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.
Left Brain Right Brain 
“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.”
That’s why they call it Housekeeping.
Challenge for Wakefield: Design a *blinded* medical test that demonstrates random (not self-selected for gastric issues) autistic kids have significantly more “enterocolitis” (however he wants to define it) than non-autistic kids matched for age and gender.
Walkiewicz say likewise that Fecal calprotectin is useful in predicting disease relapse in pediatric inflammatory bowel disease. Why would anyone still persist with claiming a need for biopsies when there is a good non-invasive measure available? Unless it is someone snatching at something, anything that would allow him to maintain the integrity of a discredited claim. It is sad that any researcher should reach such a pass but particularly one who has had such a powerful influence on some many people.
Nicely written. You’d think that a couple of hundred parents of kids who never got the “cure” Wakefield indicated that they’d be in line for, would be hopping angry that their child was put under general anesthesia and given a potentially dangerous procedure for NO reason.
The “diarrhea” that the original Wakefield 12 had was “overflow” diarrhea because the kids were backed up with feces. When they cleaned the kids out for the scoping the kids suddenly felt better and started acting more like themselves (and less sickly).
The proper controls for autistic kids if one is looking at “gut issues” are “mentally retarded.” Developmentally delayed kids are more likely to have this problem with constipation and overflow diarrhea. The constipation can cause the “nodular hyperplasia” because the feces stays put in the intestines for a longer time and the lymph system works harder to keep the bacteria in the feces from entering the blood, and so there are these nodules of lymph tissue.
And Wakefield is a low-life greedy scumbag, besides. He has tormented all these autistic kids put them on restrictive diets and his buddy Krigsman is putting autistic kids through this scoping now and prescribing very harsh drugs to treat apparently non-existent “inflammation” and the kids get put on restrictive diets with the idea that they have been getting high on gluten and casein, which is patently false.
If the kid has a reason to be a certain diet, that’s fine, but they shouldn’t have foods taken from them to make mummy and duddy feel like they are doing SOMETHING.
happy Valentine’s day Kev and Daughter!
Kev,
You’ve made a few misleading comments:
1) “They looked to see if any of the autistic kids had evidence of gastric issues over and above the average.”
This is not true. They only assessed the study and control groups for enterocolitis, a very specific GI issue. You’ll also note that any conclusion on the GI issues is very weak based on their own admission in the study:
“Gut symptoms were elicited but the children were too old for accurate reporting of retrospective gut symptoms confidently contemporaneous with MMR vaccination.”
That admission alone pretty much eliminates any chance of appropriately comparing this study to any other study on GI issues and Autism around the time of MMR vaccination.
2) “So, there’s not really any reason why blood cells wouldn’t be suitable to check for measles virus, despite Wakefield’s opinion.”
Even if I believe your anonymous doctor, his statement is not definitive. Since using PBMCs as a proxy for gut tissue in the study is a key assumption, it is incumbent on the the Authors to illustrate that this methodology is an effective substitute for gut tissue. Without this assumption, this study is unable to test it’s hypothesis.
You’ll note that they provide no credible scientific evidence or precident to support this. The study they reference was very small and only detected MV genome in a small percentage of patients, and it never actually did a test for efficacy.
They don’t list any studies to show that persistent MV infection would be detectable in the blood. This is quite telling. It is not difficult to find studies of MV that show it can remain undetectable in brain tissue for many years. Even the Omnibus trial defendent’s witness (measles expert) discussed these conditions.
The other key assumption which receives no discussion or support in the Baird study, is that a persistent measles infection triggered by MMR causing damage would still be detectable 10 years later. Again, no discussion, no references to support this.
Given that they don’t support their assumptions with evidence, it pretty much means their methods are unable to appropriately test their own hypothesis.
Given that this study was clearly intended to be compared to Wakefield’s results, I’m surprised that it was specifically designed to prevent a scientific comparison.
The only interesting data point I take from the study is that 23 of the 98 Autism cases were of the regressive type. That’s a higher percentage that I have heard in the past.
Schwarz,
_”This is not true. They only assessed the study and control groups for enterocolitis, a very specific GI issue.”_
So entercolitis is, we agree, a gastric issue. Therefore they did, as I said, test for gastric issues. Therefore what I said was true, if not tightly defined.
_”That admission alone pretty much eliminates any chance of appropriately comparing this study to any other study on GI issues and Autism around the time of MMR vaccination.”_
Not really. It might call into question their ability to draw firm conclusions about the gastric issues side of the study, but it most certainly does not invalidate the study.
