that levels of the proteins neuroligin and neurexin dropped. So what…? Well, without these two proteins at normal levels, synapses grew improperly. So what…? Turns out that scientists already know that mutuations in the genes for neuroligin and neurexin are associated with autism. Aha.

Eli Lilly halts two clinical trials of an experimental Alzheimer’s treatment

19 Aug

This has been reported in a number of places, including the New York Times in their article Lilly Stops Alzheimer’s Drug Trials.

From the NY Times:

Eli Lilly halted two late-stage clinical trials of an experimental Alzheimer’s treatment on Tuesday, representing a setback to one leading theory on treating the degenerative disease and a new blow to Lilly’s business prospects.

One defining feature of Alzheimers disease is the presence of amyloid plaque in the brain. The now-halted clinical trial was for a drug which reduces this plaque.

The basic idea is fairly straightforward: if plaque is present in the brains of those with Alzheimer’s, removing the plaque may help reduce or reverse the symptoms. Instead, researchers were finding that the drug was making symptoms worse. Again from the times:

The company said patients who had taken the drug, intended to reduce plaque in the brain, actually showed worse cognitive functioning and less ability to perform daily living tasks than patients who had taken a placebo.

Why bring this up on an autism blog? Because this trial gives a good example of why I am very concerned about the use of untested therapies on autistics. It isn’t because of some objection to a “cure”. There is no existing autism cure. There is no autism cure proposed or in any stage of a clinical trial. While there is some very good and important discussions about any potential cure, it is for the present a hypothetical discussion. No, it isn’t the cure debate which drives me. It is safety. Plain and simple.

Consider autism therapies (both alternative and off-label) from a viewpoint of safety for the moment with the lessons learned from the Alzheimer’s trial.

Clinical trials are all about safety and efficacy. Is the therapy (drug) safe? Does it work? Before a clinical trial is even started, there has to be some reason to believe that the therapy would be safe and effective. Researchers have to ask the question, “what will this do?” In the Eli Lilly Alzheimer’s trial, they had reason to believe that the drug would reduce amyloid plaque. They had (I assume) some earlier trials to prove the drug reached some level of safety. With that in hand, Eli Lilly went forward to large-scale testing with people and they found that, at least for their test group (people with somewhat advanced Alzheimer’s disease), the drug was harmful.

From the NY Times story:

Lilly’s drug was intended to reduce production of so-called amyloid beta plaques in the brain by inhibiting the activity of an enzyme called gamma secretase.

Dr. Siemers of Lilly said the failed trials might indicate that too much reduction in amyloid beta unexpectedly harms cognitive functions, or it may be that the problems arose from the drug’s effect on some 20 other proteins.

Unintended and unforeseen consequences.

Consider alternative therapies being applied to autistics. For example, consider anti-inflammatory drugs. These are existing drugs used off-label, so some safety data are available. There is evidence of inflammation in the brains for some autistics, so why not treat it?

Because we don’t understand why there is inflammation in the brains of autistics. Because of that, we don’t know if there are any unintended consequences of anti-inflammatory therapies. From a story last year in the Chicago Tribune, this section discussing the team from Johns Hopkins/Kennedy Krieger which first published on neuroinflammation in autistics:

“THERE IS NO indication for using anti-inflammatory medications in patients with autism,” the [Johns Hopkins] team wrote.

Meddling with neuroinflammation could actually be a terrible mistake, said co-author Dr. Andrew Zimmerman, director of medical research at the Center for Autism and Related Disorders at the Kennedy Krieger Institute in Baltimore.

“It may actually be an attempt of the brain to repair itself,” said Zimmerman, a pediatric neurologist. Suppressing the immune response “could be doing harm.”

There are other classes of alternative therapies used in autism. Therapies which most likely are doing nothing beyond the placebo effect are in one class. For example, homeopathy. I don’t spend a lot of time writing about homeopathy. In fact, I don’t know if I have blogged about it at all. Even though it is bad science, it isn’t really dangerous. Another class of alternative therapies are those based in really bad science and which carry the potential of harm. Lupron comes readily to mind. Lupron therapy is based on two levels of very bad science. First, that autism is caused by mercury poisoning. Second, that reducing testosterone in the body will aid it in eliminating mercury. Lupron has been through clinical trials (not for autism) demostrating some level of safety, there are serious known side effects. Worse, the manner in which it is used in autistic children is very problematic–delaying puberty.

Back to the Alzheimer’s trial–I actually welcome the trial itself. I consider those who undertake clinical trials to be very brave individuals. I for one hope there are effective therapies for Alzheimer’s and other forms of dementia soon. It is a great fear for most, if not all, of us that we spend the last years of our lives with dementia. For the parent of a disabled child, this fear is only compounded. The thought of spending my last years draining resources I would rather leave to my child is one of the worst futures I can imagine.

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