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SafeMinds: why won’t you tell your membership about the vaccine safety study you funded? Perhaps because it says vaccines are safe?

28 Aug

Earlier this year a paper was published on vaccine safety: Examination of the Safety of Pediatric Vaccine Schedules in a Non-Human Primate Model: Assessments of Neurodevelopment, Learning, and Social Behavior. This was a followup study to earlier pilot studies that got a lot of attention in the “vaccines-cause-autism” groups (Delayed acquisition of neonatal reflexes in newborn primates receiving a thimerosal-containing hepatitis B vaccine: influence of gestational age and birth weight and Influence of pediatric vaccines on amygdala growth and opioid ligand binding in rhesus macaque infants: a pilot study.)

It is worth noting that the pilot studies didn’t link vaccines to autism. They did make claims that some early reflexes were delayed in the monkeys given thimerosal containing vaccines. If you see someone talking about “root” or “snout” or “suck” reflexes in a vaccine discussion, they are referring to the studies above. These were pilot studies–small preliminary studies to see if it is worth launching a larger study. As such the results should have been taken with caution. But caution is not what groups like SafeMinds (or any of the groups that promote the failed vaccine-autism link) are known for. Inflating any scrap of evidence that can support their political point of view, that’s what they are known for.

SafeMinds made a big deal out of the early studies. Mark Blaxill (then of SafeMinds) called the study a “blockbuster” in a four thousand word analysis. That’s a lot of space to devote considering the full study was eight thousand words. And, as noted already, preliminary. But politics is politics.

Now, an intellectually honest person, or group, would watch for the followup study and report on it no matter the result. Because, let’s face it, if you are going to spend 4000 words overstating the importance of a study, scaring people and instilling them with guilt and pain over their child’s disability, you have a responsibility to do a follow up.

If you are intellectually honest.

So, as noted above, the follow up study was published. It was published in April. Four months ago. And I don’t see anything from Mr. Blaxill on the Age of Autism blog (where he posted his “blockbuster” article) or at the SafeMinds website on the followup study. SafeMinds has their own blog, and if you search it for, say “snout”, you get this article (Ground-Breaking Monkey Study: Mercury-Containing Hepatitis B Vaccine Causes Brain Damage) on the pilot study, calling it “groundbreaking” and claiming that it demonstrates that the thimerosal containing HepB vaccine causes brain damage.

Very strong words. Words which, if overblown, are very damaging. Imagine going through life as a parent thinking that you agreed to a vaccine and that caused brain damage to your child. Now imagine that the evidence you used to draw that conclusion was (a) not strong to begin with and (b) now refuted.

Wouldn’t you want to know the truth? Wouldn’t you expect the people and the organizations that convinced you of this falshood to seek you out and correct their mistake?

And this is why people don’t hold Mr. Blaxill or SafeMinds in high regard. They are quick to scare but don’t have the courage to admit they were wrong. Courage isn’t standing up and saying unpopular truths. Courage is standing up and admitting that your “unpopular truth” was, in fact, not the truth at all.

Now, why pick on SafeMinds in specific here? A lot of people and groups jumped on the pilot study and spread a lot of fear. Check out the footnotes of the study.

This work was supported by the Ted Lindsay Foundation, SafeMinds, National Autism Association, the Vernick family, and the Johnson family

SafeMinds helped fund the new study. The one they are ignoring. They were likely aware of the results before they were published. But no word.

I expect more from decent advocacy organizations. But I am not surprised with SafeMinds, nor Mark Blaxill.

Yes, the National Autism Association did too and they need to step up as well (a point I hope to make in a later article).

How about the Johnson Family? Well, the Johnson Center stepped up and put out a press release New Research Finds No Evidence That Thimerosal-Containing Vaccines Affect Neurodevelopment and Behavior in Infant Primates. (all SafeMinds, the Age of Autism and the National Autism Association needs to do as a start is publish the press release).

Here’s the last sentence of the press release, quoting the lead researcher: “Despite these limitations, the data in this primate study overwhelmingly provides support for the safety of pediatric vaccines”

It would take a lot of courage for SafeMinds and Mark Blaxill to publicize such a statement. More than they have.


By Matt Carey

Was autism ever a first advocacy priority for those promoting the idea that vaccines cause autism?

2 Mar

Years back the evidence was rolling in debunking the hypotheses that the MMR and/or thimerosal in vaccines causes autism. At that time I naively wrote some colleagues in online writer’s community about how perhaps the groups that had been advocating about autism being a vaccine-induced epidemic would now become actual autism advocacy groups. They were at a fork in the road: become autism organizations or focus solely on vaccines. But acting like they were doing both was no longer going to work. One writer responded in a way that has stuck with me as he has been shown to be dead on right. Dr. David Gorski (who writes at Science Based Medicine among other places) was the colleague and I he said essentially: it has always been about the vaccines for them and it always will.

Years later it’s obvious: Dr. Gorski was correct. I was wrong. And we are seeing good examples of that now in this measles outbreak as groups like Safeminds and, of course, the Age of Autism blog chime in with articles downplaying the dangers of measles. A prime example recently came on AoA from Mark Blaxill. Mr. Blaxill is largely responsible for the thimerosal scare of the past decade. He wrote a paper (published in the non peer reviewed Medical Hypotheses) Thimerosal and autism? A plausible hypothesis that should not be dismissed. It was junk when it was published, it’s junk now.

His recent article on AoA is “Measles Hysteria — The Truth About a Non-Epidemic in Eight Simple Slides”. It’s junk and one could spend an article debunking each point. But Let’s take a more focused look. He has a slide “Why Measles is No Longer a Threat in the U.S.” (click to enlarge)

M Blaxill misinfo 1

So, it was supposedly 1500 infections ago that someone in the U.S. died of measles. Only 1 in 1500 or so and so it’s not a big deal. Mr. Blaxill even called (or got someone from his organization to call) the CDC for a statement. Who knows what was asked, what was said. Maybe the CDC spokesperson made a mistake. You see, Dr. Vincent Iannelli at Pediatrics.About.Com actually tabulated measles deaths in the U.S. in recent years. Even with a low infection rate, people die of measles and have died in the U.S.. After presenting the data for each year he summarizes:

So that’s 10 measles deaths since 2000 and at least 7 measles deaths since 2005.

Why do people say that there have been no measles deaths in the United States in the past 10 years? Whether they are misinformed or intentionally trying to misinform people, they are wrong.

One can confirm this on the CDC Wonder website. Here’s a screenshot.

This isn’t about proving Mark Blaxill wrong on some point. Because in the end it doesn’t matter if it’s one death or ten deaths, it’s too many. But I suspect 1 death or 10 deaths wouldn’t change Mr. Blaxill’s assertion that measles is a minor deasease.

\Those 10 measles deaths Dr. Iannelli mentions are deaths that occur during the infection, usually from complications like pneumonia or encephalitis. But the thing about measles is that it can kill years later. There’s a condition called SSPE, Subacute Sclerosing Panencephalitis. You see, for some people, the measles virus enters the brain and stays there. And slowly kills.

From Dr. Iannelli:

About 6 to 8 years after having measles, children with SSPE develop progressive neurological symptoms, including memory loss, behavior changes, uncontrollable movements, and even seizures. As symptoms progress, they may become blind, develop stiff muscles, become unable to walk, and eventually deteriorate to a persistent vegetative state.

Children with SSPE usually die within 1 to 3 years of first developing symptoms

and

That’s 32 SSPE deaths since 2000 and at least 19 SSPE deaths since 2005. Why so many? Many of them can likely be attributed to the large number of cases associated with measles outbreaks from 1989 to 1991.

There is no cure for measles infection. There is no cure for SSPE. One can read more about SSPE at the link given above or at a recent article at Science Based Medicine: SSPE: A Deadly and Not-That-Rare Complication of Measles.

Mr. Blaxill includes a quote from someone in the 1963 who stated that measles is of “moderate severity” or “low fatality”. Perhaps to someone who lived through the early 20th century when measles was even more deadly, this might seem so. Perhaps. But not now. And how can someone ever use the phrase “self limiting” about a disease that can lead to SSPE? SSPE is only “self limiting” in the death of the patient.