_”Since using PBMCs as a proxy for gut tissue in the study is a key assumption, it is incumbent on the the Authors to illustrate that this methodology is an effective substitute for gut tissue”_
Not so. It is incumbent upon Wakefield et al to establish that:
a) Their original hypothesis is scientifically valid
b) Scoping is the only way to establish their presence of MV and MV related ‘damage’ to the gut
until they do, any approach that can accurately find MV in the body is valid.
_”Without this assumption, this study is unable to test it’s hypothesis”_
The purpose of this study was:
_”To test the hypothesis that measles
vaccination was involved in the pathogenesis of autism
spectrum disorders (ASD) as evidenced by signs of a
persistent measles infection or abnormally persistent
immune response shown by circulating measles virus or
raised antibody titres in children with ASD who had been
vaccinated against measles, mumps and rubella (MMR)
compared with controls.”_
which they did admirably.
You seem to be falling into the same trap as John Stone and Wakefield himself – assuming that their data, methods and results are valid (which they have been shown not to be) and then being puzzled when no one else can match them.
Whats your opinion on why Wakefield et al wouldn’t share their samples with the Afzal team by the way?
“Since using PBMCs as a proxy for gut tissue in the study is a key assumption, it is incumbent on the the Authors to illustrate that this methodology is an effective substitute for gut tissue”
——————————————
PBMC has been used as a proxy for other gut infections see example of rotovirus, cholera.
But here’s the deal, is PBMC only considered to be an effective substitute if it gives you a desired result?
This paper seems to have used PBMC as a proxy:
Kawashima H, Mori T, Kashiwagi Y, Takekuma, K, Hoshika, A, WAKEFIELD, A. (2000). Detection and sequencing of measles virus from peripheral mononuclear cells from patients with inflammatory bowel disease and autism. Dig Dis Sci 2000;45:723–9.
So if PBMC is unsuitable, then presumably Dr. Wakefield would have known that as a co-author, and if it is suitable as seems to be indicated by the use of Kawashima, et. al. (although others have shown discrepancies and potential contaminations in the PCR analysis), then Baird, et. al. were correct in choosing this as a proxy.
As for the rather high percentage of children with autistic enterocolitis seen by Dr. Wakefield, would it be reasonable to consider that one explanation might be selection bias; since children who don’t exhibit gut problems are not usually referred for gut problems?
Kev,
[i]”So entercolitis is, we agree, a gastric issue. Therefore they did, as I said, test for gastric issues. Therefore what I said was true, if not tightly defined.”[/i]
So a gastric issue (enterocolitis), we agree, is not the same as Gastric Issues as you stated. Therefore what you said was misleading and not accurate as I stated above.
[i]”Not really. It might call into question their ability to draw firm conclusions about the gastric issues side of the study, but it most certainly does not invalidate the study.”[/i]
If you read my post carefully I didn’t state it would invalidate the whole study, but any attempt to compare it with a study that looked at GI issues and Autism was impossible. That statement is still correct.
[i]Not so. It is incumbent upon Wakefield et al to establish that:
a) Their original hypothesis is scientifically valid
b) Scoping is the only way to establish their presence of MV and MV related ‘damage’ to the gut
until they do, any approach that can accurately find MV in the body is valid.[/i]
Baird et al put forth a hypothesis. They need to show that their methods could properly test the hypothesis. If they can’t demontrate that measuring PBMCs is an effective proxy for gut cells, they can’t properly test their hypothesis. It’s pretty simple and THEIR study has nothing to do with Wakefield’s methods UNLESS they are trying to compare their work to his.
Obviously they weren’t trying to compare their work to his, because they specifically designed the study to make such a comparison unscientific.
The flawed methodology, has nothing to do with Wakefield.
Let’s boil down their hypothesis:
1) To determine if the event of MMR vaccination resulted in a pathogenesis of autism
2) To determine this by testing 12 year old children for remaining signs of MMR genome and titers
3) To detect signs of MMR genome by testing the blood and PBMCs
Let’s look at the assumptions here:
In order to test #1, #2 and #3 must be true.
A1: MMR vaccination results in a pathogenesis of Autism. (this is the core of the hypothesis)
A2: IF MMR vaccination resulted in a pathogenesis of autism, then signs of MV genome would be detectable 10 years later
A3: If the MV genome was detectable after 10 years then it would be detectable in the blood or PBMC
Since the study resulted in a null hypothesis, ONE of the assumptions must be false.
