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Adverse Effects of Vaccines: Evidence and Causality

26 Aug

The United States Institute of Medicine (IOM) has just published a lengthy report, Adverse Effects of Vaccines: Evidence and Causality.

The short summary, via Reuters, is: “the big take-home message is that we found only a few cases in which vaccines can cause adverse side effects, and the vast majority of those are short-term and self-limiting.”

As to autism? There are two main theories of autism and vaccines: MMR and Thimerosal. The autism and MMR theory is one of the most studied and most clear. The committee found that the research “Favors Rejection”. As in,

The committee concluded the evidence favors rejection of five vaccine-adverse event relationships. These include MMR vaccine and type 1 diabetes, DTaP vaccine and type 1 diabetes, MMR vaccine and autism, inactivated influenza vaccine and asthma exacerbation or reactive airway disease episodes, and inactivated influenza vaccine and Bell’s palsy. The evidence base for these conclusions consisted of epidemiologic studies reporting no increased risk; this evidence was not countered by mechanistic evidence

The epidemiological evidence says there is no increased risk. There is no good mechanism known or postulated whereby MMR could cause autism.

Thimerosal is barely mentioned in the report, with only 7 mentions. As far as autism+thimerosal is concerned, the IOM reviewed the literature years back and found no evidence of a link. Since that time, the evidence has grown greater against a link and thimerosal has been removed from the routine pediatric vaccine schedule (e.g. Price et al. Prenatal and Infant Exposure to Thimerosal From Vaccines and Immunoglobulins and Risk of Autism
and, while not specific to autism, Thomson et al. Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years)

Previous IOM reports on Thimerosal: Immunization safety review: Thimerosal -containing vaccines and neurodevelopmental disorders.

Previous IOM report on vaccines and autism (especially MMR and thimerosal): Immunization safety review: Vaccines and autism.

I expect much criticism to be focused on the IOM from some circles. The arguments will likely focus on “look at all the vaccines which have not been specifically studied in relation to autism”. It is a semi valid point. The problems with the argument are many, but include: what mechanism is there for these vaccines to cause autism? (Too many too soon is a slogan, not a scientific argument). Without a mechanism, and without some sort of data showing a possible link, there is such a low possibility of finding anything that resources are best spent elsewhere. In addition, the studies to date give a reasonable proxy for vaccine exposure: the more thimerosal an infant was exposed to, the more vaccines. Thimerosal exposure becomes a proxy for the number of vaccines. It has been shown (multiple times) that there isn’t an increased risk for autism with thimerosal.

Lastly, if you read the criticisms claiming “but they’ve only studied one vaccine and one ingredient”, watch for the intellectual honesty. That’s the part where the critic admits that “they’ve only studied one vaccine and one ingredient, and they found that those don’t increase the risk of autism“. Most critics in this field are cake-eaters. They want their cake (the argument that the studies have only looked in depth at MMR and thimerosal) and they want to eat it too (by denying the results of those studies). It’s predictable.

The Measles Initiative and the myth of mild measles

9 Jul

Advance warning: this post has basically nothing to do with autism. It is about a group called the Measles Initiative. I found the site for the Initiative while looking for information about the effects of measles in the non-developing world. There have been outbreaks in France, for example, in recent years. Large enough outbreaks that people have died.

Here is a figure from a presentation given by Daniel Floret of the Claude Bernard University Lyon and Chairman of the French NITAG and of the French Working group on measles elimination.

Yes, even in modern times, in developed countries like France, measles can kill. Unfortunately, segments of the autism communities play an active role in disseminating the misinformation about measles (downplaying the risk) and the vaccine (inflating the risk).

One thought: you’ve probably seen groups and people on the net claiming that the developing world doesn’t need vaccines. Clean water and/or improved sanitation they say, will suffice. Of course, we would all like to see better water and sanitation worldwide. But next time you see that argument posed, ask yourself, “Has this group ever advocated for or raised money to improve the water or sanitation anywhere?”

In the past 10 years there has been a major initiative to increase vaccination rates in Africa. This has had a major impact, with measles deaths dropping by 90%. The World Health Organization announced the success of this effort in a press release, Measles deaths in Africa plunge by 91%.

