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The Truth About Andrew Wakefield

14 Oct

Regular readers will know that an eminent UK scientist writes the occasional guest blog piece for LB/RB. Here is his piece in the wake of the the Lipkin/Hornig study and the amusing claim that it vindicates Wakefield. Enjoy – Kev.

A scientist who has followed the Wakefield saga from the start sets the record straight.

According to recent newspaper reports Andrew Wakefield is planning to publish his account of the MMR/autism controversy next year, under the title The Lesser Truth. He is currently facing charges of gross professional misconduct at the General Medical Council (the case is expected to conclude in April 2009). Meanwhile, Wakefield and his supporters continue to claim that his research is valid and continue to smear the investigative journalist Brian Deer who exposed the conflicts of interest and dubious ethics – as well as the junk science – behind the claims of a link between MMR and autism. But it was Wakefield who was obliged to back down in court from his libel allegations against Deer. Wakefield was unable to contradict Deer’s claim that he has been “unremittingly evasive and dishonest in an effort to cover up his wrong-doing”.

Here are some truths about Wakefield and his research that may not find their way into The Lesser Truth:

Wakefield was never a respected researcher. His first foray into the Lancet was a controversial paper in 1989 saying that Crohn’s disease was due to problems in the blood supply to the gut (vasculitis). But this was wrong. In the early 1990s he was funded by pharmaceutical companies for research along the same lines, mostly in animal models, and produced a series of low-impact, forgettable, papers.

Wakefield first courted notoriety in 1993 when he claimed to have identified measles virus in Crohn’s disease gut tissue. Coincidently, measles virus can cause vasculitis so it is easy to understand how, from 1989 onwards, Wakefield had to find measles in Crohn’s. We now know this result was not possible: there is no measles virus in Crohn’s disease and the antibodies Wakefield used were not specific for measles either. In Wakefield’s own lab, a good molecular biologist, Nicholas Chadwick, could not find measles in Crohn’s by sensitive molecular techniques. However, Wakefield said he could find measles, using crude techniques using flawed reagents. Suppressing data which ruins your hypothesis is scientific fraud.

In February 1996 Wakefield cooked up the idea that MMR was involved in autism with the solicitor Richard Barr and parent activist Rosemary Kessick. He wrote a research protocol to get into the children’s colons to look for measles virus and gut damage, and applied to the Legal Aid Board for £55K.

By October 1996, the Royal Free team had scoped enough children to provide Wakefield with tissue samples so that his technician could look for measles virus in the guts of autistic children by immunohistochemistry. This was clearly research, without clinical or ethical justification.

By spring/summer 1997 Wakefield had enough cases and enough creative data for his story. He believed that autistic children had gut inflammation and most importantly, he believed that he had discovered the cause – measles virus persisting in the gut from MMR. Wakefield first tried to get this study published in Nature but it was rejected.

Towards the end of 1997 he sent an abstract of this work to be presented at Digestive Diseases Week in the USA in May 1998. He also submitted two papers to the Lancet. The first was accepted and published as the now notorious February 1998 Lancet paper. The second, the study claiming to have identified measles virus in the gut by immunohistochemistry, was rejected. To see Wakefield’s pictures of measles virus in the guts of autistic children go here (slides 37 and 38). The second paper was never published and has now mysteriously disappeared, although Wakefield showed it all over North America for years.

In 2000, Wakefield published a larger series on “autistic enterocolitis”, the new disease he claimed to have identified (Wakefield et al 2000 Enterocolitis in children with developmental disorders. American Journal of Gastroenterology 95: 2285-95). Analysis of the data in this paper has revealed that it was a scam: autistic children do not have a chronic inflammatory bowel disease. Normal findings in children were called pathology, pathological results were re-examined and sexed up, and new abnormalities were manufactured, all to make it appear that these children had gut inflammation (MacDonald TT, Domizio P. Autistic enterocolitis; is it a histopathological entity? Histopathology. 2007 Feb;50(3):371-9).

As the litigation in the UK began to heat up around 2000, the defendants (the MMR manufacturers) started to ask simple questions, such as, where is the paper which shows measles in the gut of autistic children? This was part of the MMR/autism story that was rejected by Nature and the Lancet. Who knows why Wakefield never published it? Maybe he realised it was junk since at the same time his identification of measles virus in Crohn’s disease had unravelled. Maybe he knew that the experts for the defence had looked at the data and the methodology and shown it was junk.