That means one or more of the following was true:
C1) MMR did not result in a pathogenesis of Autism
C1a) The pathogenesis of Autism does not result in MMR genone in the body
C2) The MMR remnants in the body did not remain for 10 years after the original vaccination and subsequent injury
C3) The MMR remnant still in the body can’t be detected in the blood or PBMCs
The study methodology was not designed to independently test for C2 and C3, nor did the Authors provide credible evidence for to show that the A2, and A3 assumptions were credible, they are unable to independently test for their hypothesis — A1.
This means they can’t reach a conclusion on their hypothesis.
The method of Wakefield et al, are completely irrelevant when evaluating this study. It appears to me that you are getting distracted with issues in the Wakefield study, and that you are missing some fundamental flaws in this one.
Regan,
The Wakefield study used PBMCs to detect MV in a study group of 9 children SUFFERING GI ISSUES who were younger and therefore much closer in age to the original diagnosis. They only detected MV Genome in 33% of the study group, but they couldn’t have fully validated it as a proxy without actually testing the gut tissue to determine if MV was present in Gut tissue of the same 3 children.
Additionally, their study was a case study, not an epidemiological one. In a case study where they were trying to detect MV genome, any postive results was sufficient (i.e. even if the PBMCs were 5% effective, you could still get a positive result).
The Baird study is trying to conclude that there was no MV genome present in the gut. That would require validation of the method as a proxy for testing gut tissue, otherwise they would be unable to make a NEGATIVE conclusion.
Baird et al, are cherry picking the methodolgy, while using it on a completely different study group profile — no GI issues, much older children.
Baird et al, are claiming no association, so they have to show that the PBMC method is actually a 100% effective proxy which means someone must have tested both PBMC and the gut tissue FIRST to determine if the method is effective.
The authors give this topic very little discussion and no comparable evidence that this approach is valid.
_”So a gastric issue (enterocolitis), we agree, is not the same as Gastric Issues as you stated. Therefore what you said was misleading and not accurate as I stated above.”_
You said ‘not true’ – it _is_ true. Whats hard to get here?
_any attempt to compare it with a study that looked at GI issues and Autism was impossible. That statement is still correct._
No, its wrong. The GI issues part of the paper was not ever in the hypothesis of this paper. It was reported as a side effect. It doesn’t detract from anything.
Once again you’re falling into the trap of assigning significance to the gut cells. PBMC’s don’t have to be a proxy of anything. They just need to be able to be shown to be a good source of data for MV.
Here’s the relevent section from the Abstract of the paper Baird et al quote:
That seems fairly clear to me. Unless you (or Wakefield) has any _science_ to undermine it, it seems that PBMC’s are reliable sources of data regarding historical MV.
Wakefield’s entire project was rooted in claims that MV could be found in the PBMC’s of autistic children. This was the pivotal issue upon which the UK lawsuit collapsed. When results for autistic and control groups (including his own children) were unblinded, they were the same.
Of course, this research has never been published.
Kev,
Need I spell out that there is a big difference between an Issue (singular as you stated yourself multiple times) and issues (plural, which you wrote in your article). They tested for a single disease, not multiple as you implied.
Your original article is written to imply they detected for a range of GI issues, they did not. Your original article implies that the results can be compared to Wakefield’s. They can not since the issue (SINGULAR) they identified was different from Wakefields.
I never stated that the GI issues were part of the hypothesis. My statement is that the lack of credible evidence around the GI investigation in Baird et al., renders any comparison with Wakefield’s study unscientific. You need to read my posts more carefully, or point out where I stated that this particular problem invalidates the study or hypothesis.
WRT to the PBMCs. Where in that excerpt is the evidence to show that PBMC’s are an appropriate proxy for Gut Tissue?
We already had evidence that MV genome could be detected in PBMC’s (from their reference). What neither studies provide, is evidence that when there is MV in gut tissue, that you will always find it in PBMCs.
They did not validate that it is an effective proxy for Gut tissue at all. If I missed it, please point out the evidence. That is another reason the results can’t be compared to Wakefield (although the first reason is good enough).
“That seems fairly clear to me. Unless you (or Wakefield) has any science to undermine it, it seems that PBMC’s are reliable sources of data regarding historical MV.”
How do you manage to interpret those results to say that PBMC’s are a realiable source of data regarding historical MV?
All that the data tells you is that PMBCs sometimes have traces of MV after exposure. We ALREADY KNEW THIS. They can’t provide you a reliability statistic, nor can they provide you with a variability statistic. In order to validate a methodology both of these factors would need to be known.