Measles deaths in Africa fell by 91% between 2000 and 2006, from an estimated 396 000 to 36 000, reaching the United Nations 2010 goal to cut measles deaths by 90% four years early. The spectacular gains achieved in Africa helped generate a strong decline in global measles deaths, which fell 68% worldwide – from an estimated 757 000 to 242 000 – during this period.

Unfortunately there hasn’t been a strong focus on measles reduction in South Asia, and measles deaths have not changed. The following image shows that as the number of deaths have dropped in Africa, they have not dropped in south Asia.

It really bothers me that so much of the bad information about vaccination comes from a segment of the autism communities. It bothers me that this misinformation puts people at risk. There is a real risk of injury and death, even in the developed world as we can see from the data from France. Measles vaccines work. They prevent deaths. And, while I haven’t gone into it in this discussion, the MMR-causes-autism notion has been tested carefully and it is wrong.

Four Somali children die of measles

5 May

Dr. Abdirahman D. Mohamed, the chief of staff at Axis Medical Center in Minneapolis, said last month he knew of four unvaccinated Somali children who had died from measles.


This appalling news comes hot on the heels of anti-vaxxer conspiracy theorist Andrew Wakefield’s visit to the Somali community in the US to promote his fraudulent anti-MMR ‘studies’. Generation Rescue has also attended to the Somali community in Minneapolis.

Antivaccine groups have noticed. In November, J. B. Handley…wrote an open letter to “Courageous Somali Parents.”

He warned them not to trust the state health department and suggested they slow down their children’s shots and get exemptions to school vaccination requirements. He also offered to pay for some to attend an antivaccine conference.

All these people and groups should now reap the harvest of what they have sown. Death. Preventable death.

No association between early gastrointestinal problems and autistic-like traits in the general population

28 Mar

Gastrointesintal problems are a common topic of discussion and debate in the online autism communities. Much of the discussion involves causation: do GI problems cause autism? A recent study looks at a tangent of this argument. Considering the general population, do GI problems early in life predict autistic traits later in life? The methodology isn’t the strongest: they use parent reports of GI complaints and the self-report questionaire Autism Quotient. They also asked about whether the individuals were immunized with the MMR vaccine.

The results:

There was no statistically significant difference in AQ scores between those who had (n=133) and those who had not (n=671) experienced early gastrointestinal symptoms. (2) analyses revealed that the children with early gastrointestinal problems were no more likely to be represented in the upper quintile of scores on any of the AQ scales. The measles, mumps, and rubella vaccination was unrelated to gastrointestinal symptoms or AQ scores.

The abstract is quoted below:

No association between early gastrointestinal problems and autistic-like traits in the general population

The aim of this study was to determine whether gastrointestinal problems in early childhood relate to autistic-like traits in a general population sample.

The parents of 804 children (442 females; 362 males) reported at 1-, 2-, 3-, and 5-year follow-ups whether their child had been taken to a hospital, general practitioner, or health clinic for any of five gastrointestinal symptoms: (1) constipation; (2) diarrhoea; (3) abdominal bloating, discomfort, or irritability; (4) gastro-oesophageal reflux or vomiting; and (5) feeding issues or food selectivity. Parents also reported whether their child had received the measles, mumps, and rubella vaccination. Autistic-like traits were measured when the children had reached early adulthood (mean age 19y 7mo; SD 0.63y) using a self-report questionnaire, the Autism Spectrum Quotient (AQ).


There was no statistically significant difference in AQ scores between those who had (n=133) and those who had not (n=671) experienced early gastrointestinal symptoms. (2) analyses revealed that the children with early gastrointestinal problems were no more likely to be represented in the upper quintile of scores on any of the AQ scales. The measles, mumps, and rubella vaccination was unrelated to gastrointestinal symptoms or AQ scores.


Parent-reported gastrointestinal problems in early childhood are unrelated to self-reported autistic-like traits in the general population.

Sloppy science – a perfect example of how the anti-vaccine crowd will listen to anything

11 Feb

Both Age of Autism and David Kirby have recently reported on a new review paper with Age of Autism describing it as ‘pretty interesting’ and David repeating a part of the abstract:

Documented causes of autism include genetic mutations and/or deletions, viral infections, and encephalitis following vaccination.