Another of Mr. Blaxill’s slides shows the decline in measles infections and deaths following the introduction of the vaccine. Mr. Blaxill annotated this with his own observations (click to enlarge):

M Blaxill misinfo 2

Here’s the thing that pops out of that graph: the death rate has remained constant at about 1 in 1,000 since at least 1950. Take a look at any datapoint in the deaths and go up a factor of 1,000 and there’s the infection rate. And that doesn’t account for SSPE deaths years later.

Over the years I’ve found that Mr. Blaxill often takes an unreasonable and unfounded stance on issues. But since when is a death rate of 1 in 1,000 low enough to state “Why Measles is No Longer a Threat in the U.S.”?

For comparison, Mr. Blaxill informs us that there have been 80 deaths attributed to measles containing vaccines reported to VAERS (the Vaccine Adverse Event Reporting System) in the past 10 years. He ignores, as most people do who use VAERS in this manner, to include the disclaimer one must acknowledge in order to access VAERS data, which concludes that VAERS data do not imply causality. But let’s for the moment assume that every report to VAERS is causal. 80 deaths. There are about 4 million babies born in the U.S. each year. About 90% get the MMR vaccine. Twice. Over 10 years. That’s nearly 80 million doses of MMR vaccine administered. So, even if we take each report to VAERS as causal, that would be 1 death in 1 million doses. 1 death in 500,000 infants. This is a huge over estimate given the assumptions, but let’s do the difficult: compare these numbers. To Mr. Blaxill 1 in 500,000 is too many, but 1 in 1,500 is “low fatality”.

Even using the Mr. Blaxill’s flawed assumptions, his logic doesn’t make any sense.

Let’s take a look at Mr. Blaxill’s concluding slide so I can bring this back to how it shows that he has abandoned not just logic but also the autism community. I’ve highlighted one sentence that is particularly important. (click to enlarge):

M Blaxill misinfo 3

Measles has ceased to be a dangerous illness? Seriously? First, the idea that we can accept 1 out of 1000 people dying due to measles is just astonishingly bad advocacy. For that point alone we in the autism community need to distance ourselves from Mr. Blaxill and people like him. These irresponsible actions are not the actions of the autism community.

That said, let’s consider this key phrase: “in healthy children”. If you will, try to recall back in the day when Mr. Blaxill presented himself as an autism advocate. Actually, we don’t even have to go back that far, only recently he was telling a congressional hearing:

In New Jersey, 1 in 29 boys born in 2000 were diagnosed autistic.

What’s going on? Why are so many American children sick?

The message he had for many years was that autistic children are sick. Not healthy. His former organization (Safeminds) would be quick to point out a number of conditions that are more common in autistics than in the general population. Since even by his own definition autistics are not “healthy”, why should we let measles return in force to the U.S.? Of course it is Mr. Blaxill’s failed hypothesis that vaccines are making children “sick”. But let’s consider this very real point: the developmentally disabled are more likely to become sickened by infectious diseases and they are more likely to die (Why vaccination uptake matters to the autism community).

And that’s ignoring the fact that a large fraction of autistics are also epileptic. And a huge trigger for seizures is infectious disease and the prolonged fever that comes with it. Perhaps Mr. Blaxill is unaware of the term status epilepticus, the situation where someone gets into a state of constant seizures. And, yes, this can be brought on by infection.

Or perhaps Mr. Blaxill has forgotten the emphasis his community placed on mitochondrial disease and autism just a few short years ago.

From a U.C. San Diego Metabolic Deseaese Center website, the paragraph: What is Mitochondrial Disease?

If a child is stricken with a catastrophic disease affecting three or more organ systems, or if a child has been afflicted with a relapsing disease that affects two or more organ systems and leads to slow but measurable deterioration, he or she may have a mitochondrial disease. At times, mitochondrial diseases can cause isolated symptoms. These may include unexplained seizures, low blood counts, dystonia (abnormal muscle tone or spasms), blindness, deafness, dementia, ataxia (stumbling or tremors), cerebral palsy, heart failure, or progressive muscle weakness. More often, however, several organ systems are affected in sequence, one faltering or failing after another. Good periods are frequently punctuated by abrupt deteriorations that are caused by simple infections. For children with mitochondrial disease these infections can be life threatening, and leave them with deficits that cannot be recovered.

Emphasis added. Some fraction of our population does have mitochondrial disease. Allowing diseases like measles back would put this community (as well as those with mitochondrial disease without autism) at huge risk.

I’d like to say that Mr. Blaxill, like many in the “autism is a vaccine-induced epidemic” camp, has lost his way. A very valid question is whether Mr. Blaxill and his colleagues were ever on the path of autism advocacy. Was it always, as Dr. Gorski opined, about the vaccines?

While I’ve entitled this article “Was autism ever a first advocacy priority for those promoting the idea that vaccines cause autism?”, in the end motivations are secondary. Mr. Blaxill’s actions are and have been irresponsible. They are an example of the actions of a group of faux autism advocates that have a history of irresponsible actions. Not just to public health but to the autism communities.


By Matt Carey

Is Autism Speaks supporting vaccine-autism causation proponent Congressman Bill Posey?

19 Aug

Someone forwarded an email from the “Autism Action Network” recently. The email asked people to support Congressman Bill Posey’s election campaign by attending a fundraiser. Looks like a few big donors to Mr. Posey were going to attend, including Sallie Bernard of SafeMinds and Autism Speaks. Ms. Bernard certainly is with both organizations, but I wonder if she was attending as an Autism Speaks officer or if Autism Speaks was even aware that their name was being used to promote the fundraiser.

Perhaps Ms. Bernard wasn’t aware that her Autism Speaks affiliation was being used this way. I’ve seen some of my affiliations used where I didn’t expect nor want them. Perhaps Ms. Bernard was aware that the AS affiliation was being used in this advertisement, but Autism Speaks wasn’t. Perhaps Autism Speaks was aware and supported this effort. I’m not betting heavily on that last option though.

Here’s the list of donors for the fundraiser in the email I got:

Jennifer Larson of the Canary Party and Health Freedom
Sallie Bernard of Safeminds and Autism Speaks
JB Handley of Generation Rescue
Tony Lyons of Shy[sic] Horse Publishing
Barry Segal of Focus Autism
Mark Blaxill of the Canary Party and Health Freedom
Dr. Gary Kompothecras
Teri Costigan

The Autism Speaks name adds a legitimacy to this fundraiser that the other groups just can’t. The Canary Party and Health Freedom (which I assume to be Americans for Health Choice) are basically the same people with “Canary Party” as a political party and “heath freedom” as a charity. The Canary Party/Health Freedom team is led by the same people who funded large donations to Oversight & Government Reform Committee Chair Daryl Issa ($40k plus). JB Handley is not as vocal as he once was, but he founded Generation Rescue on the notion that “autism is just a misdiagnosis for mercury poisoning“. Sky Horse publishing is boutique publisher of many of the books on vaccines and autism, including “Age of Autism” and books by Andrew Wakefield. Barry Segal (Focus Autism) has been a large supporter of groups like Generation Rescue, the Age of Autism, SafeMinds and is very vocal on his belief that vaccines cause not only autism, but many other health problems as well. Gary Kompothecras has been funding Mr. Posey for years and is an autism parent and benefactor of groups promoting the vaccine/autism idea.

Without Autism Speaks’ name added to this, this would be very clearly all about a small but wealthy group of people pushing the failed ideas of vaccines and autism. People with failed and damaging ideas have the right to lobby members of congress along with everyone else. I, for one, am glad that the vast majority of Congress has moved on from the vaccine/autism-epidemic idea. I look forward to the day when that majority reaches 100%.