You forget, this study was not designed to test the effectiveness of PBMCs as a proxy, it ASSUMED that it was a proxy and based on that assumption is testing a different hypothesis.
You can’t test the effectiveness of a measurement method in a study designed such that it is ASSUMED the method is effective beforehand. It would require a different design. i.e. knowing exactly what type of measles infection each participant had and then seeing if the measurement method was accurate. Clearly this is impossible here since they were using this measurement method to determine the type and rate of measles infection in the study group.
At best, the study design might be able to determine if blood results might correlate to PBMC MV results, but again, that does not address enough assumptions help test their hypothesis, since it doesn’t address either method’s efficacy in determining whether persistent measles infection caused historical injury after vaccination.
Again, you’re over-complicating a simple issue. Can PBMC results indicate the presence of historical MV? Yes, according to this paper and the paper this paper uses to support its opinion, they can.
This:
_”WRT to the PBMCs. Where in that excerpt is the evidence to show that PBMC’s are an appropriate proxy for Gut Tissue?”_
is a meaningless point. They don’t have to be a proxy. They just need to be able to give accurate data about MV. The available science indicates that they do. Unless you have any other science that refutes this then I don’t know what to say – you’ll just have to ignore it I guess.
I’m still interested in your opinion as to why you think Wakefield et al refused to participate in, or hand samples over to, the Afzal team. I realise you can’t _know_ but I would like your opinion.
Given that, if measles virus persists in the germinal centres of lymph glands, and lymph glands are chock full of, well, lymphocytes, and lymphocytes are PBMCs… then I’m struggling here… even before I get to trying to understand how, if the virus is also in CSF, and CSF contains PBMCs… how it can be that the PBMCs wouldn’t test positive by RT-PCR if measles was replicating in either the gut or the brain.
Uhmmm…. Aha! I’ve got it! The virus USED to be there, but succumbed to clearance just before anybody looked.
Now you see me, now you don’t…
I love these people.
I was watching a show on the Loch Ness Monster earlier today. The folks who cling to the idea that their is some sort of marine reptile living in the depths of the loch, and I’m not disputing that it’s a possibility, have postulated that he hides in caves whenever sonar is deployed. So it’s still possible that there is an animal but it/they can’t be detected if they don’t look in every nook and cranny. Can’t argue with that, can we?
So let’s review; Wakefield is the only one who says he found measles and no other lab can find it. Why? They aren’t looking in the right place.
Here’s the thing, Wakefield is the only one required to produce evidence of the virus because he is the sole source of the reports that it exists. Everyone else is forced to look for it using the only means available because so many people won’t let it go.
As long as there is the slightest chance it is there, we can’t prove it isn’t. Is that about right?
Kev,
Taken from page 3 of the study:
“We used PBMC in this study as proxy for
gut mucosal cells which were not obtained for ethical reasons.”
The study authors were clearly using it as a proxy.
If you don’t know the efficacy of a detection method, you can’t use it to show a negative correlation. You can certainly use an untested measurement technique to show a positive correlation IF you get a results. Can’t you see the difference?
If you don’t know whether it’s an appropriate proxy, then a negative result tells you nothing. But a positive result certainly tells you there was MV presence.
My guesses as to why he wouldn’t turn over the samples are (in no particular order):
1) He knows he had incorrect results
2) He doesn’t trust the other group to do the proper tests, or maybe doesn’t trust them to publish regardless of the outcome
3) Given the amount of legal activity around this whole thing, his lawyers advised him not to turn over anything.
Any of these reasons appear plausible to me without knowing any other facts.
Brian, when you can provide evidence that PBMCs are an effective proxy for gut tissue, I’ll believe you. This is about evidence right?
Notmercury,
I think you must have missed the discussion. We’re discussing the Baird et al study, not the Wakefield one.
Baird et al are perfectly welcome to design any type of study they want. Unfortunately, people here are comparing the results to Wakefield, when the study design specifically precludes a scientific comparison.
The other unfortunate thing is that the Baird et al study uses detection methods without any references as to their efficacy in testing this hypothesis. They also do tests 10 years after the injury occurred.
As I said earlier, the one interesting piece of information I see from this study is that ~25% of the Children studied had regressed.
Oh well, please pardon the intrusion. I didn’t realize that the boundaries of the discussion had been posted.
As much as it seems you would like to isolate this study in order to label it fatally flawed and dismiss it entirely, I’m afraid I can’t agree. This study doesn’t stand in isolation any more than Wakefield’s several studies. It adds to the body of knowledge and evidence that Wakefield’s claims cannot be replicated or confirmed.
