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Urinary opioid peptides and genes

19 Mar

Two new interesting pieces of science out this week.

Firstly was the latest piece of MMR hypothesis destroying science called ‘Absence of urinary opioid peptides in children with autism’.

MMR believers say that part of the hypothetical damage the MMR does to the gut of autistic kids is cause so-called ‘leaky gut’ syndrome, an alternative medicine hypothesis roughly suspected to be on a par with homeopathy and massaging aura’s in terms of scientific credibility.

Proponents of the autism branch of this hypothesis say that the MMR causes leaky gut and that the ‘leak’ fails to parse these urinary opioid peptides which in turn would (in effect) get the patient stoned. or to put it another way:

….these peptides result in effects which are basically opioid in nature (akin to drugs such as morphine) and that they may either, themselves, have direct opioid activity or that they may form ligands for the enzymes which would normally break down such opioid peptides that occur naturally within the Central Nervous System (CNS). In either case, the consequence would be the same. The CNS neuroregulatory role, which is normally performed by the natural opioid peptides such as the enkephalins and endorphins, would be intensified to such an extent that normal processes within the CNS would be severely disrupted…

Yeah, right.

So now some actual science (as oppose to blueskying) has looked at this. And what do they conclude:

It has been claimed for a number of years that the urine of children with autism contains exogenously derived opioid peptides. This finding is said to reflect a disturbance in the integrity of the gut epithelium, act as a diagnostic marker for autism and predict treatment response to a diet excluding gluten and casein. The aim of the present study was to determine whether exogenous or endogenous peptides were present either in the urine of children with autism, or control children.

…..

There were no significant differences between the HPLC urinary profiles of the children affected by autism and the typically developing controls. In those cases where HPLC showed peaks in the locations at which opioid peptides might be expected to be found., MALDI-TOF established that these peaks did not, in fact, represent opioid peptides at all.

……

Given the lack of evidence for any opioid peptiduria in children with autism it can neither serve as a biomedical marker for autism, nor be employed to predict or monitor response to a casein and gluten exclusion diet.

So that’s yet another nail in the undead vampire of the MMR hypothesis (in fact, is there a proper word for something which is less than a hypothesis? Even using the word ‘hypothesis’ now seems aggrandising this silliness)

On the other side of research, where actual progress is being made, an as yet unpublished study (or published but the journal issue hasn’t been released or it has and I can’t find it) has found genetic connections which they think can count towards up to 2.5% of autism:

Disruptions in the gene, called contactin 4, stop the gene from working properly and appear to stop the brain from making proper networks, the researchers reported in the Journal of Medical Genetics.

These disruptions, in which the child has either three copies of the gene or just one copy when two copies is normal, could account for up to 2.5 percent of autism cases, said Dr. Eli Hatchwell of Stony Brook University Medical Center in New York, who led the study.

Now, when we put this together with Rett, Fragile-X, Tuberous Sclerosis, de-novo mutations and a few others I can’t recall I think we’re approaching between 10 – 16% of an established genetic cause for autism(s). Slightly better than the 0% that the vaccine hypotheses are running at.

Autism vs features of autism

14 Mar

In sum, DVIC has concluded that the facts of this case meet the statutory criteria for demonstrating that the vaccinations CHILD received on July 19, 2000, significantly aggravated an underlying mitochondrial disorder, which predisposed her to deficits in cellular energy metabolism, and manifested as a regressive encephalopathy with features of autism spectrum disorder.

– HHS

If one has the right set of “features” of autism, one has autism……Hannah Poling has autism — as defined in every book, in every library, in every university in the world. Dr. Parikh’s insistence otherwise is perplexing.

– David Kirby, to EoH group in response to Dr. Parikh’s article in Salon.

Its a massively ambiguous point. Do ‘features of autism’ equate to a _diagnosis_ of autism? David Kirby and some commenter’s to this site say ‘yes’. I personally think ‘no’.

But I think we need to be clear here. In this particular case, Hannah Poling can still be autistic but the HHS are arguing (in my opinion) that the features listed as those being aggravated/caused by vaccines do not add up to enough by themselves to give a diagnosis of autism.

To illustrate this idea, I went through the symptoms given by Dr Zimmerman that he put forward as being vaccine aggravated in a previous post (green = hit with DSM (IV), red = miss):

1) Loss of previously acquired language
2) Eye Contact
3) Relatedness
4) disruption in CHILD’s sleep patterns,
5) Persistent screaming
6) Arching
7) the development of pica to foreign objects,
8) loose stools
9) CHILD watched the fluorescent lights repeatedly during the examination

So, three of the symptoms given by Dr Zimmerman as being vaccine aggravated can be matched with the DSM (IV). This is way below what is needed for a diagnosis of autism.

But, we cannot discount the idea that she _could be_ autistic. To me, it seems likely that here is an autistic child who has her vaccines and who presents with nine symptoms following those vaccines, three of which tally with DSM (IV) criteria.

This presents two questions. First, is there a difference made by autism diagnosticians about autistic features vs a diagnosis of autism?

The best way to answer this is to ask autism diagnosticians. I wrote to some autism diagnosticians. They asked to remain anonymous, which I have to respect. The email I sent in essence asked them if they thought that:

a) ‘with features of autism spectrum disorder’ is directly equivalent to a diagnosis of autism?
b) ‘with features of autism spectrum disorder’ means that some elements of the DSM (IV) are present but not enough to diagnose autism?
c) ‘with features of autism spectrum disorder’ means that some elements of the DSM (IV) are present but not enough to diagnose ASD?
d) ‘with features of autism spectrum disorder’ means something else entirely?

The responses I got back stated that b) was most likely, maybe c) .

So according to these autism diagnosticians, some elements of the DSM (IV) are present but not enough to diagnose autism, or possibly ASD. This tallies with my own personal opinion.

The second question is; did Hannah Poling present with any diagnosable symptoms of autism _before_ her vaccines? Sadly, it seems we will never accurately know the answer to this question. The Poling’s will say no of course. David Kirby et al will say no of course.

