Crumbling science

3 Oct

Krigsman, Wakefield Error Highlighted

A study this month in Paediatrics tackles head-on the ‘science’ that is still yet to be published (a number of years later) by Arthur Krigsman in which he claims that he has found evidence of persistent measles virus in autistic kids and thus backing up the work of his business partner Andrew Wakefield.

In layman’s terms what this study did was replicate the result of Krigsman et al and then eliminate the poor science that led Krigsman to his erroneous conclusions. Of the samples that still showed as positive, no trace of MV was found.

The real-time assays based on previously published primers gave rise to a large number of positive reactions in both autism spectrum disorder and control samples. Almost all of the positive reactions in these assays were eliminated by evaluation of melting curves and amplicon band size. The amplicons for the remaining positive reactions were cloned and sequenced. No sample from either autism spectrum disorder or control groups was found to contain nucleic acids from any measles virus gene. In the nested polymerase chain reaction and inhouse assays, none of the samples yielded positive results. Furthermore, there was no difference in anti-measles antibody titers between the autism and control groups

Now thats pretty hardcore science language. I’ve emailed the authors to see if they are willing to explain (and be quoted) on an English translation of the above but in essence, the facts are as I state them above. Krigsman et al (and Wakefield before him?) failed to eliminate false positives and counted them as part of his result set. When these false positives are eliminated then the samples left contain no MV.

I’m hoping that Bart Cubbins, No Mercury, Maria, Ms Clarke et al (who are wise in the ways of this terminology) might offer more input into the meaning of the exact phraseology used and as I say, I’ve mailed the authors for clarification too. In the meantime – Krigsman’s (unpublished) work is now pretty much refuted (by published work).

Daubert’s Revenge – Martha Herbert

As reported by Autism Diva, Dr Martha Herbert has now reached the dizzy heights Boyd Haley and Mark Geier have scaled in having her ‘expert testimony’ found severely wanting following a Daubert hearing.

Herbert basically claimed that a childs autism (diagnosed by her following a differential diagnosis) was caused by mold. Yes, mold. However, upon being cross-examined:

When asked whether there is ‘any evidence that mold is a trigger [for autism],’ Dr. Herbert responded by referring to research regarding brain inflammation and immunological abnormalities in autism. Asked about research showing that ‘any of the mold or any of the mildew or any of those other things also cause brain inflammation,’ she responded ‘that’s a hole in my knowledge. In terms of autism, I don’t believe that’s been done.’

Right. Well, thank goodness she’s so rigorous. Wouldn’t want to just make assumptions right? That would just be a waste of everyone’s time right?

In another classic piece of thinking Herbert goes on to say:

Dr. Herbert commented, ‘she doesn’t have any of the known genetic syndromes, or known in-utero infections. I personally consider it symptomatic, but not in the established set of categories, in that I hope that when more research is done she’ll move in the symptomatic category.’

In other words she doesn’t know what caused the childs autism (gasp!) but that it doesn’t fit any known profile but that maybe some research at some unspecified point in the future might help categorise it (whatever ‘it’ is).

Oh, it gets better.

Dr. Herbert was asked, ‘[c]an you say to a reasonable degree of medical certainty that if Emilia Ward had been in a sterile environment, she would not suffer from autism” She responded, ‘My guess would be, yes, that she probably would not.’ The basis for that ‘guess,’ she testified, was ‘her having regressed after the mold exposure and that she gets worse with exposures.’

Wait… _guess_ – her _guess_ ? Well surely she meant ‘informed opinion’, or ‘scientific judgement based on the evidence to hand’…..except there _is_no evidence to hand:

In response to questions she acknowledged that she has never done any research on mold or mildew as an environmental toxin, and is not aware of any published peer review articles that link mold and mildew exposure to autism.