By Matt Carey

And yet another vaccinated/unvaccinated comparison study, this time funded by SafeMinds

13 Aug

A study comparing vaccinated and unvaccinated children is expected to be published soon. That study was mentioned at a meeting of the Interagency Autism Coordinating Commitee earlier this year. With that announcement one might reasonably expect much discussion in the online autism parent community. Instead I’ve seen only one response: SafeMinds (an organization focused on the failed idea that mercury in vaccines caused the rise in autism diagnoses) put an article on their website noting that they were “worried” by this study (a response I already discussed). Perhaps I missed it, but I did not see a statement in the SafeMinds article that they have their own vaccinated/unvaccinated study ongoing. Not only a vaccinated/unvaccinated study, but one which parallels the one about to be published. Both the about to be published study and the SafeMinds funded study focus on baby siblings of autistic kids. Parents of autistic children are more likely to delay or forgo vaccines than are other parents. Also, the risk of autism is high in the baby sibling population, giving a ” ‘window of opportunity’ to observe any potential interactions between vaccinations and the diagnosis of ASD”, as SafeMinds put it. But read for yourself. Under “Recently Funded SafeMinds Investigations“, SafeMinds lists:

The Early Identification of Infants and Toddlers at Risk for Autism Spectrum Disorders, Developmental Delay and Developmental Language Disorders
CAROLE SAMANGO SPROUSE, ED.D., THE FOCUS FOUNDATION
The siblings of children with Autism Spectrum Disorder have a 90% incidence of speech and language delay and an 11% increased risk for Autism Spectrum Disorder (ASD). This proposal hypothesizes that the siblings who are not vaccinated will have a smaller incidence of ASD than the 11% already projected, as well as other developmental differences. The incidence of ASD in siblings will be lower in the unvaccinated population than vaccinated. The siblings of children with ASD provide a fertile ground to follow the neurodevelopmental progression of an at-risk population, and the effects of vaccinations on development. The siblings also provide a “window of opportunity” to observe any potential interactions between vaccinations and the diagnosis of ASD. It is very common for parents of children ASD to avoid vaccinating siblings in the first five years of life. This provides an interesting opportunity to observe and see possible correlations between vaccinations and ASD.

First, let me note the wording of that webpage: “Recently Funded SafeMinds Investigations”. Not Investigations Recently Funded by SafeMinds. Their choice of word order is poor. It implies that these are “SafeMinds Investigations” and not really independent. I will note that SafeMinds were more careful at the top of that page in how they framed the projects they have funded, but still, I would change the “SafeMinds Investigations” if I were they.

When I searched for information on the principle investigator for the SafeMinds study, I found a 2007 announcement for the study: Vaccinated/Unvaccinated Autism Baby Sibling Study, Carole Samango Sprouse, Ed.D., The Focus Foundation. Research does take time, something I wish SafeMinds made more clear in their public statements. It’s been seven years, though, and I haven’t seen this vaccinated/unvaccinated study published. The only payment I’ve seen in the SafeMinds tax forms to support this project was relatively small, $24,250 in 2006, so perhaps it wasn’t well enough supported to complete. Perhaps I missed the other support.

The principle investigator on the SafeMinds funded study has published a different study on autism and vaccines: Survey of Vaccine Beliefs and Practices Among Families Affected by Autism Spectrum Disorders, and remains active in disability research.

When we consider the question of studies comparing vaccinated/unvaccinated populations, there are at least 4 in various stages. Four. That, plus the number of statements one can find online calling for such a study and we see a very strong interest in this type of study.

Here are those four studies:

1) The self-named “National Vaccine Information Center” is funding a project at George Mason University. I believe this is being performed by a member of the NVIC.

2) Generation Rescue (and others) are funding a project at Jackson State University.

3) The SafeMinds funded study noted above.

and

4) the study about to be published.

Again, with this high level of interest, where was the response to the announcement that a vaccinated/unvaccinated study is nearing publication?


ByMatt Carey

Environmental risk factor related research funded by the NIH in 2014

18 Jul

There is a great interest from some in the autism parent community for environmental risk factor research. There is also a belief that this work is not being performed. While the amount of environmental risk factor research is less than the IACC has advised be performed (a point I made in my first IACC meeting), the amount of attention to environmental risk factors has been increasing.

Given this, I thought it would be interesting to see what projects and how many have been funded by the NIH this year (I believe they work on a fiscal year ending Sept. 30, so we have much but not all of the 2014 information available). I used the NIH Reporter website and did a very unscientific search for autism and environment, autism and risk and similar searches.

Below are the funded projects I’ve found. Some are directly on topic. Some more peripherally. And I know I’ve left some out (some on purpose–like Zebrafish studies–and some I missed). I think there are 33 projects below. Something like $20M. Keep in mind, not all Federally funded autism research goes through the NIH and not all autism research is Federally funded.

As I like to point out in these articles, you won’t find this information on the websites of the autism organizations which claim to be focused on environmental risk factor research. In fact, you are more likely to find statements that there is no such research ongoing or it is being blocked.

Here’s a quote from Sallie Bernard of SafeMinds, a quote that was repeated by Congressman Posey at a hearing held last year on autism:

“By ignoring the environmental component to autism, the government and scientific community have made a massive strategic error, wasting enormous amounts of money and time in mostly fruitless genetics-only research that has not helped us stop new cases of autism or helped people living with severe autism”

I think one can argue that more investment should be made. But “ignoring”? I realize that very few people will go to NIH Reporter and search for these projects. But I expect accuracy from those claiming to lead the autism community and acting as though they know the research landscape on autism and the environment.

I was going to ignore the “fruitless” comment above, but I just can’t. I sat on the subgroup writing the IACC’s updates on risk factor research in the Strategic Plan (question 3). As part of that I had the honor of working with some excellent researchers, both on the genetics and the environmental side. If I may be so bold as to relate what I heard in those discussions: I never heard these researchers claim that the genetics research was “fruitless”. Quite the opposite. Was there a strong sense that environmental risk factor research could be better funded? That was certainly my take away. And I agree. My predecessors on the IACC wrote a Plan that called for more research in this area.

That said, I am reminded of my favorite old saying

There’s more politics in science than science in politics.

Except quite frankly, I don’t think the message that environmental risk factor research is being “ignored” and “fruitless” has anything to do with science. It’s just politics.

Here’s that list of funded research (in no particular order):