I will remember the Cedillo’s however, who testified that their daughter (who they claimed was made autistic by vaccines) showed no symptoms of autism before her vaccines were administered. However, when home movies of their daughter taken before her vaccines were shown to several diagnosticians, they testified that she was indeed exhibiting symptoms of autism prior to vaccine administration. The Cedillo’s didn’t lie. Its simply not possible to remain clinically objective about one’s own child. Even for an employee of Johns Hopkins, it is not possible to remain objective about one’s own child.

That doesn’t mean Hannah Poling _did_ exhibit symptoms of autism prior to vaccines of course. It simply means that we need to be skeptical of the claim that she didn’t.

Is Hannah Poling autistic? Could be. Seems likely.

Did the vaccines cause the nine symptoms Dr Zimmerman found? HHS ‘concede’ they did.

Do the fact that three of those nine symptoms tally with the DSM (IV) mean that the vaccines are the cause of her autism? No, thats not logical.

Vaccines, Autism and the Concession

1 Mar

1) Concession Report (This document has been removed due to the possibility of it being illegally obtained). If people really wish to read the document for themselves it can be founf here, at the Huffington post
2) Zimmerman Case Study

When David Kirby wrote his piece in the Huffington Post, I’ll admit I read it with my jaw on my chest. Here was evidence I was wrong. I emailed David Kirby to get the whole report from him and he was kind enough to provide not only a PDF version but a plain text version as well.

This enabled me to contact a few people that I know are medical people and/or scientists and/or closely connected to this case. For example I contacted Dr Zimmerman and learned that it was not possible for him to offer any sort of opinion on this case due to the fact that his patients parents had not allowed him to discuss his thoughts and opinions with anyone except the court. I was told however that ‘the comments on your site with questions raised and loopholes pointed out about the way others are interpreting the facts of the situation, are right on track.’

It is clear to me then that there is some wordsmithing going on – either deliberately or unintentionally. What we need to do is look closely at the wording of two documents. The concession report and the case study performed by Dr Zimmerman.

The claim by David Kirby et al is, in essence, that the US Government have conceded that vaccines cause autism in this one case. Lets look at the so-called concession report in relation to what it says about autism.

Dr. Andrew Zimmerman, a pediatric neurologist, evaluated CHILD……on February 8, 2001. Dr. Zimmerman reported that after CHILD’s immunizations of July 19, 2000, an “encephalopathy progressed to persistent loss of previously acquired language, eye contact, and relatedness.” He noted a disruption in CHILD’s sleep patterns, persistent screaming and arching, the development of pica to foreign objects, and loose stools. Id. Dr. Zimmerman observed that CHILD watched the fluorescent lights repeatedly during the examination and would not make eye contact. He diagnosed CHILD with “regressive encephalopathy with features consistent with an autistic spectrum disorder, following normal development.”

Features consistent with. He did not diagnose her with autism. What were these features?

1) encephalopathy progressed to persistent loss of previously acquired language,
2) eye contact,
3) relatedness
4) disruption in CHILD’s sleep patterns,
5) persistent screaming
6) arching,
7) the development of pica to foreign objects,
8) loose stools
9) CHILD watched the fluorescent lights repeatedly during the examination
10) would not make eye contact

Of these ten, one is repeated (eye contact issues) so I make nine clear separate symptoms there. Which of these appear in the DSM (IV)? Green equal matches, red equal misses.

1) Loss of previously acquired language
2) Eye Contact
3) Relatedness
4) disruption in CHILD’s sleep patterns,
5) Persistent screaming
6) Arching
7) the development of pica to foreign objects,
8) loose stools
9) CHILD watched the fluorescent lights repeatedly during the examination

To meet the DSM(IV) criteria a person must meet no less than 6 of the criteria. So, as described perfectly exactly by the Dr Zimmerman in the concession report, this child has features consistent with an ASD. But its clear she does not meet the criteria for autism.

Later on,

CHILD was evaluated by Alice Kau and Kelley Duff, on May 16, 2001, at CARDS. The clinicians concluded that CHILD was developmentally delayed and demonstrated features of autistic disorder.

Almost the exact same phrasing. Consistent with. But no one has said thus far that the child has been diagnosed with an ASD.

The concession report concludes with:

the vaccinations CHILD received on July 19, 2000, significantly aggravated an underlying mitochondrial disorder, which predisposed her to deficits in cellular energy metabolism, and manifested as a regressive encephalopathy with features of autism spectrum disorder….

This is the phrasing that caused the uproar. But when looked at in light of the previous, it is clear that far from suggesting that vaccines cause autism via a mitochondrial disorder, the vaccines worsened an occluded or underlying mitochondrial disorder which took on a few of the symptoms of autism _but was never actually diagnosed as autism at all_ . Because it wasn’t autism.

Before we switch to Dr Zimmerman’s Case Study, lets clear up a few things.

No one, I repeat, no one is saying this child wasn’t autistic. She may well have been. What we are doing is looking at the science reported in the concession report and Zimmerman’s paper and seeing if what the _science_ says in these two papers means that it was the vaccines that caused any autism. The concession report clearly says that no it wasn’t. Thats why this case was uncontested. She was affected by her vaccines but autism was not the result.

Zimmerman’s case study is entitled ‘Developmental Regression and Mitochondrial Dysfunction in a Child With Autism’ – this is further evidence against the case presented that it was the vaccines that caused the autism. This child is reported as being one with autism. Not one who develops autism as a result of vaccines.

However, it is clear that this child _does_ develop autism:

We describe a female patient in whom developmental regression and autism followed normal development…..Evaluation at 23 months showed …..[t]he Childhood Autism Rating Scale (CARS) score was 33 (mild autism range), and she also met Diagnostic and Statistical Manual for
Mental Disorders-IV criteria for autism

and yet this autism was so mild that at that exact same period (23 months):

the patient began speaking again at 23 months old

which means that expressive language was lost for a sum total of one month (it is reported being lost at 22 months). It should also be noted that CARS is _not_ designed for diagnosis but is an indicator only. Overall, we get a picture of a child who had an underlying mitochondrial dysfunction exposed by the illnesses following her vaccinations which caused developmental regression. This developmental regression presented with some features of autism.