And so it is no great shock to find the court saying:

Dr. Herbert’s publications indicate that she is an outspoken advocate of increased attention to the possibility of environmental influences. Even she, however, despite that acknowledged perspective, speaks in her published work of possibilities and potentialities, rather than of the ‘reasonable degree of medical certainty’ to which she offers to testify under oath in this case.10 Neither Dr. Herbert’s publications, nor any others cited, identify mold exposure as even a suspected, still less a known or proven, trigger of autism……Dr. Herbert’s method, to the extent the Court can discern it from the materials offered, is a series of deductions based on possibilities…..*Clearly, Dr. Herbert’s method is not generally accepted in the scientific community*. Dr. Herbert’s theory of environmental triggers of autism may some day prove true. It has not yet. *Her proffered testimony does not meet the standard of reliability required by the case law*, and cannot be admitted in evidence at trial.

FDA Spanks Mercury Milita

Back in 2004, Dr Paul King of dr-king.com, uh, fame, submitted a ‘citizen petition’ to the FDA requesting:

[The FDA]…take numerous actions pertaining to vaccines and other FDA-regulated products containing thimerosal or other mercury-based preservatives….After review and consideration, we deny the petition for the reasons stated below in this response.

The response is very detailed (the whole thing is available at Kathleen’s site) but can be summed up in one quote:

The evidence on which your petition relies either does not support your requests, or is too flawed to be considered valid scientific evidence.

Which seems to be something of a growing refrain for the mercury (and apparently mold!) militia.

Damn science with its rigorous pursuit of accuracy eh? If only we could rely on opinions and guesses.

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34 Responses to “Crumbling science”

  1. Bartholomew Cubbins October 3, 2006 at 14:19 #

    It’s not easy to do great science. But it is easy to do good science.

    Whether the root be laziness, incompetence, or dishonesty, I think the important thing is that it is now abundantly clear that the QPCR-based claims by some, of vaccine-induced Mviral prevalence and its relationship to autism, are completely wrong.

  2. ameliorator October 3, 2006 at 14:21 #

    Snarkalicious!
    I have really got to read “When Prophecy Fails” – about when doomsday cults reach and pass the date they said the world would end, and why this tends to strengthen their belief rather than dissuade them from it. There’s a psychological phenomenon that I think must be applicable to the autism-mercury warriors.

  3. clone3g October 3, 2006 at 15:20 #

    The obvious flaw in this research is the lack of biopsy samples from the guts of autistic children. I believe David H. and others have pointed this out before.

    Of course it’s possible that the virus is hiding out only in the guts of autistic children but one is left to wonder how measles was detected in PBMCs from autistic children using the same, apparently flawed, assays employed by Wakefield et al.

  4. LB October 3, 2006 at 16:30 #

    IF toxic mold is so wonderful why are there little men in suits (complete with breathing apparatus) who come in an try and remove it? So, her arguement was not a very good one if she just said it was her guess when there is evidence that exposure to mold effects the body. So there are alot of things that aren’t mentioned – like what kind of mold and did other family members suffer health concerns. I have seen some people laughing off the idea that mold could do anything at all – but I think it is fairly accepted that like mercury poisoning it is not a good thing. What needs to be sorted out is if it affects autism – not whether this stuff is good or not.

  5. everglade October 3, 2006 at 19:51 #

    LB: People who clean up mold wear personal protective equipment because inhaling a lot of it can be irritating. If you’re not allergic to mold and don’t have one of a few specific respiratory conditions that are easily aggravated, having it in your house isn’t going to hurt you.

    Mold spores are all around us, all the time. Even if you could somehow remove every spore from your house, you’d be in contact with them the second you walked outside. Remediating house mold is a good idea, not because of health risks, but because of the likelihood that whatever water source is allowing the mold to grow is also doing structural damage to the house.

  6. Ms. Clark October 3, 2006 at 20:43 #

    The point of Dr. Herbert’s testimony is that you can take a developmentally normal kid, expose her to some unspecified mold or mildew and make the kid autistic. HOW??? Dr. Herbert doesn’t know, she just is pretty sure it’s possible, and then there’s the whole vanilla air freshener incident… Dr. Herbert is taking questions, apparently over on the AWARES conference site. She might be able to clarify if she has filled any of the “holes” in her knowledge about mold and autism since her testimony.