POPULATION-BASED AUTISM GENETICS & ENVIRONMENT STUDY $655,813

PROSPECTIVE EVALUATION OF AIR POLLUTION, COGNITION, AND AUTISM FROM BIRTH ONWARD $545,679

PESTICIDE EXPOSURE AND CHILDHOOD AUTISM $184,503

PRENATAL TIMING OF HEAVY METAL EXPOSURES FROM AUTISTIC AND NON-AUTISTIC CHILDREN $231,692

MD CADDRE: STUDY TO EXPLORE EARLY DEVELOPMENT, SEED PHASE II $91,706

ANTECEDANTS SEQUELAE OF CHILDHOOD ONSET DISEASE $432,000

MITOCHONDRIAL DYSFUNCTION DUE TO ABERRANT MTOR-REGULATED MITOPHAGY IN AUTISM $183,568

PRENATAL AND NEONATAL BIOLOGIC MARKERS FOR AUTISM $784,863

AUTISM RISK, PRENATAL ENVIRONMENTAL EXPOSURES, AND PATHOPHYSIOLOGIC MARKERS $1,793,611

THE ROLES OF ENVIRONMENTAL RISKS AND GEX IN INCREASING ASD PREVALENCE $537,756

METHYLOMIC AND GENOMIC IMPACTS OF ORGANIC POLLUTANTS IN DUP15Q SYNDROME $341,921

EPIDEMIOLOGICAL RESEARCH ON AUTISM IN JAMAICA – PHASE II $564,795

EARLY PREGNANCY STRESS PROGRAMMING OF OFFSPRING EMOTIONALITY $396,000

GENOME-WIDE IDENTIFICATION OF VARIANTS AFFECTING EARLY HUMAN BRAIN DEVELOPMENT $413,630

EPIGENETIC AND TRANSCRIPTIONAL DYSREGULATION IN AUTISM SPECTRUM DISORDER $531,208

EPIGENETIC INFLUENCE ON THYROID HORMONE ACTION IN THE BRAIN AND ON BEHAVIOR $391,250

MATERNAL ADVERSITY AND EPIGENETIC AND BEHAVIORAL PROGRAMMING ACROSS GENERATIONS $583,246

EXPLORING INTERACTIONS BETWEEN FOLATE AND ENVIRONMENTAL RISK FACTORS FOR AUTISM $118,717

MD CADDRE: STUDY TO EXPLORE EARLY DEVELOPMENT, SEED PHASE II $1,600,000

CALIFORNIA CADDRE-SEED PHASE II $1,100,000

NC CADDRE: STUDY TO EXPLORE EARLY DEVELOPMENT (SEED) PHASE II $1,100,000

COLORADO CADDRE STUDY TO EXPLORE EARLY DEVELOPMENT CADDRE_SEED II $1,100,000

PA-CADDRE: STUDY TO EXPLORE EARLY DEVELOPMENT (SEED) PHASE II $1,100,000

SEX-DEPENDENT MICROGLIAL COLONIZATION AND VULNERABILITY TO A NEONATAL INFECTION $272,270

PRENATAL SEX STEROIDS, BISPHENOL A, PHTHALATES, AND SEXUALLY DIMORPHIC BEHAVIORS $244,996

ENVIRONMENT, IMPRINTING, AND NEURODEVELOPMENT $799,726

IN UTERO ANTIDEPRESSANT EXPOSURES AND RISK FOR AUTISM $348,000

SEX DIFFERENCES IN DEVELOPING MICROGLIA: IMPLICATIONS FOR SYNAPTIC PRUNING $392,500

ARE ENDOCRINE DISRUPTING COMPOUNDS ENVIRONMENTAL RISK FACTORS FOR AUTISM? $237,750

THE EFFECT OF MATERNAL OBESITY AND INFLAMMATION ON NEURONAL AND MICROGLIAL FUNCTI $78,250

TRANSCRIPTIONAL AND EPIGENETIC SIGNATURES OF HUMAN BRAIN DEVELOPMENT AND AUTISM $1,542,279

PROJECT 2: THE IMPACT OF ASSISTED REPRODUCTIVE TECHNOLOGIES ON THE LONG-TERM EPI $266,000

PRENATAL FACTORS AND RISK OF AUTISM IN A FINNISH NATIONAL BIRTH COHORT $579,293

One last note: I don’t see funding for the EARLI network. That strikes me as a shame.


By Matt Carey

Note: I serve as a public member to the IACC but all statements are my own.

Why won’t the government fund vaccine/autism research?

15 Jul

This question gets brought up a lot by some parent advocates. The are informed by groups promoting the idea of vaccine causation that the government is blocking this work. The evidence points strongly away from vaccines as a primary cause of autism, and investment in this area doesn’t seem wise. At least that’s the viewpoint of the majority of parents (including myself), autistics and researchers. But some remain unconvinced and want vaccine/autism research performed. And they are upset that none of this work is being performed.

Here’s a different question: why are the groups who promote the idea that vaccines cause autism failing to inform their members that, yes, indeed vaccine/autism research is being performed?

Or, to put it simply: vaccine/autism research is being performed and it’s being funded by the government. But you wouldn’t know that if you read, say, the Age of Autism blog, Generation Rescue’s website, SafeMinds’ website, or the other groups advocating for this research. If you are interested in vaccine/autism research and you are reading about these projects for the first time here, ask yourself “why have these orgs not informed me of this?”.

As noted here recently, Tom Insel discussed an upcoming vaccine/autism study. Already commissioned, performed and in the publication stage. That announcement was in April. What was the response from the community that has pleaded for vaccine/autism research? For the first few months: Silence. In July, SafeMinds finally put out an article showing that they were “worried” about this study. I don’t see much discussion of this announcement from other groups or outlets.

I’m not surprised by this. I’ve noted before that work on areas such as vaccines, mercury, environmental risk factor research and GI dysfunction don’t get discussed by the groups that are focused on these topics. I’ve covered the research in these areas more than they have.

So let’s get back to what other work is going on in vaccines and autism. Let’s start with the simple question: how would you find out? One place is the IACC/OARC Autism Spectrum Disorder Research Portfolio Analysis Web Tool. That could use updating, but it is an easily searchable database. Another place is NIH Reporter. It’s less easy to use than the Portfolio Analysis Tool and includes all of NIH. I.e. it covers non autism topics and doesn’t include projects being done outside of NIH (say, by Autism Speaks or other private funders). But, search Reporter for autism and vaccines or mercury and what do you get? Quite a number hits. Let’s consider a few.

How about:

There’s a study by Ian Lipkin’s group at Columbia titled: GENE-ENVIRONMENT INTERACTIONS IN AN AUTISM BIRTH COHORT.

There’s a study by Gene Sackett’s group, A PRIMATE MODEL OF GUT, IMMUNE, AND CNS RESPONSE TO CHILDHOOD VACCINES. This appears to be a follow on project to the Laura Hewitson studies that were discussed a great deal online a few years ago.

Isaac Pessah’s group at the UC Davis MIND Institute has a project NEURODEVELOPMENTAL TOXICOLOGY OF AUTISM. Prof. Pessah also had a multiyear project ENVIROMENTAL FACTORS IN THE ETIOLOGY OF AUTISM

Judy Van de Water’s group at UC Davis MIND Institute has a project IMMUNOLOGICAL SUSCEPTIBILITY OF AUTISM.

The Lewin Group study (which I believe is the one mentioned by Tom Insel) STUDY OF HEALTH OUTCOMES IN CHILDREN WITH AUTISM AND THEIR FAMILIES. (Just a note–see how this has been publicly available information for a year?)

There’s the CHARGE study, which is looking at a large array of potential environmental risk factors, including specifically mentioning mercury. THE CHARGE STUDY: CHILDHOOD AUTISM RISKS FROM GENETICS AND THE ENVIRONMENT

Here’s a 2014 grant to Ray Palmer, well known to the groups promoting mercury as a cause of autism, PRENATAL TIMING OF HEAVY METAL EXPOSURES FROM AUTISTIC AND NON-AUTISTIC CHILDREN.

The EPIDEMIOLOGICAL RESEARCH ON AUTISM IN JAMAICA – PHASE II project is continuing (hence the Phase II) and includes work on mercury.

There are more projects. Some I left out because they are older. But I think the point is made and is very clear: vaccine/autism and mercury/autism research are being funded.

And that is without even discussing how research on the biology of autism feeds into all etiological questions. Whether it’s vaccine, genetics or what have you, if you understand the biology, you have a better chance of understanding the cause. (when I searched NIH Reporter with the terms Autism and Immune, I got 25 pages of hits. Sure, not all are on-topic, but that’s 25 pages, 606 topics).

Here are the full abstracts–with emphasis added by me–for the NIH Reporter projects mentioned above.

GENE-ENVIRONMENT INTERACTIONS IN AN AUTISM BIRTH COHORT.

Abstract Text:
Reports of increasing prevalence of autism spectrum disorders (ASDs), a set of highly genetic conditions, are intensifying interest in the role of environmental exposures, including infectious, immune, and toxic factors. Retrospective studies exploring associations between environmental factors and ASDs are compromised by selection bias, small sample sizes, possibly invalid diagnosis, and absence of biologic measures. This prospective study will employ an unselected birth cohort of 75,500 in which cases are ascertained through screening of the entire population, diagnoses established using uniform procedures, extensive histories and clinical data obtained, and biologic samples collected serially throughout pregnancy and early childhood. The application of high throughput laboratory assays to derive maximal information from developmentally-influenced, finite, and nonrenewable biologic samples, and inclusion of early screening and diagnostic assessments, will permit an unprecedented, rich view of the longitudinal trajectory and nascent signs and symptoms of ASDs, facilitate discovery of biomarkers, and afford unique insights into the role of gene:environment interactions in ASD pathogenesis. Specific aims are to: (1) establish the autism Birth Cohort (ABC) through ascertainment of cases of autism spectrum disorder (ASD, N=150-233) and selection of controls (N-1000) from the Norway Mothers and Child (MoBa) cohort; (2) examine biologic pathways that may predispose to ASD, through evaluation of immune, endocrine, and neuroregulatory factors in mothers during early gestation or at birth and in children, at birth or 30 months postnatal; (3) identify environmental factors that may be directly or indirectly associated with ASD, including pre- or postnatal infection, vaccination, very low birth weight or other obstetric risk factors in which infections are implicated, dietary and/or environmental exposure to methylmercury; (4) describe the natural history of clinical, anthropometric, and neurobehavioral features of ASD; and (5) explore genotypic influences that may be directly or indirectly associated with ASD by testing associations of ASD and/or its endophenotypes with family history of autoimmune disease or selected candidate genes, and investigating conditional gene-environment effects using antecedent factors found to influence ASD risk.