Did the vaccinations cause her developmental regression? Seems likely. It is an undisputed fact that vaccines do cause injury, that is why after all there is a compensation program to claim from in the US and the UK.

Was her developmental regression autism? No. At no point in either the concession report is it claimed that the developmental regression the child went through _was_ autism. However, in the same way that Leukemia (weakness, paleness; fever and flu-like symptoms) can have the same symptoms as flu (weakness, paleness; fever and flu-like symptoms) but be totally different, this child’s developmental regression shared certain features of autism.

So was this child autistic. She might well have been. However, her autism was not caused by a vaccine.

Update

This column was forwarded to me by a friend. Thanks to him.

The practice of calling certain things near-autism, or even autism itself is not new. Here’s a quote from a Science article regarding HIV in 1989:

The signs of AIDS dementia in children are clear and, Pizzo says, “very painful to watch. Very young children lose words.” Words like “mommy” and “daddy” and “bear” are too hard to remember as the AIDS virus multiplies in the young child’s body and penetrates the central nervous
system.

An 8-year-old boy, once normal, was rendered practically autistic by HIV, Pizzo said. He stopped speaking. Asked to trace a simple
outline of an elephant, the boy could not. Painfully, he knew what a simple task it was, and he knew he was failing it. But he could not cry even though his doctors could see tears welling up in his eyes.

Pizzo has seen children lose IQ points one boy lost as many as 28-as AIDS ravages their brains. “Kids who used to do well in school really deteriorate,” says Pizzo who has “before and after” IQ data from school-age children.

But in a series of remarkable studies, Pizzo has seen AZT (azidothymidine) reverse these symptoms. The child who lost words like “mommy” and “daddy” “got them back,” Pizzo says. The boy who lost IQ points is restored to his former capacity.

The 8 year old cries. After just a couple of weeks of continuous AZT therapy, the boy who could not trace an elephant is successful at tracing a horse.

Now, we all know that ‘tracing an elephant’ and losing IQ points are not symptoms of autism but it is intriguing to see a doctor describe a regression as ‘practically autistic’. Note also, just like in this case, in Zimmermans case study, the child quickly loses, then very quickly regains aspects of their former regression. But HIV didn’t cause autism any more than vaccines did.

US government concededs vaccine/autism case

26 Feb

As per this story from David Kirby in the HuffPo.

I have some doubts about it but lets see. I’ve emailed David Kirby to ask him to provide me with a full copy of the concession. His willingness to provide this information as well as the information itself should tell us more about what this concession report contains.

Ya ken that hidden horde, aye?

24 Feb

So – the ‘Hidden Horde’ – the term that anti-vaccinationists like to smirk about as evidence of an autism epidemic. The logic goes like this: if there’s no autism epidemic then where are all the [insert age here] year old autistic adults? I’ve heard people asking for evidence of 75 year old autistics (conveniently forgetting that the average mortality age in the US and UK is around 70), 50 year olds – even 30 year olds.

Never mind that there’s been plenty of evidence for adult autistics. Thats not convenient for the anti-vaccinationist agenda so it gets ignored.

Anyway, todays Sunday Herald carries another story about adult autistics in Scotland called ‘Revealed: ‘invisible’ adults living with autism’.

According to the National Autistic Society (NAS) Scotland report, due to be launched this week, 52% of adults have not had an assessment of their needs since the age of 18…..It is estimated that more than 35,000 adults in Scotland have the condition, but campaigners said they were “invisible” to local authorities, who are failing to record the number of people with autism in their area.

The population of Scotland is 5,062,011. The latest prevalence estimates for the UK are 1 in 100. This means that 50,620 people are autistic. If 35,000 adults in Scotland are autistic then 69% of autistic people in Scotland are adults.

Hidden horde aye?

New mercury/autism paper to misrepresent

22 Feb

A new study on autism and mercury has been published:

Autism is a highly heritable disorder, however, there is mounting evidence to suggest that toxicant-induced oxidative stress may play a role. The focus of this article will be to review our animal model of autism and discuss our evidence that oxidative stress may be a common underlying mechanism of neurodevelopmental damage. We have shown that mice exposed to either methylmercury (MeHg) or valproic acid (VPA) in early postnatal life display aberrant social, cognitive and motor behavior.

Some people have reported on this study thusly:

New Study Implicates Mercury In The Development Of Autism

Um, right.

These same people, well known for their anti-vaccine beliefs, fail to note anywhere that this study says:

…., it is important to note that autism was not found to be associated with either pre- or neonatal exposure to organic mercury.

One form of organic mercury being, of course, thiomersal.

Might it be very uncharitable of me to suggest that this was a deliberate obfuscation? I guess it might but I still think it was. Especially when this same person says:

….will they all continue to proffer the lie that there is no convincing evidence linking vaccines to autism, while ignoring all the studies that are piling up on the hard drives of parents across the country?

Hmmm, so this study quite categorically states there is no link between organic mercury and autism and yet this person calls others liars? Projection is a terrible thing.

There will be more to say on the quality of this study – especially its references – but I wanted to get this clear as soon as possible.

Wakefield, Baird, Archives

20 Feb

This is a Guest Blogged post, written by an author with a keen interest in Wakefield related issues. My gratitude to Nigel for writing the post which follows.

Wakefield and his colleagues were fast off the mark (http://www.thoughtfulhouse.org/pr/020608.htm) to criticise the study by Baird et al which recently appeared in Archives of Disease in Childhood. This was a well conducted study which failed to detect measles virus (MV) or elevated measles antibodies in the blood of autistic children. There is a general feeling that even if the almighty Jehovah himself, collaborating with the top researchers at the Universities of Oxford, Cambridge, Harvard and Yale, and with an advisory board of all recent Nobel laureates in medicine, produced a negative study on measles virus in autistic children, Wakefield would still find flaws in the work; remarkably rich from the single largest purveyor of junk science in the last 20 years.