    Is there any reason to think a virus could be present only in the walls of the intestine and simultaneously be totally absent from the blood of a child? Any research that shows that? D’Souza “found measles virus” in the blood of both ASD and NT kids, but then found that there wasn’t really any measles in either group by completing the testing correctly (that’s the remelt curve and cloning and sequencing of the amplicons, as I understand it).

    I see the mercury (mold?) militia as the lone hold-outs from WWII dutifully on duty on South Pacific islands, the Japanese soldiers who continued to “fight” long after the war was over… Bonzai! :-) No racism intended.

    You might be able to ask Dr. Ashwood questions about the Wakefield non-findings on the AWARES conference board, too. His review paper cites some Wakefield papers.

  7. LB October 3, 2006 at 20:56 #

    It all depends on the type of mold, concentration and exposure. Unless the person has a surpressed immune system or are particularly allergic (which if that was the case the doctor could have tested for that) however – there is a particular mold toxin that can effect all kinds of people. Mold in and of itself can be used for cheese and things like that and is very common – penicillan is a type of mold too isn’t it (or maybe I am thinking of something else). There are supposedly thousands of different types so if this woman was a scientist she really needed to do some specifying here and not say “mold”. I am not saying I agree with her – but that the argument itself isn’t productive without using any specific facts. My mother is highly allergic to mold and still gets a rash where she was tested for it if she is exposed to it. So it seems like there are things that could have been presented to support this woman’s theory if it was the case.

  8. María Luján October 3, 2006 at 21:09 #

    Hi, Kevin
    First, thank you for your citation of me.
    I have just requested this manuscript to the author.
    After my analysis, I will post then, if you are interested, my questions/ideas/discussion about it
    María Luján

  9. Ruth October 3, 2006 at 21:32 #

    LB-

    Autism affects how the brain develops before birth. Allergies or toxic exposure of many kinds in a child 2 or 3 years old has not yet been demonstrated to result in autism. Kids in Japan, Iraq and Romania who were exposed to toxic alkyl mercury developed peripheral nerve damage, constricted vision and other symptoms, but not autism.

    Mold toxins can be quite deadly. In many parts of Asia, aflatoxin from mold in food causes most of the liver cancer.

  10. anonimouse October 3, 2006 at 22:50 #

    Mold doesn’t cause autism. Neither do vaccines.

    I think the FDA’s response to the King petition is interesting, because it really lays a big fat comprehensive smackdown on the pathetic science these trolls keep rolling out with. If I were a betting man, I think in a few months we’ll be seeing a similar governmental response regarding another mercury loon initiative.

  11. Joseph October 4, 2006 at 03:16 #

    It’s clear that the mercury militia is increasingly becoming the toxic militia. The thimerosal hypothesis for the autism epidemic is no longer plausible and they know it, so their new party line is that “it’s not just the mercury”. They are moving on three different fronts at this point: (1) Other vaccine ingredients, (2) environmental pollution, and (3) misc. toxic compounds. At least there are researchers out there who don’t waste their time and do look into real causative factors.

  12. Ms. Clark October 4, 2006 at 08:53 #

    I agree Joseph, I don’t think they’ll find anything to (common) toxic exposures being a cause of autism, but Dr. Hertz-Picciotto’s CHARGE study is looking at lots of different chemical exposures to see if there is something that seems to correlate with autism dx’s. So far she’s found nothing when looking for mercury in ASD kids. She said at one point that flame retardants were more likely than mercury. I’ve heard Dr. Rodier say that pesticides were a good place to look. Look at all the time the mercury fanatics have tied up in demanding that people prove what they believe is true, when they could have been chasing after something more likely. Even though I don’t think they’ll find it, it would be more productive to cut back on pesticide and flame retardant exposure, seems to me, rather than constantly hammering the vast conspiracy to destroy the world through vaccines (and the variations on that theme) that the Hg parents keep chanting, fingers stuck in their ears and all.