So, should we all in the skeptic camp be reaching for our humble pie and our knife and fork? Not exactly. Lets take a look at the contents of this paper. Lets start here:

The vaccine organism itself could be a culprit. For example, one hypothesis of the cause of autism is that the pertussis toxin in the DPT vaccine causes a separation of the G-alpha protein from retinoid receptors in genetically at-risk children (Farfel et al., 1999; Megson, 2000). The pertussis toxin creates a chronic autoimmune monocytic infiltration of the gut mucosa lamina propia and may disconnect the G-alpha protein pathways, leaving some G-alphamodulated pathways unopposed. In turn, the non-specific branch of the immune system is turned on and, without retinoid switching, cannot be down regulated.

Wow, blinded with the cool science yet? No, me neither. Go back to line one where it says ‘one hypothesis’. All that follows from that point is mere opinion. There’s no science to back it up.

Another organism of suspect is the live measles virus…

Yeah except its really not. The issues with the Wakefield hypothesis are so many and so thoroughly debunked, it really isn;t worth my time or yours going through them again and again.

There is evidence that Thimerosal (which is 49% ethyl mercury) is indeed harmful. Since the 1930s, Thimerosal has been extensively used as an antibacterial agent in vaccines (Geier et al., 2007). Thimerosal has been implicated as a cause of autism. Not only is every major symptom of autism documented in cases of mercury poisoning but also biological
abnormalities in autism are very similar to the side effects of mercury poisoning itself (Bernard et al., 2001)

Oh dear. Reliance on more thoroughly debunked rubbish in the form of well, anything by the Geier’s and the ridiculous Bernard ‘paper’. I’m happy to go through why these are rubbish but I think I’d be preaching to the converted.

The rest of the paper is a rogues gallery of debunked and fringe science. Helen Ratajczak cites the Geier’s numerous times, DeSoto and Hitlan, Nataf and Rossignol to name but a few. This isn’t a paper so much as an advert for the sort of poor science that was examined in the Autism Omnibus proceedings and roundly rejected by the Special Masters. For goodness sake, she even cites David Ayoub of the Black Helicopter infamy.

When it comes to this paper – handle with extreme caution. Its toxic rubbish.

Salon retracts RFK Jr. article

16 Jan

In 2005, Salon published online an exclusive story by Robert F. Kennedy Jr. that offered an explosive premise: that the mercury-based thimerosal compound present in vaccines until 2001 was dangerous, and that he was “convinced that the link between thimerosal and the epidemic of childhood neurological disorders is real.”

The piece was co-published with Rolling Stone magazine — they fact-checked it and published it in print; we posted it online. In the days after running “Deadly Immunity,” we amended the story with five corrections (which can still be found logged) that went far in undermining Kennedy’s exposé. At the time, we felt that correcting the piece — and keeping it on the site, in the spirit of transparency — was the best way to operate. But subsequent critics, including most recently, Seth Mnookin in his book “The Panic Virus,” further eroded any faith we had in the story’s value. We’ve grown to believe the best reader service is to delete the piece entirely.

“I regret we didn’t move on this more quickly, as evidence continued to emerge debunking the vaccines and autism link,” says former Salon editor in chief Joan Walsh, now editor at large. “But continued revelations of the flaws and even fraud tainting the science behind the connection make taking down the story the right thing to do.” The story’s original URL now links to our autism topics page, which we believe now offers a strong record of clear thinking and skeptical coverage we’re proud of — including the critical pursuit of others who continue to propagate the debunked, and dangerous, autism-vaccine link.

Well done Salon.

Why does it matter what happens to Andrew Wakefield?

8 Jan

People have been questioning the necessity of these latest revelations about Andrew Wakefield and suggesting that enough is enough or maybe that all this latest round of publicity will do nothing except make him a heroic martyr. This is possible.

However, for a number of reasons I really feel it is vitally important that not only is there some response but that that response comes at least partly from the autism community.

Firstly, I believe it is necessary for there to be a response full stop. These might be the same set of _facts_ that were uncovered during the GMC hearing but the difference here is that for the first time it has been established that the facts against Andrew Wakefield came about through what the BMJ refer to as fraudulent. This is a huge difference. Up until now it could’ve been argued that Andrew Wakefield simply made a mistake. After the events of the last two days, that can never be honestly argued again.