As a criticism of the study Wakefield states “It is a major error to have presumed that peripheral blood mononuclear cells are a valid ‘proxy’ for gut mucosal lymphoid tissues when searching for persistent viral genetic material” and later states “ We are increasingly persuaded that measuring things in blood many years down the line tells us very little about the initiating events in what is, in effect, a static (non-progressive) encephalopathy unlike, for example, subacute sclerosing panencephalitis, which is a progressive measles encephalopathy” .

The hypocrisy of this statement is quite breathtaking, but unsurprising from someone whose relationship with scientific honesty and integrity is somewhat elastic. For those who don’t have long memories, the first “alleged “ evidence of MV in autism came from Wakefiled’s collaboration with Kawashima where using standard methodologies which were highly effective at detecting MV laboratory contaminants, Wakefield claimed that blood cells from 3/9 autistic children gave positive results ( Dig Dis Sci 2000 45:723-9). This paper formed a key part of the UK MMR litigation from 2000-2003 driven by Wakefield himself until it was mysteriously dropped from the final claimants witness reports by Wakefield himself. Perhaps the realization that blood is a poor proxy for gut came to him in 2003, or more likely, that he knew the Kawashima data were junk and would not stand up in court.

Even more staggeringly, the vast majority of samples from autistic tested for MV by O’Leary in the Unigenetics lab in Dublin were from blood; including the now infamous blood samples taken from healthy children at Wakefield’s own child’s birthday party. Steve Bustin in his testimony on the US Cedillo case comprehensively shredded all of the work that came out of that lab. All of this data on blood has never appeared in the public domain although the junk science on MV in the gut did appear in the Uhlmann paper, in a low impact factor journal which promptly rolled over and died.

As always however, you cannot believe anything Wakefield says as being scientifically valid. In the blood there are cells which are representative of the gut lymphoid tissue. This is very well established and non-controversial. When T and B cells are activated in the gut associated lymphoid tissue, they acquire the alpha4beta 7 integrin and migrate via the mesenteric lymph nodes, and the thoracic duct into the circulating blood and then home back into the rest of the gut using the mucosal addressin, MAdCAM-1.. This happens in all healthy people constantly and it is possible to identify these gut-homing cells in blood. Since Wakefield claims that MV persists in the allegedly large lymph nodes in the gut wall, cells should be infected with MV at source and carry the virus with them into the blood. So come on Andy, with O’Leary’s supersensitive PCR, you should be able to detect at least some of these cells migrating to the gut via the blood. After all, the PCR is so sensitive it can detect MV in samples of distilled water, now that is really amazing!

I suppose one should always rejoice in the repentance of a sinner, and if Wakefield has now come to the conclusion that blood is not a proxy for gut lymphoid tissue, we should be happy he is now happy to recant on all his previous claims about blood cells being positive for MV in autism. I have a sneaky feeling however that this is just another “wriggle” to keep the show on the road. If one of his acolytes claims to find MV in blood of autistic children, you can bet that blood will once again become a valid proxy for gut lymphoid tissue.

Andrew Wakefield Responds

14 Feb

Andrew Wakefield has responded to the latest MMR Study showing no link between the vaccine and autism.

Just to recap, the latest Baird et al study looked at whether autistic kids and non-autistic controls showed any variance in their measles antibody response. They don’t.

The measles aspect of the MMR vaccine is what Wakefield’s hypothesis relies on. He says because its a live virus its casing gastric issues and then autism in some kids. This study looked to see if there was any evidence of measles-virus in the blood of these kids. There wasn’t. They looked to see if any of the autistic kids had evidence of gastric issues over and above the average. They didn’t.

But Wakers thinks this isn’t good enough.

The study is severely limited by case definition in the context of the crucial ‘possible enterocolitis’ group………….We have over the last 10 years evaluated several thousand children on the autistic spectrum who have significant gastrointestinal symptoms. Upper and lower endoscopy and surgical histology have identified mucosal inflammation in excess of 80% of these children. Almost none of these children with biopsy-proven enterocolitis would fit the criteria set out above………….The requirement for the current presence of these symptoms, for 14 or more days continuously, shows a singular lack of understanding of the episodic, fluctuating, and alternating (e.g. diarrhea/constipation) symptom profile experienced by these children

Wakers thinks that the criteria for defining enterocolitis that Baird et al used was too strict. He says it will occlude the group he’s identified.

He’s probably right. But not in the way he thinks he is. Could it maybe be that _his_ definition of enterocolitis is too slack? His definition includes:

In our experience, ASD children with histologic enterocolitis typically have 1 to 2 unformed stools per day that are very malodorous and usually contain a variety of undigested foodstuffs. This pattern alternates with that of “constipation” in which the unformed stool is passed after many days of no bowel movements at all, and with excessive straining.

With which he claims is ‘identified mucosal inflammation in excess of 80%’ of his kids.

Thing is, a PubMed search for ‘mucosal autism’ returns 20 results. Of which only one support the idea of inflammation – One of Wakers own papers. In fact the only person I could see using the term ‘histologic enterocolitis’ was (you guessed it) AJ Wakefield.

The question immediately occurs: Of the ‘several thousand children on the autistic spectrum who have significant gastrointestinal symptoms’ why hasn’t there been any published, peer-reviewed, replicated, science written up by Wakefield? Why hasn’t anyone else managed to find 80% positive results and published peer reviewed science about their results?

Could it be that its only the team who have screwed up their results that find what they want to find? I think so. Lets quote Stephen Bustin once more.

Now, these are from samples that should have been discarded according to the SOP from Unigenetics because there was no GAPDH present, i.e., the RNA is degraded. If you look at the Cts for the F-gene which they reported as positive you can see they’re the same. Now, if this is degraded RNA yet I’m getting the same Cts for my F-gene target this can’t be RNA because it would have been degraded.