    The thing is, if the “epidemic” has occurred more or less simultaneously, worldwide, then it logically would seem to be something that is of more or less equal prevalence worldwide and that has increased at a more or less equal rate worldwide… I have a hard time believing that there is such a thing, unless it would be carbon dioxide or something like that. Indians and Chinese have been dosing themselves on OTC mercury and lead containing medicines for eons, so I think we can rule out thimerosal as a hypothetical sudden cause of a hypothetical autism increase…

  13. bonni October 4, 2006 at 08:55 #

    When Prophecy Fails

  14. ameliorator October 4, 2006 at 13:01 #

    Bonni – Thanks for the link! I think the 5 conditions are clearly met here.
    Don’t know about the political examples they cited, though…I think they’re getting away from the kind of phenomena the book was about.

  15. anonimouse October 4, 2006 at 17:09 #

    As I’ve said before – mercury woo is dogma. Try to convince someone that their God of choice doesn’t exist, for example, and all they will do is become more entrenched and dogmatic in their position.

  16. Not Mercury October 5, 2006 at 00:52 #

    Here’s a question: Why didn’t Wakefield report false positives in his controls?

  17. David N. Andrews MEd (Dec 2006) October 5, 2006 at 01:55 #

    NM: “Here’s a question: Why didn’t Wakefield report false positives in his controls?”

    Um… because he wanted them to be real ones….?

  18. MAría Luján October 5, 2006 at 06:06 #

    Honestly, I do think that the overall issue is far far more complicated that simply a discussion of beliefs-dogma vs reason-science ( even when sometimes some vocal proponents/detractors reach this level).

    1-
    “A philosophical analysis of the evidence-based medicine debate”:http://www.biomedcentral.com/1472-6963/3/14#B37

    2-
    “Seven characteristics of medical evidence”:http://www.blackwell-synergy.com/doi/abs/10.1046/j.1365-2753.2000.00244.x

  19. Ms. Clark October 5, 2006 at 07:34 #

    It’s possible that Wakefield found “measles” in all of his control subjects but tossed out that data because it wouldn’t make him any fortune or fame, like finding it just in ASD kids would. If more labs will test samples from non-ASD people using the useless primers Wakefield used, and they find “measles” all over the place, and then they sequence the DNA and prove that there’s no measles there at all… then they can show that there never was any measles in Wakefield’s kids’ guts, because everyone will know that the primers didn’t signal measles at all, they signaled the finding of some human DNA, in a human (gasp). Until then Wakers can, and probably will, continue to claim we are all just picking on him as will his acolytes.

  20. David N. Andrews MEd (Dec 2006) October 5, 2006 at 14:00 #

    Should be remembered also that the original ‘regressive thing’ he was looking at as being possibly linked to the MMR vaccine was not actually autism, per se: it was Heller’s syndrome – which is a highly different issue.

    The project was hijacked and autism seemed, I suppose, to be a much more ‘catchy’ thing to link it all to. Brian Deer’s site has two copies of the initial documents, and the switch is evident in those documents.

  21. Catherina October 5, 2006 at 14:24 #

    Translation of the PCR snippet in the first section (read http://en.wikipedia.org/wiki/Polymerase_chain_reaction for background)

    The method uses 2 short bits of DNA (“primers”) to fish out the measles virus DNA. The primers bind to a DNA sequence that is complementary to their sequence and an enzyme that is also added, amplifies the stretch of DNA that is between the two primers. After the PCR, the product of the reaction is visualised on an agarose gel that tells you a) whether you have a product and b) what size it is. Quite often, instead of the one product you predicted, you’ll have more or none and you then have to play around with the temperature and cycle lengths until you get your desired result (in comparison to a positive control of which you are 100% that it contains the measles virus). Still, the gel will only tell you that there is a product and not whether the DNA sequence of the product is that of measles virus (or some other gene/DNA bit that happens to contain a stretch similar to your primers). This is what the authors did: they cut their PCR products out of the gel and analysed the DNA sequence of the entire PCR product and found that the sequence that had been amplified was not measles specific.

    Additionally, they tested how much anti-measles antibodies the autistic children and neurotypical controls had (assuming that a chronic infection with measles virus in the gut would lead to very high antibody titres against measles) and found that there was no difference between the groups.

    (scratches her head) does this make more sense?