Wakefield now hooked up with Dublin pathologist John O’Leary. O’Leary was supposedly an expert in an unsound and discarded methodology called in cell PCR, which he claimed allowed him to amplify measles genetic material in tissue samples, in this case, from the guts of children with autism, and identify its cellular location. He also set up PCR techniques to amplify measles from samples of gut. The O’Leary lab’s studies of Wakefield’s gut biopsy specimens were published in another notorious paper (Uhlmann et al. Potential viral pathogenic mechanism for new variant inflammatory bowel disease. J Clinical Path: Mol Pathol 2002;55: 84-90).

In his testimony to the Omnibus Autism proceedings in Washington in summer 2007, London-based molecular biologist Professor Stephen Bustin showed the utter incompetence of O’Leary and his lab. He revealed the fact that a result was called positive if the sample contained measles virus but no DNA (a biological impossibility). He also revealed that if they analysed the same autistic sample 6 times and got a positive once, the patient was deemed to be positive, even though they were also getting positive measles results out of samples of pure water.

It seems that O’Leary has belatedly seen the error of his ways: in the recently published Hornig study, his lab – in common with other labs in the USA – failed to find measles in samples from autistic children (Hornig et al 2008 Lack of association between measles virus vaccine and autism with enteropathy: a case-control study. PLOS One 3(9):e3140). The attempts by Wakefield and his acolytes to claim that the Hornig study vindicates the Uhlmann paper are preposterous. Distancing himself from Wakefield as fast as is possible for any man of 20 stone, O’Leary cleaned up his lab and did things properly.

A review of the career of Andrew Wakefield is a trawl through the underbelly of science. Wakefield did not do experiments to seek the truth – he did experiments to confirm his own beliefs. He produced junk science for over a decade and did immense damage to patients with Crohn’s disease, and autistic children and their parents. Hopefully the GMC will nail the charlatan, and show some sympathy for the Royal Free clinicians who thought Wakefield was honest. The Andy Wakefield show has now moved to the USA where he can get the attention he craves and he can play the role of the selfless seeker of truth whom the establishment had to silence. Being a victim is a good career move for him. It will help Thoughtful House sell junk therapies for autism to desperate parents and allow Andy to live in a really big house, where he can entertain his showbiz friends. He really wanted to be a famous scientist, but he was rubbish at that, so he had to become (in)famous by other means.

The exoneration of John O'Leary

5 Sep

Since the publication of the latest MMR study to refute any connection to autism, the principal believers in the idea that vaccines _simply must_ have some connection to autism have been floundering to spin some positives from the study. They have decided to concentrate on getting this study to exonerate Unigenetics (the lab of Professor John O’Leary). A little backstory is necessary here.

The idea that MMR leads to autism was first perpetuated by Andrew Wakefield. The idea goes that the MMR is injected, the measles component travels to the gut where it persists and causes severe gastric issues. It travels on to the brain and causes autism. Hence, it is – in the Wakefield scenario – the measles virus component of the MMR that causes autism.

In order to test this hypothesis, Wakefield tested for the presence of measles virus in the gut of autistic kids and lo and behold found loads. The way he found them was to send his biopsy samples off to the lab of John O’Leary, Unigenetics, in Dublin. Unigenetics ran the tests on the Wakefield samples and reported they had found measles RNA in significant percentages in Wakefield’s samples. They tested the samples using a technique called PCR.

So, later on, as study after study failed to replicate Wakefield’s – except, tellingly, for studies that went through Unigentics – investigators became suspicious of the results being generated at Unigenetics. As part of the UK litigation into MMR Professor Stephen Bustin – quite possibly _the_ world expert in PCR – went in and spent over 150 hours examining the methods used at Unigenetics to get their results. What he found was a bombshell.

Two things clearly arose from Bustin’s investigation. The first was a clear error of methodology. They forgot to perform an ‘RT Step’. What this was and what it meant is cleared up nicely here by commenter Brian:

The RT stands for “Reverse Transcriptase”, an enzyme that makes a DNA copy of an RNA molecule.

Measles virus exists as an RNA molecule. The polymerase chain reaction (PCR) assay amplifies DNA. Thus to detect an RNA molecule in a PCR assay, the RNA must first be copied (by the reverse transcriptase enzyme) into DNA, which can then be amplified.

Bustin showed that the O’Leary lab reported positive results even when they could not possibly have detected an RNA molecule because they had left out the step to copy that RNA into DNA. Thus the positive results reported for such assays were undoubtedly false positives.