That’s what the GAPDH showed me. Now, if it isn’t RNA it has to be DNA. If it is DNA it can’t be measles virus it has to be a contaminant.

Plain English – Wakefield scoped kids. Sent samples to Unigenetics. They should’ve told Wakers the samples were rubbish. They didn’t. They analysed rubbish samples which were contaminated. What they found wasn’t measles virus.

A frequent complaint from the Wakefield apologists is that by analysing blood samples rather than gut tissue, science teams are not comparing like-for-like. There are a number of reasons why this is questionable.

Firstly, there has to be a _reason_ for scoping children. It is not a straightforward procedure.

Towards the end of last year, an autistic child who was scoped following a recommendation by Simon Murch, a colleague of Andrew Wakefield’s, was awarded £500,000 damages after his bowel was perforated in 12 places.

An autistic boy has won a £500,000 payout after the hospital at the centre of the MMR scandal carried out an operation that was ‘not clinically justified’.

Jack Piper, then five, was left battling for life after the procedure, which his parents claim was carried out to establish links between his condition and bowel problems.

His bowel was perforated in more than 12 places during surgery at the Royal Free Hospital in North London.

…………

The colonoscopy was suggested by Professor Simon Murch. He is being investigated by the General Medical Council over allegations that he carried out invasive tests including colonoscopies on 11 other children contrary to their best clinical interests.

It is an ethical issue – is a scoping procedure ethically justified? The answer is ‘no’ – that hasn’t stopped Wakers doing ‘thousands’ though apparently.

Secondly, is there any reason why looking blood is not good enough? Awhile ago, I asked a Doctor (who wished to remain anonymous) who told me:

measles is a lymphotropic virus, even more so for the vaccine strain which has been selected to exploit the CD46 cellular receptor. If there is a persistent MV infection the most logical place to detect it is in cells that it is most adept at infecting. Lymphocytes [a type of blood cell]

(Insert mine).

So, there’s not really any reason why blood cells wouldn’t be suitable to check for measles virus, despite Wakefield’s opinion.

And in fact, at least one team _wanted_ to use Wakefield’s samples but their request was ignored:

The groups of investigators that either had access to original autism specimens or investigated them later for measles virus detection were invited to take part in the study but failed to respond. Similarly, it was not possible to obtain clinical specimens of autism cases from these investigators for independent investigations.

Now I have to wonder why, if Wakefield et al are claiming that only scoped samples are any good, or that blood is no good they didn’t hand over the samples they had harvested with the gratitude of a team expecting to be replicated.

Maybe they didn’t really want another science team looking at these samples. Maybe they feared what another team would find.

And what about this inflammation Wakefield alleges to have found? Turns out that its possible to screen for inflammation without the need for scoping.

Fecal calprotectin is a marker for a range of gastric issues, notably IBD (irritable bowel disease) and Crohn’s which it has positive results for.

A 2002 study Effect of Pentavac and measles-mumps-rubella (MMR) vaccination on the intestine looked at:

if MMR vaccination is associated with subclinical intestinal inflammation, which is central to the autistic “enterocolitis” theory

To do this, the team:

….studied 109/58 infants, before and two and four weeks after immunisation with Pentavac and MMR vaccines, for the presence of intestinal inflammation (faecal calprotectin).

The results were:

There were no statistically significant differences in faecal calprotectin concentrations at any time points (p>0.25) or when assessed in subjects studied before and after Pentavac (p>0.2) or MMR (p>0.3) vaccination

and

There was no evidence that either Pentavac or MMR vaccination provoked subclinical intestinal inflammation in any of our apparently healthy children during the four week post-vaccination period. This lack of a detectable intestinal inflammatory response suggests that the measles vaccine virus itself is not enterotoxic in healthy infants which argues against the MMR induced autistic “enterocolitis” theory.

And so we come back to the bottom line. What direction does peer reviewed published science take us in? It takes us away from Wakefield.

There are no good reasons to believe that blood samples are not good enough to compare with gut samples and if Wakefield believes otherwise, why didn’t he provide the samples to the Afzal team when asked to?

There is no good reason to justify dangerous, invasive procedures such as the one Wakefield has used on thousands of kids and which left one child fighting for life with a massively perforated bowel. Fecal calprotectin is more than adequate as a marker of intestinal issues and using this method reveals no association between MMR and autism.

MMR Smoke and Mirrors

8 Feb

In the days following the latest in an increasingly long line of studies repudiating the MMR/autism hypothesis, adherents to this belief system have clung wildly to the flotsam and jetsam that is pretty much all that is left to hang on to.

On the ADC Online forum, John Stone encapsulates this position with a letter I’ll go through point by point:

Of the original 1770 Special Educational Needs (SEN)cases in this study 255 were Autistic Spectrum Disorder (ASD). Of the 1770 735 dropped out, then a further 780 were excluded for reasons which are not transparent. 255 were left (a different 255 from before): some ASD, some just SEN but we do not know in what proportion. Then, exactly 100 were excluded because of inadequate blood tests. Of the remainder 101 had ASD (less the 40 per cent of the original 255 autistic cases). None is reported to have bowel disease (the sub-group of Wakefield’s study) or adverse reaction to MMR.

This is numerical hoopla and means nothing. The key to Stone’s frustration is the last sentence of this paragraph and the first one of the next:

It is not clear what the scientific purpose of this study is…….None is reported to have bowel disease (the sub-group of Wakefield’s study) or adverse reaction to MMR. This, of course, makes this a distinct group from the children referred to Andrew Wakefield and his colleagues at the Paediatric Gastroenterology department of the Royal Free Hospital in the 1990s and slighlty beyond.

Stone is arguing that because none of the ASD subjects were found to have bowel issues that disqualifies them as being like Wakefield’s subjects.

Methinks someone has missed the point.

The issue is one of clinical science. Wakefield claims to have found a clinical link between the measles live virus component of the MMR which causes bowel issues with associated autism. However, the Cedillo hearings drove a rather large nail into that particular coffin.