Secondly, there are a set of people who have been at the rough end of Wakefield’s fraud for the last 13 years. A set of people who have struggled to make new parents understand that there is no risk of autism from the MMR vaccine. Doctors. Particularly paediatricians and GP’s. It is vital that by establishing what Wakefield has done as fraud, the media ensure that the message is spread far and wide. They (the media) have something to atone for in this respect, being the original spreaders of the message that the MMR caused or contributed to autism. They now need to recognise their role in the past and help the medical establishment by ensuring Wakefield can never again spread his fraudulent claims via their auspices.

Thirdly, there is another set of people who have been at an even rougher end of Wakefield’s fraud. The sufferers of the falling vaccination rates of MMR. Its been well documented in numerous places, including this blog how people – particularly children – have been injured and died in the UK and US. The concept of herd immunity, no matter what some might claim is a real concept and when it falls, the level of protection falls. When it falls to far then the people who suffer are the very young, the very old and those who for genuine medical reasons cannot be vaccinated. Wakefield’s fraud needs to be spread far and wide in order for people to realise what he is, what he tried to do and what the consequences were in order to have some confidence in the MMR jab.

Fourthly, there is another set of people who have suffered heavily. This set of people are the silent victims of Wakefield’s perfidy. Autistic people. Wakefield and his supporters, TACA, NAA, Generation Rescue, SafeMinds, Treating Autism et al have turned autism into a circus. The aim of the last decade amongst serious autism researchers and advocates has been to

a) Raise awareness
b) Find evidence-based therapies that will help the life course and independence of autistic people
c) Protect the educational rights of autistic people

and getting research monies to meet these aims is long, hard and slow. Andrew Wakefield and his hardcore of scientifically illiterate supporters have actively derailed that process, dragging research monies away from these principled activities and towards their core aim of degrading vaccines and ‘proving’ vaccines cause autism. Wakefield himself has taken over US$750,000 worth of money to pursue a legal battle against the UK Gvmt. Just think of how that money could have enriched the life of just one autistic person.

However, this same set of people claim to be representative of the autism community. They write nonsense books about autism. They hold celebrity studded fundraisers for autism. They participate in rant-filled rally’s for autism. But none of them are really about autism. What they’re about is anti-vaccinationism.

Every one of these activities denigrate autism and autistic people. They take attention away from where it is needed.

We, the true autism community, made up of parents, autistic people, professionals of autistic people need to do two things. Firstly, we need to wrest back control of the autism agenda from these one-note people. Secondly, we need to speak to society at large and say ‘yes, some members of the autism community believed the fraudulence of Andrew Wakefield but not all of us did. Please don’t tar us all with one brush.’

What Andrew Wakefield has done has impacted everyone. We need to make sure that he and people like him can never affect us all in this way again. To do that we need to speak out about him, loudly and as long as it takes.

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

4 Sep

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

The Cedillo Appeal

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

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

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

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

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

From the appeals court decision:

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

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

A few points to be made here.

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

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

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

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

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

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

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

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

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

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

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

The appeals court disagreed:

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

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

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

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

Dr. Andrew Wakefield to join Dr. Arthur Krigsman in clinic independent of Thoughtful House?

20 May

Dr. Andrew Wakefield gives an interview in a recent story in the Austin Statesman, Censured doctor says he’ll resume autism research in Austin.

Dr. Wakefield is the primary doctor behind the idea that the MMR vaccine causes autism. His initial paper suggesting this link has been retracted by The Lancet, and the General Medical Council ruled that he was dishonest in his research efforts and showed a callous disregard for his subjects. He expects to lose his license when the GMC finishes the second phase of their action against him next Monday.

According to Dr. Wakefield, this will be the “final effort by the mainstream medical establishment to silence him and stop his research.”

I am at a loss for how this could silence him or stop his research. Dr. Wakefield resides in the United States and has for some time. Even when he was doing research in the United Kingdom, he was not working in a capacity to use his medical license (at least to my understanding).

The interview continues–

“Now that they have come to their determination, I will make absolutely sure the truth comes out,” Wakefield said. “I think I am in a position to encourage people to take a more serious look at the kinds of projects I am considering,” such as researching the long-term health of children who have been vaccinated and those who have not been vaccinated.