Its worth noting here that Bustin found this methodological error by following Unigenetics lab manual if I recall correctly.

Here is Bustin himself:

If you detect a target that is _apparently_ measles virus in the absence of an RT step by definition it can’t be measles virus because it has to be DNA [measles virus does not exist as a DNA molecule]. It’s a very simple concept. At least it is to me. It’s not to everyone else.

So what were they reporting as measles virus? Lab contamination. That was the second error.

OK, so now back to today and the new MMR paper and the drive to make it exonerate O’Leary.

The new study used three labs to perform its detection. All three performed excellently. One of the labs was (you guessed it) John O’Learys in Dublin.

So, two new press releases have hit since then. I’ll quote from them both.

This is from Thoughtful House (Andrew Wakefield’s Texan fiefdom):

This new study confirmed that results from the laboratory of Professor John O’Leary….were correct, and identical to the results obtained by the laboratories of the Centers for Disease Control and Prevention (CDC) and Dr. Ian Lipkin of Columbia University.

In that this new study affirms the reliability of Professor O’Leary’s laboratory and therefore of his previous findings, a major impact upon the current hearings in vaccine court is likely, wherein the government’s defense relies largely on the claim that Professor O’Leary’s finding of measles in the intestinal biopsy of Michelle Cedillo (a child with severe autism and epilepsy) was unreliable. The historical reliability of the measles assay used in Professor O’Leary’s laboratory is now confirmed.

And SafeMinds:

One of the three labs involved in the Hornig study was led by John O’Leary who conducted the testing for the Wakefield study. The three Hornig study labs validated each other,
confirming the rigorousness of Dr. O’Leary’s work. Dr. O’Leary conducted the testing for one of the autism test cases now in the Federal Court for Vaccine Claims. The child, who regressed into autism
and bowel disease after receiving the MMR, tested positive for measles virus.

So, you can see that this is the spin – exonerating Unigenetics work that Stephen Bustin had demolished.

They take a rather simplistic viewpoint of things – that because the lab performed well now, it did then. I think that’s rather a large assumption.

I also think that they have forgotten the timeline of events surrounding the Cedillo case.

Michelle Cedillo’s positive measles virus finding was in 2002:

From the cross examination of Arthur Krigsman:

Q: OKay, now in support of your opinion that Michelle has persistent measles virus in the lymphoid tissue of her bowel, you cite to the positive finding in *2002* by the Unigenetics in Dublin, Ireland of measles RNA in the tissue sample tested in Michelle, correct?

A: By the published report, of their findings.

Q: But from Unigenetics, specific to Michelle?

A: Right.

(Page 531, line 9 – 18)

Stephen Bustin did not enter the lab until January 2004.

From the Direct examination of Stephen Bustin:

Q:…..Now, you were granted physical access to the Unigenetics laboratory?

A: I was, yes.

Q: When?

A: In January 2004 and then again in May 2004.

(Page 1964, line 12 – 16)

In other words, Michelle Cedillo’s test results were generated by Unigenetics, _before_ Stephen Bustin (or anyone else) had discovered the catastrophic errors that made it impossible they were detecting measles.

The question becomes – if you were John O’Leary and someone had made it perfectly clear that you had done bad work two years earlier would you then carry on missing out the RT step? Or would you not? By the time 2008 rolled around, would you hope that your lab staff could do their jobs properly? Or wouldn’t you really care?

The idea that this new MMR study somehow exonerates the work of Unigenetics prior to 2004 is a joke. Unfortunately, Michelle Cedillo’s testing was done prior to 2004. Two years prior, back to a time when Unigenetics weren’t so good at lab work.

MMR still doesn't cause autism

3 Sep

In shocking news, yet another study shows that the MMR doesn’t cause autism. The study (which is here for your edification Dear Reader).

attempted to replicate 1998 research by a team led by Dr. Andrew Wakefield, then of Britain’s Royal Free Hospital, in the Lancet medical journal that suggested the vaccine was linked to autism and gastrointestinal problems.

And how did that work out for them?

….they could not find any link and hope their study will encourage parents to vaccinate their children to combat a rash of measles outbreaks.

The ‘official’ study conclusion is:

This study provides strong evidence against association of autism with persistent MV RNA in the GI tract or MMR exposure. Autism with GI disturbances is associated with elevated rates of regression in language or other skills and may represent an endophenotype distinct from other ASD.