    Catherina

  22. María Luján October 5, 2006 at 14:32 #

    Hi Kev
    I have prepared a comment about Dr Ward et al. It is long.Do you agree I post it here?
    Thank you in advance
    M. Luján

  23. Kev October 5, 2006 at 15:22 #

    I’d be surprised if it wasn’t long from you Maria ;o)

    Go right ahead but don’t worry if it doesn’t appear straight away, if there’s a lot of links I might need to authorise it.

  24. MAría Luján October 5, 2006 at 19:29 #

    Hi Kev, I have just sent an e-mail to you.
    Hope you receive it.Thank you

  25. LB October 6, 2006 at 00:10 #

    My son did develop normally until age 3 (somewhat advanced actually) however has received diagnosis of autism, PDD-NOS and one who suggested AS but said he presented as a child with autism. So does there seem to be confusion within the medical community in general and CDD is STILL under the PDD umbrella so it isn’t entirely different. Classifications really seem to be loose because kids with language delays are getting dx’s of Asperger’s too even though they do not fit the critieria. So how important are the criteria vs being under the umbrella of PDD – and what of those who seem to have ASD in the family but produced a child with regressive autism if it different?

  26. HN October 6, 2006 at 02:35 #

    LB… do not worry about it, you are right in that it seems ASD or PDD is being bandied about as this huge umbrella.

    You might try going to a good child neurologist who could give you some more definitive answers. Or not.

    My oldest child has a severe speech disorder. When he was three years old he only communicated with sign language. His diagnosis from the neurologist and speech pathologist was oral motor dyspraxia (which may or may not be related to a history of seizures).

    Just this year at his (hopefully final) three year psych evaluation for special ed. services at the school was the FIRST time anyone suggested using the “autistic” label on him. It was from the school psych (who admitted she was not qualified to diagnose him). By the way, he is 18 years old.

    Yes, there is confusion in diagnoses (though truthfully true mercury poisoining is completely different!)

  27. Brian Deer October 6, 2006 at 21:34 #

    Some of the Wakefield/O’Leary MV info sought is in this report:

    http://briandeer.com/mmr/oleary-pcr.htm

    However, this only scratches the surface of what happened.

  28. David N. Andrews MEd (Dec 2006) October 7, 2006 at 08:06 #

    Hi LB…

    “My son did develop normally until age 3 (somewhat advanced actually) however has received diagnosis of autism, PDD-NOS and one who suggested AS but said he presented as a child with autism.”

    In that case, they should have considered the Heller diagnosis, at least for elimination.

    “So does there seem to be confusion within the medical community in general and CDD is STILL under the PDD umbrella so it isn’t entirely different.”

    Not necessarily. Two radically different diagnostic categories can fall into the same group because of certain characteristics they share: in this case, we’re talking about two types of developmental issue which have an effect on many aspects of the life of the person who’d get the diagnosis… hence being under the same umbrella, but still being two different things.

    “Classifications really seem to be loose because kids with language delays are getting dx’s of Asperger’s too even though they do not fit the critieria.”

    It’s not so much the classifications… if they get too tight, they become useless in the same way that they would if they were too loose. Much of it is due to laxity of practice by the diagnostician. In clinical practice, it is not such a problem for a diagnostician to allow the diagnosis if the diagnosee presents with something that is significantly similar to the category being diagnosed (e.g., Gillberg stating that the diagnosis can be allowed in clinical practice if the social interaction area in his ASDI is fulfilled, but only four of the remaining five areas are fulfilled); but, in a research diagnosis, the practice is different: all areas must be fulfilled. I like to make a diagnosis as per research standards if at all possible, because then it is unequivocal, and practically impossible to argue against. However, some clinicians are quite lax in their thinking: in one case I know, strong special interests are being seen as obsessions, despite the clinical definition of an obsession as being a thought which is ‘recurrent, disturbing and causes anxiety’. Without those characteristics, the thought is not an obsession, in clinical terms.

    “So how important are the criteria vs being under the umbrella of PDD – and what of those who seem to have ASD in the family but produced a child with regressive autism if it different?”