Professor Stephen Bustin is the worlds foremost PCR expert. Bustin uses PCR every day in his work, he has 14 papers in the peer reviewed literature on PCR, over 8 book chapters and is personally the author of the ‘A to Z of Quantitative PCR’ which is considered ‘the bible’ of PCR. One of his papers has been cited over 1,000 times. Another has been cited over 500 times. He both organises and speaks at international PCR conferences. His testimony regarding the Unigentics lab used to find the measles virus in the guts of these autistic kids was invaluable.

Bustin examined the Unigentics lab findings and procedures in great detail (spending over 1,500 hours in the lab itself) and found that the lab (which has now gone bust as a business) made a fairly basic error of science when looking at Wakefield’s samples:

“…Now, these are from samples that should have been discarded according to the SOP from Unigenetics because there was no GAPDH present, i.e., the RNA is degraded. If you look at the Cts for the F-gene which they reported as positive you can see they’re the same. Now, if this is degraded RNA yet I’m getting the same Cts for my F-gene target this can’t be RNA because it would have been degraded.

That’s what the GAPDH showed me. Now, if it isn’t RNA it has to be DNA. If it is DNA it can’t be measles virus it has to be a contaminant.”

In other words, the samples Wakefield provided to Unigentics were useless because Unigenetics own documented lab procedure says they were. But they used them anyway. The results were a bombshell. If the RNA is useless (which the lab process defines it as being) it can’t actually be RNA. If its not RNA then it must be DNA and if its DNA then it can’t be measles virus because measles virus doesn’t exist as DNA.

What the Unigentics lab detected in Wakefield’s samples were contaminants. There’s no way that Unigentics could possibly have been detecting measles virus.

This was backed up by Chadwick who checked Wakefield’s work (at his request). He also did a PCR test.

Q. What results did you receive from the gut biopsy materials for measles RNA?
A. They were all negative.

Q. They were always negative?
A. Yes. There were a few cases of false positive results, which I used a method to see whether they were real positive results or false positive, and in every case they turned out to be false positive results. Essentially all the samples tested were negative.

Q. Did you inform Dr. Wakefield of the negative results?
A. Yes. Yes.

So not only are the samples Wakefield provided useless, the testing he asked Chadwick to perform showed they were useless. And yet he went ahead anyway.

Its also worth noting that every subsequent piece of MMR science (save one unpublished poster presentation) went through Unigenetics lab and went through the same process as Wakefield’s.

So lets be frank – the idea that Wakefield found measles virus in the gut of autistic kids is plain and simply wrong. He screwed up.

The issue then becomes one of probabilities: given that there is no scientific reason to believe MMR causes autism with bowel disorders, it is nonsensical to only look at autistic kids with bowel disorders. And in answer to Stone’s question ‘It is not clear what the scientific purpose of this study is…’ the answer is plain – it has scientifically illustrated that autistic kids had exactly the same measles antibody response as non-autistic kids. No difference. At all.

Stone continues to attempt to muddy the scientific waters:

There is presently not enough consensus about the etiology of ASD to assume there is any single origin, nor anything to rule out ASD subjects having gut symptoms which justify on occasion invasive procedures. The NAS apparently consider that there is a sub-group which is being denied sympathy, investigation or treatment, and this is in itself troubling. It also suggests that this study is not representative since no such cases are included, and it does not address their problems.

This is slipperiness taken to almost artistic levels. Stone is quite right there is no consensus about etiology of autism. That does not mean we cannot say what doesn’t cause it though. And based on the available science, MMR ain’t it.

The paper further does not attempt to claim that autistic kids don’t have gastric issues and Stone’s implication that it does and his attempt to gain the mainstream ground by invoking the name of the NAS is grasping and dishonestly representative of the NAS’s statement. They do _not_ claim, infer or consider that there is any such sub-group. What they suggest is that the MMR debacle has led to some doctors dismissing some parents fears about their kids bowel issues as hysteria. This is, of course, unacceptable but Stone is simply attempting to manipulate the NAS statement for his own ends.

“The NAS warning relates to the GMC hearing involving doctors Wakefield, Walker-Smith and Murch which is set to resume on 25 March approaching. I do not think it is being unduly cynical to query the publication of this study at the present time as a media event, bearing in mind that it seems to have been carried out five or six years ago.”

This is either again deliberately misleading or an example of conspiracy hysteria. From what I can tell the study was commissioned five/six years ago. Not carried out.

Stone concludes:

Meanwhile, the plight of autistic children with gastro- intestinal symptoms is excluded both from the study and public attention, as if they did not exist. The NAS statement warned of “creating further confusion” and this is precisely what this study and its media exposure has done.

Children with gastro issues and autism were not ‘excluded’ they just weren’t found. Maybe they really don’t exist? Maybe Stone would’ve preferred that the study authors fabricate a few subjects?

The bottom line of this gastro/autism issue is that there is no science to back up the opinion Stone has. On the other hand there is plenty of science that indicates there is no link between MMR and autism. Far from this study creating confusion, it has simply shown up the shortcomings of Wakefield’s bad science and Stone and his ilk are in reality the people desperately attempting to create enough confusion for Wakefield to escape unscathed.

Brad Handley Offers Us A Chance To Evaluate

6 Feb

A couple of days ago, Brad Handley wrote a blog entry on Age of Autism called ‘DR. NANCY MINSHEW & ME: WHO’S CRAZY?’.

Let us instead examine Brad’s criteria for deciding on who is crazy and who is not between Dr Minshew and he.

I disagree with almost every single thing you have written or said about autism. Since we both can’t possibly be right, one of us has to be crazy. I’m scared to death it might be me. As a psychiatrist, I thought you could help.