Again, I am at a loss. Why has Dr. Wakefield waited until he lost his license, something which he does not use, to make sure that the truth comes out? I would also question whether he is in a position to be taken seriously.

Dr. Wakefield is further quoted:

“Vaccine safety is built upon the confidence of the public u2026 and I’m not prepared to (compromise) that,” he said Wednesday, adding that he hopes people will read the book and “make up their own minds about what is real and what isn’t real.”

Dr. Wakefield is not prepared to compromize the public’s confidence in vaccines?

I am, yet again, at a loss for words.

On the subject of Dr. Wakefield’s future efforts:

Wakefield said he resigned from Thoughtful House so he wouldn’t be a distraction from its work. He said Thoughtful House was getting away from a focus on gastrointestinal issues and autism. Krigsman posted a message to former Thoughtful House patients saying their records would be forwarded to him, and they could see him at a “new, independent” office in Austin where Wakefield said he would do research similar to what he did at Thoughtful House.

Brian Deer discusses Andrew Wakefield’s “autistic enterocolitis” in the BMJ

15 Apr

Before the General Medical Council reached a verdict on Dr. Wakefield, Brian Deer was promising that he was going to report on the data Dr. Wakefield used for his now retracted Lancet paper. We were told that he would give a first time ever view of a journalist allowed to check the facts on a scientific research paper.

After the GMC verdict was handed down, I watched the Sunday Times for such an article. I waited. Well, the wait is over. And it isn’t in the Times. Mr. Deer reports his findings in the British Medical Journal (BMJ).

Although much of the attention on Dr. Wakefield’s work has centered on the possible MMR connection, the topic of a “new syndrome” called “autistic enterocolitis” was proposed in that paper. In Wakefield’s “autistic enterocolitis” under the microscope, Mr. Deer takes a closer look at that claim. He does what is very rarely done: he obtained original data used for the study and obtains expert opinions on that data.

In his introduction, he notes the “new syndrome” and the MMR angles of the Lancet paper. Citing the press release from the Lancet paper:

“Researchers at the Royal Free Hospital School of Medicine may have discovered a new syndrome in children involving a new inflammatory bowel disease and autism,” the institution announced in a press release in February 1998. “Their paper . . . also suggests that in a number of cases the onset of behavioural symptoms was associated with MMR vaccination.”

Mr. Deer notes that before any patients were investigated, Dr. Wakefield was already proposing in a submission to the Legal Aid Board that such a new syndrome exists and it is linked to regression in children.

“In contrast to the IBD cases, which have a prima face [sic] gastrointestinal pathology, children with enteritis/disintegrative disorder form part of a new syndrome,” said Wakefield and the lawyer in a confidential submission for legal aid funding for the project in June 1996, before any of the 12 children in the paper had been investigated. “Nonetheless, the evidence is undeniably in favour of a specific vaccine induced pathology.”

For emphasis:

The evidence was “undeniably in favour of a specific vaccine induced pathology”.

Before children were investigated.

That on its own is huge. And, from what I can tell, not consistent with the image Dr. Wakefield is portraying in the alternative media.

That said, was there evidence of this “new syndrome”?

But when the children were brought in to the Royal Free for ileocolonoscopy, between July 1996 and February 1997, a snag in Wakefield’s project emerged. The hospital’s pathology service repeatedly judged colonic biopsy samples to be unexceptional, and thought bowel disease was a possibility in only one child.

The Royal Free’s own pathology service thought that the biopsy samples were unexceptional.

How can Mr. Deer make such a claim? He obtained data from the children’s records from their investigations at the Royal Free. Unfortunately, the actual samples are no longer available, but the reports are, and Mr. Deer submitted these to experts to review:

The biopsy slides are no longer available, according to one of the paper’s authors, Professor Amar Dhillon, but the GMC obtained all but one of the hospital pathology reports, and for the missing case I obtained the discharge summary. I passed the summary and reports to specialists for their reaction. They concluded that most of the 11 children reported as having non-specific colitis in the Lancet paper had been reported by the Royal Free as having normal pathology.

One expert reviewer stated:

“In the present reports and patients, overall, it is my impression that 8 of the 11 [for whom pathology reports were available] were normal,” Karel Geboes, a professor in the gastrointestinal pathology unit of the Catholic University of Leuven, Belgium, told me.