    The criteria are very important, because they give an idea of what a diagnosee’s needs are likely to be. Two links: http://www.patient.co.uk/showdoc/40002248/ and http://www.patient.co.uk/showdoc/40000711 … the first is for Heller’s syndrome and the second is for the Kanner-Asperger spectrum of autism. Of particular interest is this, from the Heller link: “Patient shows similar social and communication deficits as those associated with autism. However, it is clearly distinguishable from autism on the basis of the normal antecedent developmental history.”

    NM said:”Yes, there is confusion in diagnoses (though truthfully true mercury poisoning is completely different!)”

    And this is the issue in mercury poisoning: “Mercury (toxic dose for mercury compounds is about 10-50mg/kg). Mercury is poorly absorbed from the gut and ingestion is usually harmless (unless aspiration occurs). A single dose (eg broken thermometer) usually causes no problems. It is only slowly absorbed through the skin but can cause a contact dermatitis.
    In the mid 1950 – 1968 the people of Minamata, Japan suffered chronic mercury poisoning from pollution from a local factory (Minamata disease). “Mad as a Hatter” is derived from poisoning among hatmakers who used mercuric nitrate to soften the hair of animal hides.

    Acute poisoning: (inhalation) causes an acute pneumonitis (± ARDS), flu like symptoms, irritability, myalgia and GI upset. Subsequent peripheral neuropathy, hepatic dysfunction or renal failure may develop.

    Chronic poisoning: irritability, personality changes, headache, peripheral neuropathy, memory problems, ataxia, coma, respiratory problems (pneumonitis and ARDS), gastrointestinal upset (abdominal pain, gingivitis and stomatitis, nausea, vomiting). Renal problems include ARF, nephrotic syndrome and ATN. (http://www.patient.co.uk/showdoc/40001401)” (ARDS: acute respiratory distress syndrome)

    Totally different from either Kanner-Asperger autism or Heller’s syndrome.

  29. David N. Andrews MEd (Dec 2006) October 7, 2006 at 08:34 #

    Kevin… something weird happened there with a font setting from a Cut-n-Paste thing, and I can’t get back in to edit the thing. Do you know how to alter that font? :/

  30. LB October 7, 2006 at 16:26 #

    David – Thanks for the information. This is what is confusing not only to me but to other parents as well – and often because of the questioning are labeled themselves as curebies in denial of their child’s autism. CDD is NOT being used much as a diagnostic catagory even if it is on the books and that has been debated more than a few times in parent groups. In doing our own research I had requested that my son be tested for Landau Keffler because that seemed to be an option. However I have since found out that testing for that is also innacurate.

    However, I also do not want to get into playing the “real autism” game that some in the mercury only crowd do by redefining what autism is supposed to be. Sometimes I wonder in looking back it seems like my son may have had what I would consider postive signs of AS – like excellent memory and ability to read at a very early age. Another person mentioned Fragile X to me before because of my issues and the fact that I have a daughter with MR but I have not fully looked into that yet.

  31. HN October 7, 2006 at 20:12 #

    Landau Keffler Syndrome is related to seizures. That often requires a sleep EEG, which is not always easy to get. My son was tested for it since he did have a history of seizures.

    I have met one child who did have LKS, but his seizures were indeed causing him severe impairments. He had to have surgery to stop the seizures.

    Have you looked into hyperlexia?
    http://www.hyperlexia.org/ … One of the interesting experiences of having a child in a special ed. program were the birthday parties. At my son’s 5th birthday the hyperlexic child walked through the house reciting Beatrix Potter.

    Also… David, thanks for the interesting read (I can only go on anecdote).

  32. LB October 7, 2006 at 22:46 #

    Thanks HN – Interesting reading on hyperlexia and will research it more thoroughly.

  33. Kev October 13, 2006 at 09:27 #

    Bart Cubbins video look at the MMR issues. Recommended for laypeople.

Trackbacks/Pingbacks

  1. Left Brain/Right Brain » MMR and statistics and science - October 16, 2006

    [...] Now that we have a couple of clinical papers refuting the findings of Wakefield, Krigsman, O’Leary et al – and not only refuting them but even showing exactly how they screwed up – I thought a retrospective look at the data concerning the fall in uptake of the MMR vaccine corresponds to the latest data on prevalence for autism in the UK and what it might mean for the MMR theory. [...]

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