Interestingly, the lead author is one Mady Hornig whom you might remember from the infamous Rain Mouse debacle. Seems like she’s turned over a new leaf. Gone are the lurid descriptions of skull chewing and in instead are pleas to vaccinate children from a killer disease. Credit where its due Ms Hornig, well done.

“We found no relationship between the timing of MMR vaccine and the onset of either GI complaints or autism,” Dr. Mady Hornig, also of Columbia, said in a statement.

Another interesting aspect is that the methodology the team used means they utilised three different labs. One of which was the O’Leary lab. This time, they did a good job. Shame they screwed up so bad the first time. Maybe if they hadn’t, things would’ve been over a long time ago. Is it just me or does this paper feel like a few people trying to claw back some scientific credibility?

Anyway, the study also found:

But the study did find evidence that children with autism have persistent bowel troubles that should be addressed.

They still didn’t say whether these bowel troubles (which they found weren’t associated with the MMR) were occurring at a higher rate in autistic kids. Maybe someone will address that one day.

Oh and Rick Rollens was there too, teeth and buttocks clenched no doubt as he congratulated the scientists. He said:

No longer can mainstream medicine ignore parents’ claims of clinically significant GI distress.

Had they ever? I’ve never seen a study that shows that. He also said:

“This study by itself does not exonerate the role of all vaccines”

What a genius. He spotted the phrase ‘Measles Virus Vaccine’ in the study title and worked out the rest all by himself! Nothing gets past our Rick!

So, MMR doesn’t cause autism. No news and of course won’t convince the flat earthers but still – another welcome addition to the ever growing canon of evidence against MMR causation.

Further Reading Elsewhere
Mike at Action For Autism
Kristina at AutismVox
Anthony at Black Triangle
Orac at Respectful Insolence
Steve at One Dad’s Opinion
Phil at Bad Astronomy

Leaky gut aka intestinal permeability

18 Aug

Leaky Gut syndrome is a hypothesis associated with autism by people who believe that toxins (particularly those caused by vaccines – notably the MMR) weakens the lining of the bowel letting various rubbish thorough (undigested food, toxins, whatever) and triggering an immune response and/or leading to Wakefield’s much-hyped but never backed up Autistic Enterocolitis.

This unverified condition has (of course) been found by any number of Wakefield supporters and yet, curiously, no researchers external to Wakefield’s peers have found any evidence for it and the phrase exists as a diagnosis within that AltMed community.

In fact, its not curious at all as the only groups that _did_ find evidence for ‘Autistic Enterocolitis’ used the now discredited Unigentics lab run by John O’Leary.

Anyway, in Feb of this year a team from the University of Calgary published a Pilot study into the ‘leaky gut’ (posh name: ‘intestinal permeability’) issue.

They enrolled 14 autistic kids (all of whom had parents who reported gastric issues), 7 NT siblings of these kids, and 8 NT non-related controls.

In the ‘leaky gut’ opioid-excess theory, it is proposed that increased intestinal permeability in children allows for increased absorption of dietary peptides, which ultimately leads to disruption of neuroregulatory mechanisms and normal brain development.

The reason for choosing autistic kids who were reported by parents to have gastric issues is that the researchers reasoned that these kids would be more likely to have ‘abnormal gastrointestinal tests’.

In this population, the researchers found:

we neither demonstrate abnormal small intestinal permeability, nor abnormal postprandial responses of the enteroendocrine peptide GLP-2.

…..

It has been suggested that increased permeability may be causally related to the onset of the inflammatory bowel disease and not just a consequence of inflammation. Our data does not support a similar hypothesis in autism.

…..

Our study did not detect differences in the functional gastrointestinal parameters measured in a group of children with autism. Although there may be a subset of children with autism with a specific gastrointestinal abnormality there is no firm evidence yet of a role for gastrointestinal dysfunction in
the etiology of autism.

One of the things the authors reported that struck me was:

The subtle endoscopic and histological findings of lymphonodular hyperplasia in the colon and ileum previously described in ‘‘autistic enterocolitis’’ (Wakefield et al. 1998, 2005) are also seen in normally developing children with similar gastrointestinal symptoms (Furlano et al. 2001).

This is only a pilot study of course so not too much can be read into the results but if the study is expanded upon and replicated then the results would be interesting to see. Its certainly a smallish spanner in the works of the ‘autistic enterocolitis’ believers.

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