NIH Spending Category:
autism; Brain Disorders; Clinical Research; Genetics; Immunization; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Neurosciences; Pediatric; Prevention; vaccine Related

Project Terms:
autism spectrum disorder; Autistic Disorder; Autoimmune Diseases; base; Biological Assay; Biological Markers; Birth; Candidate Disease Gene; case control; Child; Clinical; Clinical Data; cohort; Cohort Studies; Collaborations; Collection; Confusion; Control Groups; design; Development; Diagnosis; Diagnostic; Discipline of obstetrics; Disease; disorder risk; Drops; early childhood; Endocrine; endophenotype; Environment; Environmental Exposure; Environmental Risk Factor; Epidemic; Epidemiologic Studies; Evaluation; Exposure to; Family history of; gene environment interaction; Genes; Genetic; Hereditary Disease; Immune; immune function; Infection; insight; interest; Investigation; Laboratories; Life; Measles; Measures; member; Mercury; Methylmercury Compounds; Mothers; Mumps; Natural History; Nested Case-Control Study; neurobehavioral; Neurodevelopmental Disorder; Norway; novel; Pathogenesis; Pathway interactions; Phase; Population; postnatal; Pregnancy; prenatal; Prevalence; Procedures; prospective; Prospective Studies; Recording of previous events; Relative (related person); Reporting; Research; Research Design; Retrospective Studies; Risk Factors; Role; Rubella; Sample Size; Sampling; Screening procedure; Selection Bias; Signs and Symptoms; Specimen; Testing; Vaccination; Vaccines; Vacuum; Very Low Birth Weight Infant

A PRIMATE MODEL OF GUT, IMMUNE, AND CNS RESPONSE TO CHILDHOOD VACCINES.

Abstract Text:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject’s principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Diagnoses of childhood developmental disorders involving autism-spectrum symptoms are increasing, estimated to affect 1 in 100 children in the United States. Childhood Vaccines have been hypothesized to be contributory factors to this increase. The childhood vaccine regimen has an experimentally unstudied potential for cumulative and synergistic toxicities and possible immunologic interference to normal development. A prior study developed a primate model to assess neurodevelopmental consequences of the 1994-1999 pediatric thimerosal vaccine regimen (1994-1999). Significant neurodevelopmental deficits were evident for vaccinated animals in survival reflexes and standardized cognitive tests, and exposed animals developed gastrointestinal inflammation associated with focal transmural colitis, lymphoid hyperplasia, and syncytia.

NIH Spending Category:
autism; Brain Disorders; Cancer; Digestive Diseases; Immunization; Lymphoma; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Pediatric; Rare Diseases; vaccine Related

Project Terms:
Affect; Animals; Autistic Disorder; Child; Childhood; Cognitive; Colitis; cost; Development; developmental disease/disorder; Diagnosis; Funding; gastrointestinal; Giant Cells; Grant; Immune; Immunologics; Inflammation; lymphoid hyperplasia; Modeling; National Center for Research Resources; Neurodevelopmental Deficit; Primates; Principal Investigator; Reflex action; Regimen; Research; Research Infrastructure; Resources; response; Source; Symptoms; Testing; Thimerosal; Toxic effect; United States; United States National Institutes of Health; Vaccinated; Vaccines

NEURODEVELOPMENTAL TOXICOLOGY OF AUTISM

Abstract Text:
The long range goal is to determine if exposure to environmental toxicants early in development contributes to the etiology of neurodevelopmental disorders such as autism. A related goal is to determine whether susceptibility to autoimmune disease increases the neurotoxicity of environmental contaminants and increases the risk for developing disorders such as autism. Understanding how exposure to environmental toxicants may contribute to the etiology of neurodevelopmental disorders is important so that the exposure risks can be identified and minimized. If immune system dysfunction is found to increase the risk of exposure to environmental toxicants, then exposure limits to toxic substances can be lowered, and children with immune system dysfunction who may be at increase risk can be identified and protected. The specific aims are to expose mouse strains with low (C57BL/6J) or high (SJL mice) susceptibility to autoimmunity perinatally to either methylmercury (MeHg), polychlorinated biphenyl 95 (PCB 95) or polybrominated diphenyl ether 47 (BDE 47). We will then compare the effects of toxicant exposure between these mouse strains on brain development, complex social behaviors, and immune system function. The hypothesis is that perinatal exposure to each of these toxic substances will impair brain development and behavior, and that suscepbility to autoimmune disease will increase the neuro- and immunotoxicity of these agents. We will also explore a potentially new model of autism in mice injected prenatally with unique autoantibodies isolated from the serum of mothers who have given birth to two more more autistic children. Brain development will be examined histologically using stereological procedures and immunohistochemistry. Complex social behaviors will be studied using behavioral testing procedures established in our laboratory that measure social recognition, social interaction and social communication in mice. Immune system status will be established by measuring cytokines, chemokines, immunoglobulins, and quantifying immune system response to antigenic stimulation. In addition, seizure susceptibility will be measured in toxicant-exposed mice as well as measures of synaptic excitibility and plasticity in hippocampal brain slices. These studies will provide critical new information on the role of the immune system and its interaction with environmental contaminants in autism and other neurodevelopmental disorders.

NIH Spending Category:
autism; Autoimmune Disease; Behavioral and Social Science; Brain Disorders; Epilepsy; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Neurodegenerative; Neurosciences; Pediatric; Perinatal Period – Conditions Originating in Perinatal Period

Project Terms:
Age; Animal Testing; Antibodies; Anxiety; autistic Children; Autistic Disorder; Autoantibodies; Autoimmune Diseases; Autoimmune Process; Autoimmunity; Behavior; behavior test; Behavioral; Biological Assay; Birth; Brain; CCL2 gene; CCL3 gene; CCL4 gene; Cerebellum; chemokine; Chemokine (C-C Motif) Ligand 4; Child; Complex; cytokine; density; Development; developmental disease/disorder; developmental neurotoxicity; Disease; Environmental Pollution; Enzyme-Linked Immunosorbent Assay; Etiology; Exposure to; fetal; Fibroblast Growth Factor; Flurothyl; Fright; Glutamate Receptor; Goals; Granulocyte-Macrophage Colony-Stimulating Factor; Hippocampus (Brain); Histologic; Homer 1; human TNF protein; IL8 gene; Immune response; Immune system; Immune System and Related Disorders; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Immunohistochemistry; Immunophilins; immunotoxicity; In Vitro; in vivo; Infection; Interferon Type II; Interleukin-10; Interleukin-17; Interleukin-4; Interleukin-5; Interleukin-6; Kindling (Neurology); Laboratories; Learning; Leptin; link protein; Long-Term Potentiation; Measures; Memory; Metabotropic Glutamate Receptors; Methods; Methylmercury Compounds; Mitogens; Modeling; Mothers; mouse model; Mouse Strains; Mus; N-Methylaspartate; neurobehavioral disorder; neurodevelopment; Neurodevelopmental Disorder; Neurologic; Neuronal Injury; Neurons; neurotoxicity; offspring; Pentylenetetrazole; Perinatal; Perinatal Exposure; phenyl ether; Plasma; Poisons; Polychlorinated Biphenyls; postnatal; Predisposition; pregnant; prenatal; prenatal exposure; Preparation; Principal Investigator; Procedures; programs; Proteins; RANTES; receptor; receptor function; repaired; Research Design; Research Personnel; research study; response; Risk; Role; Ryanodine Receptor Calcium Release Channel; Ryanodine Receptors; Seizures; sensory gating; Sensory Motor Performances; Serological; Serum; Signal Pathway; Signal Transduction; SJL Mouse; SJL/J Mouse; Slice; Small Inducible Cytokine A3; social; Social Behavior; social communication; Social Interaction; Source; Splenocyte; Structure; Synapses; synaptotagmin; System; T-Cell Proliferation; Testing; Tetanus; Tetanus Toxoid; Tetanus vaccine; Toxic Environmental Substances; toxicant; Toxicant exposure; Toxicology; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factors; Western Blotting; Work; Xenobiotics