Says Brad to Dr Minshew in an email. He then continues with:

It is maddening for parents like me that our “experts” can’t agree on the most fundamentally important and critical data point in the entire field of autism: is prevalence truly rising or not? This very binary notion impacts everything else. If it’s growing, it’s the environment. If it’s not, it’s genetics. From you perspective, “The increase in number of cases reflects the increase in recognition of verbal children.” I was confounded by this point, because I can’t find a single sentence in the scientific literature to support this. What I do look to is the following:

OK, lets pause. Brad says there’s no scientific literature to support the idea that there isn’t an epidemic. We’ll come back to that. Firstly, however, he cites a few bits and bobs to support his hypothesis that there is.

First off he cites:

[1]Report to the Legislature on the Principle Findings from The Epidemiology of Autism in California: A Comprehensive Pilot Study MIND Institute, UC Davis, Oct 2002.

This is not in the scientific literature. It is not peer reviewed. According to Brad’s own specified criteria of utilising the scientific literature, he cannot cite this document.

The second (and last) paper he cites is:

[2]National Autism Prevalence Trends From United States Special Education Data. Pediatrics, March 2005. Craig J. Newschaffer, PhD..

Using Special Education data has been debunked in a paper published four months after that Newschaffer paper. The author (James Laidler) says:

Many autism advocacy groups use the data collected by the US Department of Education (USDE) to show a rapidly increasing prevalence of autism. Closer examination of these data to follow each birth-year cohort reveals anomalies within the USDE data on autism……These anomalies point to internal problems in the USDE data that make them unsuitable for tracking autism prevalence.

and Shattuck says:

The mean administrative prevalence of autism in US special education among children ages 6 to 11 in 1994 was only 0.6 per 1000, less than one-fifth of the lowest CDC estimate from Atlanta (based on surveillance data from 1996). Therefore, special education counts of children with autism in the early 1990s were dramatic underestimates of population prevalence and really had nowhere to go but up. This finding highlights the inappropriateness of using special education trends to make declarations about an epidemic of autism, as has been common in recent media and advocacy reports.

So thats the sum total of Brad’s ‘science’ regarding the autism epidemic. A non-science report and a twice debunked study.

Is there actually anything in the scientific literature that suggests the ‘epidemic’ is not anything of the sort?

Variation in the administrative prevalence of ASD is associated with education-related spending, which may be associated with better-trained educational staff who can recognize the problem, and more and better trained in-school specialists who can provide screening. It is also associated with the availability of health care resources. Increased access to pediatricians and school-based health centers may lead to improved recognition of ASD. Interstate variability in the identification of ASD should be taken into account when interpreting the results of prevalence studies based on administrative data and the associated system characteristics taken into account by policy makers working to improve the recognition of ASD.

David S. Mandell, ScD; Raymond Palmer, PhD

The incidence of research-identified autism increased in Olmsted County from 1976 to 1997, with the increase occurring among young children after the introduction of broader, more precise diagnostic criteria, increased availability of services, and increased awareness of autism. Although it is possible that unidentified environmental factors have contributed to an increase in autism, the timing of the increase suggests that it may be due to improved awareness, changes in diagnostic criteria, and availability of services, leading to identification of previously unrecognized young children with autism.

William J. Barbaresi, MD; Slavica K. Katusic, MD; Robert C. Colligan, PhD; Amy L. Weaver, MS; Steven J. Jacobsen, MD, PhD

We observed dramatic increases in the prevalence of autism spectrum disorder as a primary special educational disability starting in the 1991-1992 school year, and the trends show no sign of abatement. We found no corresponding decrease in any special educational disability category to suggest diagnostic substitution as an explanation for the autism trends in Minnesota. We could not assess changes in actual disease incidence with these data, but federal and state administrative changes in policy and law favoring better identification and reporting of autism are likely contributing factors to the prevalence increases and may imply that autism spectrum disorder has been underdiagnosed in the past.

James G. Gurney, PhD; Melissa S. Fritz, MPH; Kirsten K. Ness, MPH; Phillip Sievers, MA;Craig J. Newschaffer, PhD; Elsa G. Shapiro, PhD

Brad continues:

You say vaccines are proven to not cause autism and that parents should vaccinate their children.

Dr. Minshew, you are either being intellectually dishonest on this point or it is outside of your expertise as a psychiatrist to understand the vaccine-autism issue, Let me explain:

Brad _seems_ to be basing this belief on the news article he quotes:

Dr. Nancy Minshew, Director of the University of Pittsburgh’s Center for Excellence in Autism Research, says it’s time to end the debate [about vaccines and autism] because research overwhelmingly proves there’s no connection and parents don’t need to worry about that anymore. Minshew says it’s time real experts dispel the rumors for concerned parents. “They deserve to hear the evidence, the real evidence. So I thought, ‘Enough is enough,'” she said. Minshew says people’s lives are at stake because some kids aren’t getting vaccinated for life-threatening diseases due to incorrect information. Since Thimerosal, an ethyl mercury preservative, was banned from most childhood vaccines in the U.S. seven years ago, autism rates have continued to increase – disproving the link. Minshew says it’s only a coincidence that toddlers are vaccinated around the same time autism is usually diagnosed.

Minshew did _not_ say ‘vaccines are proven to not cause autism’, that is what the article she was quoted in says. You can tell the bits she actually said as they will be surrounded with quote marks.

– Thimerosal was not banned from vaccines as you are quoted as saying, so this is a falsehood.

Minshew was not quoted as saying this. This is a falsehood.

– Thimerosal did not come out of vaccines seven years ago as you are quoted as saying, so this is a falsehood. In fact, it’s still in the overwhelming majority of the flu shot supply at full dose- the flu shot was recently added (2004) to the CDC’s recommended schedule.

Once more, Minshew was _not_ quoted as saying thiomersal came out of vaccines seven year ago. This is a falsehood. Your statement that it is still in the overwhelming majority of the flu shot is speculative and without foundation – unless you have something to back that up….?