I understand that the study has it’s limitations and you’ve made it clear that it doesn’t test these hypotheses to your satisfaction but the design and methods were sound.
Wakefield found measles in PBMC using PCR methods that were prone to false positive results. The same assays that were used to detect MV in gut mucosa. If there are any assumptions to be drawn from that, it would be that his results for gut tissue were also false positive.
You said: “They also do tests 10 years after the injury occurred.”
So each and all of the study participants received the MMR ten years prior to this study? That doesn’t sound right to me, could you check on that for me?
“As I said earlier, the one interesting piece of information I see from this study is that ~25% of the Children studied had regressed.”
That is interesting but a unique finding. It does indicate an homogenous population and representative cross-section were used. In other words, it wouldn’t appear any subtypes were eliminated along the way.
they wiley interscience link isn’t working. says I need to accept cookies. What’s the citation? I can find the journal myself…
nevermind, I copied the link, instead of clicking on it and removed ABSTRACT?CRETRY=1&SRETRY=0 and it worked.
Sorry. Meant to say *not* unique above.
Not Mercury,
I agree that all studies add to the body of knowledge. However, justifying the methods based on another studies’ poor methods is not a logical argument.
If you feel that the methods of this study were sound, then please produce the evidence that PBMC’s are an effective (i.e. no false negatives) proxy for gut tissue — the study discussion and references certainly didn’t.
Or maybe you could provide evidence that a previous bout of persistent measles infection is detectable in the blood 10 years later — the study discussion and references certainly didn’t.
Both of these scientific assumptions are critical to test the hypothesis.
If you read the study (did you read the study?), you’ll note that the average age of the study and control groups was ~12 years old (11.6, SD=.88). Given that MMR is typically applied around 2 years of age (before actually), that leaves about 10 years in between. Since the study population was a cohort born in 1990-1991, that makes the age pretty homogenous as noted by the SD.
Regarding the regression statistic, it was a lot higher than I had heard in the past.
I’m not that concerned about false negatives, I wouldn’t mind if the effective detection rate was under 10%. It still wouldn’t and couldn’t explain why this study, and two others, were unable to detect a single example of persistent measles infection in large populations of autistic children. Many more than Andy had access to, by the way.
It isn’t a slam dunk, no, not as long as we have to consider the possibility that measles can persist in some places and not show up in peripheral blood cells.
I deal in probabilities, not slim possibilities.
average age 12, right, but age distribution included children that were much younger and received the MMR more recently. What was the average age of the children in Wakefield’s studies and were there any children that were still measles positive (according to AW) after 10 years?
Wakefield has claimed that these kids are chronically infected, not that the infection clears up given enough time.
He made similar claims for Crohn’s patients and held up PCR data as evidence there as well. Since other researchers had access to gut biopsy material from those patients, Wakefield was forced to capitulate.
Together, the history and attempts to replicate, not disprove, Wakefield’s claims, add up to an extremely unlikely chance that autism has anything to do with persistent measles in the gut while negative in PBMC.
Regarding regression, it depends on how regression is defined. If the stat was higher here it might be a matter of selection bias that the authors discussed, since parents were made aware that this was to be an MMR study. It certainly wouldn’t indicate those made autistic by the MMR were cleverly excluded.
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1728330&blobtype=pdf
Although all attempts to detect measles virus genome in
Crohn’s affected tissue using RT-PCR have failed, a recent
study based on a Japanese-Royal Free Hospital group collaboration
have claimed detection of the presence of wildtype
and vaccine-type measles virus genome in peripheral
blood mononuclear cells from IBD patients (as well as
patients with autism).37 However, the NIBSC study also
attempted to detect measles virus genome in lymphocyte
preparations from IBD and control patients with paired
tissue specimens and all lymphocyte preparations were
negative. The experience with clinical specimens at NIBSC
has shown that even with the most meticulous technique,
cross contamination of specimens can occasionally occur.20
PCR contamination has also been reported by the Royal
Free Hospital group.35 A range of methods and considerable
experience is needed to recognise non-specific
reactions which might be misinterpreted as positive if confirmatory
techniques are not applied.
Notmercury,
The problem isn’t that you’re dealing with low detection rates, you’re dealing with unknown detection rates.
If you want to prove a negative, you have to know the rate of false negatives.