IMMUNOLOGICAL SUSCEPTIBILITY OF AUTISM.
Abstract Text:
Recent studies indicate that immune function in children with autism spectrum disorder (ASD) is profoundly altered compared to developmentally healthy controls. There is a strong interface between the immune system and the neurologic network, and successful neurodevelopment is contingent upon a successful interaction between these two systems. We have identified several aspects of immune dysfunction in patients with autism compared with typically developing controls. These include a reduced response to vaccine antigens of bacterial origin, altered cytokine levels in plasma and upon stimulation of PBMC, increased levels of leptin in patients with early onset autism, and autoantibodies to brain antigens. This wide and complex variety of immune anomalies noted in our first funding period is in keeping with the broad range of phenotypes encompassed by the autism spectrum. Thus, we will build upon our earlier findings of both serologic and cellular changes in immune function. While our studies in the previous project period were aimed at a broad analysis of immune function in patients with autism, the current proposal will address the mechanisms responsible for the numerous alterations in immune homeostasis uncovered in our earlier studies. Therefore, our primary focus will be on the mechanisms responsible for such anomalies in immune function through an in depth analysis of cellular immune function. Our overall hypothesis is that patients with autism have a fundamental defect at the cellular level that ultimately leads to abnormalities in immune function and heightened susceptibility to environmental triggers. To examine this, we propose to: (1) examine longitudinally the serologic profile of children with ASD to ascertain whether the various immune changes noted in our first studies are maintained and/or deteriorating further; (2) determine which immune cell population(s) plays a critical role in the immune dysfunction seen in patients with autism; and (3) fully characterize the autoantibody response in a subpopulation of children with ASD and some mothers of children with ASD. It must be noted that due to the highly heterogeneous nature of autism, there will potentially be immunologic differences that relate to sub-groups of patients with autism. Therefore, we will carefully define the study groups based on our current data to include children with early onset autism, children with delayed onset/regressive autism, general population controls, and children with developmental disorders without ASD. The studies will be performed on CHARGE subjects formerly analyzed by our laboratory (CHARGE-BACK study). This will allow us to extend our prior studies longitudinally to determine if the immune dysregulation, such as increased leptin levels in the early onset patients, remains over time. The following aims address both the serologic and cellular aspects of immune function in patients with autism.

NIH Spending Category:
autism; Brain Disorders; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Neurosciences; Pediatric

Project Terms:
Address; Age; anti-IgM; Antibodies; Antigens; autism spectrum disorder; autistic Children; Autistic Disorder; Autoantibodies; B-Lymphocytes; Back; base; Behavior; Blood Cells; Brain; calcium indicator; Calcium Signaling; Cell Culture Techniques; Cell physiology; Cell Proliferation; Cell surface; Cells; Child; Color; Complex; Cultured Cells; cytokine; Data; Defect; Development; developmental disease/disorder; Digestion; Disease; Dose; Dyes; early onset; Environmental Health; Etiology; fetal; Flow Cytometry; Flu virus; Frequencies (time pattern); Funding; Gel; General Population; HLA-DR Antigens; Homeostasis; Human; IgE; Immune; immune function; Immune system; Immune System Diseases; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunologics; Label; Laboratories; Lasers; Leptin; Maps; Mercury; Microarray Analysis; Mitogens; Modeling; Mothers; Mus; Nature; neurodevelopment; Neurologic; Oligonucleotides; Pathogenesis; Pathology; Patients; Pattern; Peptides; Peripheral Blood Mononuclear Cell; Phenotype; Plasma; Play; Poly I-C; Population; Population Control; Predisposition; Pregnancy; Principal Investigator; Production; programs; Reagent; research study; response; RNA; Role; Serological; Serum; Source; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Staining method; Stains; System; T-Lymphocyte; Testing; Time; TNFSF5 gene; Tube; Up-Regulation (Physiology); Upper arm; vaccine Antigen; Xenobiotics

STUDY OF HEALTH OUTCOMES IN CHILDREN WITH AUTISM AND THEIR FAMILIES

Abstract Text:
This contract modification is to extend and supplement Contract HHSN271201000033C, consistent with the scope of work of “Study of Health Outcomes in Children with autism and Their Families¿ in order to access the currently validated database developed under the contract to provide for further analysis . Autism Spectrum Disorder (ASD) is a significant public health concern, with an estimated prevalence of 1 in 88 children in the United States. Much of the research to date has focused on the core social and communication deficits of ASD, but there are anecdotes and some survey data suggesting that the rate of comorbid health conditions may also be elevated in this population. Furthermore, despite several large-scale epidemiological studies that have assessed but not found any potential association between ASD and vaccinations, public concerns persist about such a causal link. At least partly as a consequence, health officials in the United States have reported an increased rate of vaccine refusal in the general population. The Study of Health Outcomes in Children with autism and their Families was begun two years ago. Under this contract, the Contractor analyzed a large dataset of retrospective commercial health plan claims of 46,236 children with ASD, their parents and siblings, and a comparison cohort of children and family members. They successfully completed the analyses requested in the original statement of work, which included a study of the validity of ASD diagnoses in the claims data, and descriptions of health outcomes and health care utilization of the ASD cohort, their family members, and the comparison cohorts.

NIH Spending Category:
autism; Brain Disorders; Immunization; Intellectual and Developmental Disabilities (IDD); Mental Health; Pediatric; Prevention; vaccine Related

Project Terms:
Anecdotes; autism spectrum disorder; Autistic Disorder; Child; cohort; Contractor; Contracts; Data; Data Set; Databases; Diagnosis; Epidemiologic Studies; Family; Family member; General Population; Health; health care service utilization; Health Planning; Link; Modification; Outcome; Parents; Population; Prevalence; public health medicine (field); Recording of previous events; Reporting; Research; Siblings; social communication; Surveys; United States; Vaccination; Vaccines; Work

CORE D: MOLECULAR GENOMICS CORE

Core 4 is the Molecular Core. It serves as the central resource for the projects that isolate and process RNA on Affymetrix microarrays, and for performing RT-PCR confirmation of the microarray data for those projects. The UCD Affymetrix Core Facility is run by Dr. Jeffrey Gregg and is equipped with fluidics stations, hybridization ovens, and the new scanner required to scan the human Affymetrix U133 2.0PLUS arrays. Preliminary data from the previous CHARGE study has shown that there are changes in gene expression in the blood of children with autism compared to control children in the general population (GP) and to control children with mental retardation and developmental delay (MR/DD). The blood genomic profile in children with autism without regression (A) was different from controls, autism spectrum disorder (ASD) and different from children with autism with regression (A-R). In addition, there is a group of regulated genes in most children with A, A-R and with ASD that are expressed by natural killer (NK) cells in peripheral blood, suggesting an abnormality in this cell type that is common to all types of autism. These NK-cell related genes are expressed by all of the autism phenotypes including A, A-R and ASD, and hence may point to common pathways that underlie the common language and behavioral abnormalities in all three disorders. This core will be utilized by the projects as follows. Project #1: Aim #1: Perform genomic (RNA expression on microarrays) studies on blood from children with autism in the 4-9 year old range, and compare to the blood genomic profiles we have obtained in children with autism in the 2-5 year old age range. Aim #2. Compare gene expression as a function of blood metal levels in both age groups in A, A-R, ASD, MR/DD and GP groups. Aim #3. Examine genomic profiles in pregnant mothers who have previously given birth to an autistic child to determine if there is a specific genomic profile that correlates with whether the mother’s fetus is destined to develop autism. Project #2. Aim #1. Describe the gene expression profiles in the blood using specific white blood cell subsets including NK cells for children with autism without regression, autism with regression, and ASD children compared to GP and delayed children. Aim #2. Examine gene expression following stimulation or activation of specific white blood cell subsets of A, A-R, ASD, MR/DD and GP children with: low level mercury; immune cell stimulation/activation with vaccine antigens and cell-specific mitogens; and xenobiotics. Project #3. Compare gene expression profiles in the blood of children with autism to the blood of experimental animals exposed to toxicants including organic mercury, PCB 95, and PBDE 47 (Project #3).