How does this compare to what was reported in the Lancet?

Eleven of the 12 children were said to have “non-specific colitis”: a clinically significant inflammation of the large bowel. In all 11, it was said to be “chronic,” while in four it was reported as both “acute and chronic.”

In other words, the report in the Lancet is not consistent with how experts interpret the pathology reports.

Mr. Deer further notes:

In fact the [Royal Free’s pathology] service identified findings suggestive of possible inflammatory bowel disease in only one of the 12 children. “The mild patchy generalised increase in inflammatory cells with lymphoid aggregates and follicles is not very specific but could be in keeping with low grade quiescent inflammatory bowel disease,” it reported for child 2. But this inflammation resolved after two months’ enteral feeding with a product now marketed as Modulen. A repeat ileocolonoscopy found no abnormality, and a food intolerance was diagnosed.

Yes, it appears that the pathology service, at Dr. Wakefield’s own hospital, at the time of the investigation, didn’t find evidence of abnormalities reported by Dr. Wakefied’s team.

In the GMC hearing, one of the co-authors on the Lancet paper, Dr. Susan Davies, discussed her concerns about the changes in the findings from normal to abnormal at the time of the investigation.

These changes—from normal to abnormal, or from healthy to diseased—had also raised concern in the mind of at least one of the paper’s authors. In September 2007, Davies, the lead histopathologist for the Wakefield project, was examined at length before the panel. “When you were given a draft of the Lancet paper, did you read it?” she was asked by Sally Smith QC, for the doctors’ regulator.
“Yes,” Davies replied.
“What was your overall view of the terminology used in relation to the histology findings in the Lancet paper, just when you read the paper?”
“I was somewhat concerned with the use of the word colitis.”
“First of all, what did you understand that word to mean?”
“I personally use that terminology, ‘colitis,’ when I see active inflammation, or a pattern of changes which suggest a specific diagnosis, and it was not my impression that the children coming through in the spasmodic way that they had, I [sic] had formulated some distinct pattern warranting that terminology.”

If even a co-author was concerned, and the hospital’s pathology reports don’t support the diagnosis of colitis, the obvious question would be: how did the paper reach it’s conclusions?

The answer appears to be that the results underwent a second review. This second review is discussed in the Lancet paper, but there is no mention of the review changing the interpretation of the data,

Mr. Deer poses an important question:

[H]ow many peer reviewers would have felt comfortable approving the paper if they had known that the hospital pathology service reported biopsy specimens as largely normal, but they were then subjected to an unplanned second look and reinterpreted?

Which we are fortunate enough to have answered. Mr. Deer was able to obtain an answer from one of the peer reviewers:

“I’m surprised the GMC didn’t make more of this,” said David Candy, paediatric gastroenterologist at St Richard’s Hospital, Chichester, who reviewed the paper in 1997. “That’s an example of really naughty doing—to exclude the original pathology findings.”

“Really naughty doing”. Not very clinical but I think it tells the story well.

Is it possible that the hospital’s pathology service missed the condition? Apparently at least one author (Dr. Walker-Smith, a co-defendant with Dr. Wakefield in the GMC hearings) noted this in his GMC testimony:

And how bad was this “colitis,” such that the hospital’s pathology service didn’t spot it as the children came through? Walker-Smith told the GMC panel that he had “concerns” about the service and its ability to detect inflammation.

In his report, Mr. Deer counters with:

Yet inflammatory indices that were not reported in the Lancet paper, including serum C reactive protein concentrations and other blood tests, were almost all within normal ranges for the 12 children.6 And as an alternative explanation for any inflammation that was present, nearly all of the children had constipation with megarectum16 (unreported in the paper), which specialists say can cause cellular changes.

Mr. Deer attempted to speak with Dr. Dillhon, a co-author on the Lancet paper. Dr. Dillhon viewed the slides made from the samples taken from the children, and he graded them with Roman numerals to rank the degree of inflammation. At some point, those Roman numerals were translated into “non-specific colitis”.

So who translated these scores on the grading sheet into findings of “non-specific colitis” in the paper? Dhillon says it wasn’t him. He says he would like to see the slides again, but they are missing from the Royal Free laboratory. “He [Dhillon], Andrew Anthony, and Wakefield all looked at them,” I was told, on Dhillon’s behalf, by a senior member of staff at the Royal Free. “Andy [Wakefield] then synthesised their results into what appeared in the paper.”