And in *fact* – although Minshew never claims it, a CDC meeting reported on a study that said:

N.I.P. estimated the amount of thimerosal in provider vaccine inventories in a survey conducted September 20, 2001 to February 20, 2002. The targets were a convenience sample of providers getting site visits from public health officials across the country. Inventory counts were done of all refrigerators for D.T.a.P., Hib, and hep B pediatric vaccines. The thimerosal classification was based on the lot number information, which was verified by the manufacturers. In September 2001, 225 sites were canvassed, and 447 by February 2002…..During the visits, the providers were surveyed about thimerosal-containing vaccines in their inventories. Of the 447 interviews, 83.5 percent reported no thimerosal-containing vaccines in stock at any time since October 2001.

and

in September 2001, only 5.6%1 of all vaccines contained thiomersal. By Feb 2002, only 1.9% of all vaccines contained thiomersal.

(NB: The 5.6% figure seems to be a typo in the report. It should be 56%. From 33,500 doses out of 63,600; to 2,796 doses out of 149,147)

– If you believe that focusing on a single ingredient in vaccines (mercury) exonerates vaccines in totality, that’s an impossibility. We have grown our vaccine schedule from 10 vaccines in the early 1980s to 36 today. Yet, we never test the “combination risk” of so many vaccines. No one, except Generation Rescue, has ever studied unvaccinated children and looked at their autism rates. We never look at the aluminum that replaced thimerosal, the live viruses, or the many other toxic ingredients in vaccines at all.

So, Brad says that its not just mercury. Which is weird because in Feb 2005 (click the first video) he was saying:

What we immediately realised – and I think this is something that is a surprise to lots of people – um that autism is a misdiagnosis for mercury poisoning. If you line up 100 symptoms of mercury poisoning and 100 symptoms of autism they are exactly the same

So, to borrow a phrase, both can’t be true….is it a misdiagnosis for mercury poisoning or is it the combination of vaccines?

– The parent reports of children going upside-down and developing autism right after vaccination continues unabated. Will you ever listen to them?

People such as Minshew have done nothing _but_ listen. Generation Rescue keep promising something for them to listen to but keep failing to provide it.

Brad continues:

It strikes me, and perhaps I’m crazy for saying this, that now that you have publicly reassured parents that vaccines are safe, that you may well be the last person on earth, even in the face of overwhelming evidence, to concede that vaccines are in fact playing a role in autism.

That, my friend, is called ‘projection’. Now you have publicly hemmed and hawed about what vaccines role is in autism and now all your projections and predictions have singularly failed to materialise (read the rest of that blog entry with the video for details), even with an overwhelming lack of any evidence whatsoever you will be the last person to ever admit you were plain old wrong time and time again.

And yet there’s more.

You never mention recovered children.

In all the writings and quotes of yours, Doctor, I didn’t read one thing about children who have recovered from autism. Have you ever met a recovered child? Would you like to? Would you care to scan their brains and see how they look? I heard a noted neurologist mention an idea that we should scan the brains of children newly diagnosed with autism, let their parents who want to treat the children biomedically, and then re-scan the brains of any children who have recovered. Does that strike you as an interesting idea?

Ah, the famous recovered children. I wrote about this awhile ago. The upshot of it is that when actually looks in detail at the kids Generation Rescue claims as recovered, kids who no longer have a diagnosis account for about 5-7% of the total he presents as recovered. Its a con trick. I even managed to get my own daughter listed as a recovery story on his website.

Brad continues:

As a courtesy, I forwarded the above piece to Dr. Minshew one day in advance of posting it on Age of Autism. What follows is a short email exchange between us:

———————

Dr. Minshew:

What’s written below, by me, will be posted at The Age of Autism blog tomorrow. As a courtesy, I’m sending it to you first.

I have no issues with you personally. In fact, reading that you lost a child makes me very, very empathetic.

That said, it is my heartfelt belief that you are actually part of the problem with autism, rather than part of the solution. I’m sure that’s a comment you disagree with profoundly, but I really believe history will be a harsh judge of scientists like you who continue to deny the existence of a rising prevalence of autism and mistakenly reassure parents that vaccines are safe – a topic you can’t possibly be an expert on, by the way.

I also thought your email to Mr. —- reeked of intellectual arrogance in a very close-minded sort of a way. There are many well-credentialed scientists who would take exception to almost everything you believe about autism, but you speak with sweeping generalizations like you are in the only camp that actually knows where truth lies. I also found your continual reference to a court case in Maryland, while 2 tests cases before the Vaccine Court remain WIDE OPEN, to demonstrate either ignorance on your part or a case of selective fact gathering. What if the test cases in D.C. rule in favor of the plaintiffs?

So, I don’t expect us to be pen pals anytime soon, but I’m including the open letter to you below.

Sincerely,

JB Handley

——————–

From: Nancy Minshew
To: J.B. Handley
Sent: Mon Feb 04 11:50:31 2008
Subject: RE: Nancy & Me: Who’s crazy

Mr. Handley none of you have permission to share emails that i have sent to you as individuals with anyone besides the intended receiver nor do you have permission to quote me publicly. Unlike the newspaper which was public, private emails to individuals sent confidentially are not for public quotation.

——————–

From: J.B. Handley
Sent: Monday, February 04, 2008 11:54 AM
To: Nancy Minshew
Subject: Re: Nancy & Me: Who’s crazy

Says who?

And, tough shit.

J.B. Handley

——————–

Nice guy huh?

And also further example of Brad’s hypocrisy. Our very first online set-to Brad commented (in the comment section) about me publishing part of an email he sent me:

Mr. Leitch sent me an email on my private email account, I responded, and he put my comments on his blog without asking me.

Which wasn’t strictly true but anyway – if I’d known how Brad would chop and change his mind I would’ve just said ‘tough shit’.

Anyway, Brad concludes:

This is my world, Dr. Minshew, it seems clear as day. It’s so different from yours, I really, really need to know: which one of us is crazy?

Lets recap. In Brad’s world science isn’t science unless he says it is. He can chop and change his mind without it invalidating his earlier, contradictory beliefs and its OK to be a massive hypocrite. Are these the actions of a crazy man?

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