NIH Spending Category:
autism; Biotechnology; Brain Disorders; Genetics; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Pediatric

Project Terms:
5 year old; 9 year old; Accounting; Age; age group; Animals; autism spectrum disorder; autistic Children; Autistic Disorder; Autoantibodies; base; Behavioral; Birth; Blood; Blood specimen; cell type; Cells; chemokine; Child; Core Facility; cytokine; Data; Developmental Delay Disorders; Disease; Environmental Health; Fetus; Gene Expression; General Population; Genes; Genetic; Genetic Transcription; Genome; Genomics; Human; Immune; immune function; Inherited; Language; Leukocytes; Mental Retardation; Mentally Disabled Persons; Mercury; Metals; Mitogens; Molecular; Molecular Profiling; Mothers; Natural Killer Cells; Pathway interactions; Patients; pentabromodiphenyl ether; peripheral blood; Phenotype; Polychlorinated Biphenyls; Population Group; pregnant; Principal Investigator; Process; programs; Resources; Reverse Transcriptase Polymerase Chain Reaction; RNA Processing; Running; Scanning; Subgroup; Surveys; Toxic Environmental Substances; toxicant; vaccine Antigen; Xenobiotics

THE CHARGE STUDY: CHILDHOOD AUTISM RISKS FROM GENETICS AND THE ENVIRONMENT

Abstract Text:
DESCRIPTION (provided by applicant): Few rigorous epidemiologic studies have addressed the environmental causes and biologic underpinnings of autism spectrum disorder (ASD). The CHARGE (Childhood autism Risks from Genetics and Environment) Study is a large, population-based case-control investigation of environmental risk factors, broadly defined, in relation to ASD and developmental delay without ASD symptoms, with referents from the general population. Fieldwork began in 2003, and by now CHARGE has published widely on exposures such as air pollution, mercury, flame retardants, maternal nutritional status in the peri-conception, untreated fever during pregnancy, mitochondrial dysfunction, candidate genes, a wide array of functional immune markers in both the child and the mother, and maternal metabolic conditions including obesity and diabetes. This last finding is notable, given the epidemic of obesity and type 2 diabetes that has occurred in parallel with the steady rise in ASD over the last few decades. Moreover, an emerging literature implicates several endocrine disrupting chemicals as contributing to obesity and metabolic dysregulation, including hyperinsulinemia, and to neurodevelopmental disorders as well. This project therefore builds upon these observations in several ways. First, obesity and type 2 or gestational diabetes will be examined in a larger sample, and glucose challenge test (GCT) results for the first time, to determine associations not only with development of ASD and intellectual impairment in the children, but also with specific speech and language delays, behavioral phenotypes such as attention deficits or hyperactivity, and gene expression. Second, these maternal metabolic conditions will be evaluated for associations with markers of both metabolic and immune dysregulation to be measured in neonatal bloodspots. Third, the predictive value of neonatal bloodspot markers for a later diagnosis of ASD or other child developmental and behavioral outcomes will be assessed. Fourth, the maternal metabolic conditions will be analyzed for potential links with upstream exposures to phthalates and anti- bacterial compounds, ubiquitous chemicals in common household products. Finally, this project will examine how gene variants that play a role in biochemical pathways relevant to the processes under study may influence susceptibility of the mother, the neonate or the child. To ensure adequate power for this analysis of gene-environment interaction, the sample size will be increased to 2400 children. This project addresses several goals set by the NIH Interagency autism Coordinating Committee: 1) to discover environmental factors contributing to ASD, particularly in the prenatal period, 2) to understand biological mechanisms for ASD risk, including gene-by-environment interactions, and 3) to identify children at risk for ASD at earlier time points. Results of this detailed inquir into early exposures, maternal pathophysiology and prognostic markers in the newborn will set the stage for developing prevention strategies.

Public Health Relevance Statement:
PUBLIC HEALTH RELEVANCE: This project addresses several issues of direct public health relevance, and the science to be produced will lead to benefits in a wide cross-section of the U.S. population. Because obesity is reaching epidemic proportions and other metabolic conditions such as Type 2 diabetes, gestational diabetes, and dyslipidemia are rising steeply, understanding environmental causes has tremendous public health potential for moving us closer to effective prevention strategies. If environmental chemicals used in common household products do prove to adversely affect body weight, measures can be taken to either reformulate those products, removing them from the market, or to educate consumers on how to avoid them. Similarly, steady increases in ASD might be curbed if the postulated causal pathway is supported by the evidence.

NIH Spending Category:
autism; Behavioral and Social Science; Brain Disorders; Clinical Research; Diabetes; Genetic Testing; Genetics; Intellectual and Developmental Disabilities (IDD); Mental Health; Neurosciences; Nutrition; Obesity; Pediatric; Perinatal Period – Conditions Originating in Perinatal Period; Prevention

Project Terms:
Address; Affect; Age; aged; Air Pollution; Anti-Bacterial Agents; Attention; autism spectrum disorder; Autistic Disorder; Behavior; Behavioral; Biochemical Pathway; Biological; Biological Markers; blood glucose regulation; Body Weights and Measures; C-Peptide; Candidate Disease Gene; case control; CCL2 gene; chemical association; Chemicals; Child; Childhood; Conceptions; cytokine; Data; Development; Developmental Delay Disorders; Diabetes Mellitus; Diagnosis; disorder risk; Dyslipidemias; Endocrine Disruptors; Ensure; Environment; environmental chemical; Environmental Risk Factor; Epidemic; Epidemiologic Studies; ESR1 gene; Exposure to; Fever; Flame Retardants; Functional disorder; gene environment interaction; Gene Expression; General Population; Genes; Genetic Risk; Gestational Diabetes; Glucose; glucose metabolism; Goals; high risk; Household; Household Products; human TNF protein; Hyperactive behavior; Hyperinsulinism; Hypertension induced by pregnancy; Immune; immune function; Immunologic Markers; Impairment; inattention; Inflammation; Inflammatory; Insulin Resistance; insulin sensitivity; interest; Interleukin-6; Investigation; Language Delays; Lead; Leptin; Link; Literature; Marketing; Maternal Exposure; Measures; mercury; Metabolic; Metabolic Marker; Metabolism; mitochondrial dysfunction; Mothers; Neonatal; neonate; neurodevelopment; Neurodevelopmental Disorder; Newborn Infant; Non-Insulin-Dependent Diabetes Mellitus; Nutritional status; Obesity; Outcome; Pathway interactions; Phenotype; phthalates; Play; Population; population based; PPARG gene; Predictive Value; Predisposition; Pregnancy; prenatal; Prevention strategy; Process; prognostic; Prognostic Marker; public health medicine (field); public health relevance; Publishing; Regulation; Risk; Role; RORA gene; RPL10 gene; Sample Size; Sampling; Science; Self Care; Speech Delay; Staging; Symptoms; Test Result; Time; Triclosan; Tumor Necrosis Factor-alpha; United States National Institutes of Health; Variant; Variation (Genetics)

PRENATAL TIMING OF HEAVY METAL EXPOSURES FROM AUTISTIC AND NON-AUTISTIC CHILDREN

DESCRIPTION (provided by applicant): Little is known about the etiology or risk factors for autism, a disease affecting 1 in 50 children in the U.S. While genetic and environmental factors are thought to act together, the specific mechanisms are not known and the measurement of environmental risk factors during critical periods of neurodevelopment has been lacking. This case-control study seeks to apply a novel dental biomarker of early life metal exposure, including in utero, to identify risk factors for ASD. Beyond looking at exposure intensity, we will be able to identify differences in exposure timing between cases and controls. This will allow us to identify critical windows when exposure, even at low levels, increases the risk of ASD. Using the proposed biomarker, we will directly assess fetal exposure, and will not rely on maternal biomarkers which may only provide an indirect measure of fetal exposure to metals. This work will have substantial impact on epidemiologic investigations of the relation of early life chemical exposures to ASD and other neurodevelopmental disorders as it can be used to objectively reconstruct both exposure intensity and timing.

Public Health Relevance Statement:
PUBLIC HEALTH RELEVANCE: Little is known about the causes of autism. This proposal seeks to apply a novel dental biomarker of early life metal exposure, including in utero, to identify risk factors for ASD. Beyond looking at exposure intensity, our application is novel in that we will be able to identify differences in exposure timing between cases and controls. This will allow us to identify critical windows when exposure, even at low levels, increases the risk of ASD.