You also have a string of assumptions here (age of the participants, unknown GI issue status) each of these with unknown probabilities. Since it is a string of assumptions, the probabilities must be multiplied. That usually makes an extremely low probability in the end which would match the result we saw — obviously, there could be any number of other reasons for the null result, including a lack of correlation.
“average age 12, right, but age distribution included children that were much younger and received the MMR more recently. What was the average age of the children in Wakefield’s studies and were there any children that were still measles positive (according to AW) after 10 years?”
I’m not sure where you got the younger group from? The study group was taken from a cohort born in 1990, 1991. This is corroborrated by the Standard deviation of 95% of the study group was
Notmercury,
Sorry about that last post. Those greater than less than signs always get me.
…
I’m not sure where you got the younger group from? The study group was taken from a cohort born in 1990, 1991. This is corroborrated by the Standard deviation of less than 1. If I remember my stats, that means that greater than 95% of the study group was within 2 years of the mean and 99.7% within 3 years of the mean. Of course, very few details were published in this study making it hard to make any judgements on anything.
The children in the Wakefield study (2000) had a median age of 7 years; range, 3–14. His original study ages were: (4, 9.5, 7, 10, 8, 5, 3, 3.5, 6, 4, 6, 7). All of the study group in the Uhlmann study had ileocolonic lymphonodular hyperplasia.
You stated: “Wakefield has claimed that these kids are chronically infected, not that the infection clears up given enough time.”
Yes, and they studied children with active GI issues. Additionally, they made no definitive claims at all. From their own words, it just raises questions:
“These preliminary studies have focused principally on MV. We have not excluded the presence of alternative infections. Viruses may persist elsewhere, or exert a transient effect not requiring subsequent persistence.
…
Our study raises many questions—most importantly, does MV play an aetiological role in intestinal inflammation in developmental disorder? The study reports for the first time an association between MV infection and ileocolonic lymphonodular hyperplasia and ileocolitis in children with developmental disorder.”
As for PCR, I’ve heard and read so many potential issues and limitations regarding the technique I don’t know what to believe anymore. Don’t mistake my issues with the current study as support for the PCR results of AW’s study (2000), for I am skeptical of those results.
However, that issue does not change the issues with this current study, nor with the invalid attempts to compare the results.
Sigh… Two more corrections to the above. The two references to Wakefields study (2000) should read Uhlmann’s study (2002)
“If you want to prove a negative, you have to know the rate of false negatives.”
I can’t offer any insights concerning the authors’ intentions, but who said anything about proving a negative? The way I read it, they looked for measles and measles antibodies and found no differences between ASD and controls. Failed to replicate or confirm.
Well, they actually did replicate Wakefield because he didn’t really find any MV either.
That’s why this whole MMR fiasco is a ridiculously moot issue. Wakefield never found MV in the gut…end of argument.
Just ask Bustin.
NotMercury,
If you read their conclusions carefully, they are worded as though they proved the null hypothesis. That would be proving a negative.
“There is no difference between ASD cases and controls in circulating measles
genome or measles antibody levels.”
You can’t make that statement without knowing the rate of false negatives or knowing the efficacy of using PBMCs as a proxy for lingering MV genome.
You’ll note there is no comment on replication of other studies, and I’ve clearly pointed out due to numerous issues (including fundamentally different study groups) in scientifically comparing this study will Uhlmann.
I started to tic through the comments, but one possibility is rather than focus on possible false negatives, perhaps the case is the susceptibility of some studies to false positives.
This paper seemed to discuss what and how those might be, and provide another point of comparison:
D’Souza, Y., Fombonne, E., and Ward, B.J. (2006). No Evidence of Persisting Measles Virus in Peripheral Blood Mononuclear Cells From Children With Autism Spectrum Disorder. Pediatrics. Vol. 118 No. 4. pp.1664-1675.
http://pediatrics.aappublications.org/cgi/content/full/118/4/1664
“There is no difference between ASD cases and controls in circulating measles
genome or measles antibody levels.”
That is an entirely accurate and reasonable statement, as far as I can tell. Key words being circulating and antibody levels. No differences. How is that misleading?
NotMercury,
Good catch, I misread that one. They only draw conclusion based on the results of finding MV genome in the blood. They draw no conclusions on the results of the PMBC PCR results at all.
Unless someone is claiming that looking for MV in the blood is a proxy for gut tissue, then it is crystal clear that this study can’t be compared to Uhlmann. It still leaves them with a flawed hypothesis as well.
Those promiscuous circulating monocytes. Puttin’ the ‘P’ in PBMC.
Crystal Clear? If you say so.