But still, according to Mr. Deer, “…how the Roman numerical scores, histopathological gradings for a variety of sites in the colon, became the “colitis” findings might, under such circumstances, be anybody’s guess.”

Mr. Deer posits a possible scenario, based on Dr. Wakefield’s complaint to the press complaints commission:

Wakefield wrote: “When the biopsies were reviewed and scored by experts in bowel pathology—namely, Drs Dhillon and Anthony—these doctors determined that there was mild inflammation in the caecum, ascending colon, and rectum,” he said. “This was correctly reported as non-specific colitis in the Lancet.” In other words, it looks like it was Wakefield who translated the scores.

A companion editorial was published in the BMJ by Prof. Sir Nicholas Wright, warden, of Barts and the London School of Medicine and Dentistry, Queen Mary University of London. He lists in his conflict of interest statement: “He has provided expert opinion in the case of Wakefield v GMC and acted as a character witness for Professor John Walker-Smith.”

His editorial:

Does autistic enterocolitis exist?
Despite the retracted Wakefield study, questions remain

His conclusion:

Is autistic enterocolitis a histopathological entity or even an entity at all? In view of the lack of data and the entrenched position of many of the protagonists and antagonists, any firm conclusion would be inadvisable. The expert review, referenced by Deer, concludes that key areas such as the prevalence and best treatment of gastrointestinal disorders in people with autistic spectrum disorders are incompletely understood, and that evidence based recommendations are not yet available. We should remember, as recent experience in several fields has shown, that although science has its defects, it is a self correcting process. Time is, perhaps, the wisest counsellor of all. In the meantime, this case offers a salutary reminder for researchers and journal editors alike that coauthorship means bearing responsibility for what is written.

First, I would submit that Dr. Wright is not being clear on the subject. It is not whether autistics have a greater prevalence of GI issues, or whether there is a difference in the treatment for autistics. The question is whether there is a specific entity which is unique to autistics: autistic enterocolitis. Further, it is also a primary question whether “autistic enterocolitis” is causal in autism. While one can hide behind the “you can’t prove a negative” shield, the answers at present appear to be no to both questions.

Second, the idea that science is a self correcting process is often times true. In this case, it clearly is not. The science, the Lancet paper, was not corrected through science but through investigative journalism. Without the stories in The Sunday Times, Dr. Wakefield’s “science” would likely still be in the official record of The Lancet. Much more, the Lancet study and the presumed expertise of Dr. Wakefield would have likely been key in litigation in the UK and the US. Without Mr. Deer’s continued scrutiny, the facts behind the research into the Lancet paper, specifically that the pathology reports on those children were not consistent with the findings of the paper, would almost certainly not have come to light.

Returning to Mr. Deer’s article, he concludes:

So what should we make of all this? Now the Lancet paper is retracted, its findings don’t officially exist. And, if Dhillon is right in saying the slides can’t be found, the ultimate proof is missing. All we have are the pathology reports, which independent specialists seem to agree are largely unremarkable. “They wanted this bad,” commented Tom MacDonald, dean of research at Barts and the London School of Medicine and coauthor of Immunology and Diseases of the Gut. “If I was the referee and the routine pathologists reported that 8/11 were within normal limits, or had trivial changes, but this was then revised by other people to 11/12 having non-specific colitis, then I would just tell the editor to reject the paper.”

Clearly the Lancet paper should have been rejected. But this isn’t just a scientific paper that made a bad conclusion. This paper impacted multiple families inside the autism communities to believe that their child’s autism was caused by MMR. This paper led many families in the autism communities to apply poorly researched “therapies” to their disabled children. This paper led many families to stop vaccinating their children, leading to outbreaks of measles in the UK and elsewhere.

It is easy to go through Mr. Deer’s paper in the BMJ point by point in a clinical fashion, noting how the research went awry, showing that “autistic enterocolitis” has what appears to be no founding in science. But how does one express the reaction to so much damage caused by Dr. Wakefield’s investigation?

Of course, a further question I have and I bet I share with Dr. Wakefield’s supporters is this: is Brian Deer finished or is there even more yet to be unearthed in this sad tale of research gone awry?