Project Terms:
Accounting; Address; Affect; Aluminum; analytical method; Animals; Apatites; Arsenic; autism spectrum disorder; autistic Children; Autistic Disorder; Binding (Molecular Function); Biological; Biological Markers; bone; Cadmium; Calcified; Calcium; case control; Case-Control Studies; Chemical Exposure; Chemicals; Child; Childhood; Chromium; critical period; Data; deciduous tooth; Dental; Dentin; Development; Disease; early life exposure; Elements; Environment; Environmental Exposure; Environmental Risk Factor; Epidemic; Epidemiologic Studies; Etiology; Exposure to; fetal; Fetus; Genes; Genetic; Health; Heavy Metals; Human; Immune system; in utero; Investigation; Lead; Life; Literature; longitudinal design; Manganese; Measurement; Measures; mercury; Metal exposure; Metals; Methodology; Methods; mineralization; Mothers; neurodevelopment; Neurodevelopmental Disorder; Nickel; novel; Perinatal; Perinatal Exposure; Play; postnatal; Predisposition; Pregnancy; prenatal; Property; prospective; public health relevance; Recording of previous events; repository; Risk; Risk Factors; Role; Sampling; skeletal; Staging; Time; Tissues; Tooth structure; Toxic Environmental Substances; toxicant; Toxicant exposure; Work

A study comparing vaccinated and unvaccinated kids is coming…and SafeMinds is concerned

10 Jul

If a discussion of autism goes on long enough in the online parent community, the question of vaccines will almost certainly come up. (I’ll note that in real life it rarely, almost never, comes up). If the vaccine topic takes over the discussion, one is very likely to hear the call for a “vaxed/unvaxed” study: a comparison of health outcomes for kids who were vaccinated compared to kids who were not vaccinated.

There are at least three such studies in the works. Two are being funded by groups antagonistic to vaccines. The self-named “National Vaccine Information Center” is funding a project at George Mason University. Said study is, I believe, run by someone from NVIC. Generation Rescue is funding a project at Jackson State University, “Researching into the causes of autism”. In previous years, Generation Rescue was funding Jackson State for a project “vaccination status and health outcomes among homeschool children in the United States”, which is likely the same project just with a different name. Perhaps that’s the same study that the founder of “Focus Autism” is complaining about here. Either way, there are two, maybe more, vaccinated/unvaccinated studies that have been underway for a few years, funded by groups generally antagonistic towards vaccines.

As an aside–in online discussions, the people calling for a vaxed/unvaxed study are connected to Generation Rescue and NVIC. And yet they act like no one is doing such a study.

Back to the topic at hand: there is another vaccinated/unvaccinated study in the works. A large study. In discussions at an IACC meeting this year, Tom Insel responded to a statement about a vaccinated vs. unvaccinated study:

Dr. Insel: So I might add, we have just done that study looking at, in this case, tens of thousands of children in a large health care system — younger siblings, many of whom did not vaccinated. So we could, whether you like it or not, compare what the risks are, both the risk for autism and the risks for medical consequences for not being vaccinated versus being vaccinated in children who have presumably some genetic risk because they’re young sibs.

And those data are submitted for peer review. We should — maybe by July we’d be able to have that presented here. So I’ll be happy to, since we’ve funded that through, be happy to ask the authors to come and talk to us about the results.

That statement was in April. We just had the July IACC meeting but the results were not presented. The study is in the works, though. At the time Dr. Insel made that statement it struck me that this study was likely a part of a project by the Lewin Group. The Lewin Group presented at the IACC in early 2013. That project has not yet been published, but the results presented last year were very interesting, so I’ll take some time to go through those results here. Keep in mind that it’s possible the upcoming vaccinated/unvaccinated study is not by the Lewin Group.

The Lewin Group study population was large and included a large cohort of siblings of ASD kids:

lewin1

When I read or hear “comorbid conditions” discussed by advocacy groups or parents, they are almost always those conditions which those groups feel are part of their “vaccines cause autism” picture. Gastrointestinal complaints–falsely linked by Andrew Wakefield to the MMR vaccine and autism. Mitochondrial/metabolic disorders, brought to prominence by a famous vaccine court case.

Yes, in this study metabolic dysfunction and gastronintestinal/nutritional conditions are about 4.5 times more common in ASD kids. About 20% of kids are in the gastronintestinal/nutritional conditions group (I wonder how that breaks down into GI and nutritional as separate groups). About 5% have metabolic conditions.

But what if I were to tell you that these are not the most common comorbid conditions in ASD children (and ASD adults are yet another story)? Not by a long shot.

lewin2

About 70% of ASD kids have neurological disorders. About 70% have mental health conditions.

70%. 24 times higher than the general population for each condition.

You just don’t hear that from groups promoting vaccine causation. Groups like SafeMinds. Which brings us back to the vaccinated/unvaccinated study SafeMinds is concerned about. SafeMinds is preparing its readers for the vaccinated/unvaccinated study. Although they’ve been calling for this study for a long time, a fact they remind us of this fact in their article: The NIH is slated to release the results of a study on autism in vaccinated, partially vaccinated, and non-vaccinated children. Here’s what you need to know BEFORE it comes out.

SafeMinds begins their article comes with what I consider a rather ironic graphic:

SafeMindsBlowsAnIronyMeter

Why is this ironic? SafeMinds relies upon poorly done research to support their arguments about vaccines, mercury and autism. For example, their non-peer reviewed Autism: A Novel Form of Mercury Poisoning is one of the papers that first made me question the purported vaccine/autism link. It was never very good and really should be discarded. As another example, if you go the SafeMinds web page
Correlation Between Increases in Autism Prevalence and Introduction of New Vaccines you will find this graph:

california-autism-prevalence

If you think that graph looks old, you’d be correct. It’s at least 10, if not 15 years old. It takes California Department of Developmental Services (CDDS) administrative data, pretends it’s actually autism prevalence, and graphs it against the mercury exposure from infant vaccines during the 1990’s and leads the reader to the idea that mercury exposure and autism are correlated and also related. But they aren’t correlated. That’s what happens when you use a 15 year old graph. California removed thimerosal from infant vaccines, even the flu shots, and also for vaccines for pregnant women. And what happened to the autism rate? It kept going up. Schechter and Grether published this in 2008 in Continuing increases in autism reported to California’s developmental services system: mercury in retrograde. In 2013, I showed that the increase was still going on. But SafeMinds is acting like the last decade didn’t happen. They tell us:

Autism prevalence increased rapidly in the late 1980s. The epidemic increased simultaneously in states across the United States, indicating that U.S. children were exposed to toxins in a consistent manner across the entire country. Due to the high adherence amongst the states to the CDC-recommended vaccination schedule, vaccines typically introduce a new exposure to children simultaneously throughout the country.

For people who actually looked at the CDDS data, we know the idea that autism was rising in the same way in various locations wasn’t true. The whole basis for a universal exposure causing the rise in identified autism was false. It’s one of those facts that made me question the vaccine hypothesis long ago. CDDS data even in 2000 showed autism rates varied wildly across the state of California and the increase was not the same from region to region within the state. Special Ed data (which has major limitations but is likely the data SafeMinds was using to make the above statement) showed large variation from state to state in the number of people getting services under the autism label. There is not and never was data to support the assertion SafeMinds makes above that the rates of autism increased simultaneously across the US.

All this is my long-winded way of saying, I find it more than ironic that SafeMinds wants to warn me about flawed research leading to bad conclusions.

So, let’s ask ourselves: why would SafeMinds be concerned enough about this new vaccinated/unvaccinated study? Well, siblings of autistic kids are (a) more likely to be unvaccinated and (b) more likely to be autistic, like 20 times more likely to be autistic (here and here)

The Lewin group reported that younger siblings were less likely to be vaccinated:

lewin3

In addtion, an unpublished study from 2011 compared vaccination status among ASD kids, their siblings and non-relatives. The authors found:

Instead, because siblings of children with autism were less likely to be vaccinated according to the recommended schedule, both correlations and multiple regressions revealed a significant relationship between higher rates of vaccination and non-ASD behavioral outcomes.

Or, to put it simply, if you look at younger siblings, they get fewer vaccines than the general public and have a higher rate of autism. If correlation is causation, this would mean that vaccines prevent autism. Which, in at least one case, is true. Correlation is not causation, though. The new study will likely find that delaying or forgoing vaccines does not reduce autism risk. And that, in my view, would concern SafeMinds. Enough that they want people prepared in advance for what to them will be “bad” news.


By Matt Carey