Experts comment on Hornig et al.'s MMR paper

6 Sep

It’s been interesting reading the news reports following the Hornig MMR/regression/bowel-disease study. That has been picked up by most major outlets (and minor outlets). It has been extensively blogged (Kev, Orac, Kristina, Anthony, Steve, Phil (bad astronomy), to name a few).

I have enjoyed reading the various experts that have been brought in to comment on the paper. I list some of them here.

CNN

“This really puts this issue to bed,” said Andy Shih, vice president for scientific affairs of “Autism Speaks,” an advocacy group.

ABC News

Dr. Marie McCormick of the Harvard School of Public Health said these results are definitive and significant.

“This is the nail in the coffin,” she said. “The final bit of research we were looking for to finally discredit this link between the measles vaccine and autism” is proven. But there have been dozens of studies over the years debunking a link between vaccines and autism and the controversy has still continued.

WebMD

“This really closes the scientific inquiry into whether measles or MMR vaccination causes autism,” Schaffner tells WebMD. “It is convincing because it takes the original concept of the profoundly flawed [earlier] study and does it the way it should have been done the first time.”

One of the most amazing parts of this event was the participation of Mr. Rick Rollens. Scientific American included some of Mr. Rollens’ statements:

Rick Rollens, who has an autistic son who suffers from a “horrible bowel disorder,” called the new research sound science and praised it for calling attention to an underserved subset of the autism spectrum: those children who also suffer from GI problems. But he insists that it does not give the all clear to all vaccines.

“I’m totally convinced that a vaccine caused the autism my child suffers from,” Rollens says. “This study by itself does not exonerate the role of all vaccines”—only the MMR.

On the stranger side (is it possible to get stranger than using Rick Rollens’ quotes in support of a study unlinking a vaccine from autism?), Sallie Bernard, quoted at WebMD states

“On the plus side, this study has shown a link between gastrointestinal distress and regression in autism,” Bernard tells WebMD. “A lot of people don’t accept this and deny parents’ perspective when they say their kids’ with autism have GI trouble.”

I call this one strange because (a) the study didn’t show this link and (b) she complains that the study size is too small to be significant. Too small for the parts she doesn’t like, just fine for the conclusions she wants to create.

What’s missing so far is a statement from some of the people whom we all expect to not accept this study. The good people at the Age-of-Autism have warned us that they have a “powerful response” from Mr. Olmsted coming out on Friday. It’s 11:38 now on the west coast, I’m gonna go out on a limb and say it didn’t happen. Julie Deardorff (Julie’s Health Club, a blog run by the Chicago Tribune) skipped past it and blogged about the vaccine uptake data that came out the next day. Sharyl Attkisson…well, it doesn’t seem to be on her radar that yes, indeed, researchers have not turned their backs on the question of vaccines and autism. Yes, indeed, they are looking at “the children that got sick”. Odd, since she has a vaccine-oriented blog post dated Sept. 4. It would have been very easy to include this new study there. I guess correcting her old stories wouldn’t be much fun.

What is fun, and totally off topic, was a bit from this blog post by Ms. Attkisson. She was complaining that the CDC wastes money. She talks about

“…grants being awarded to projects that investigators have found in some cases to have “no objectives,” are “not performing,” or have been rated as “abysmal.” In other cases, grants have gone to community-based groups with very little oversight.”

I hope she (and others) apply similar rules when considering whether to include projects in the IACC’s Strategic Plan that are likely to be rated “abysmal”, or are expected to be “not performing”.

I wonder how she would feel about hundreds of thousands of dollars in pork sent to one of autism’s alternative medical groups with no oversight, no results.

Well, I’ve wandered off topic. It is 11:59 and still no “powerful response” from Mr. Olmsted. Time to hit “publish”.

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17 Responses to “Experts comment on Hornig et al.'s MMR paper”

  1. MariaLu September 6, 2008 at 14:35 #

    I have two main groups of concerns, Kev. I am not an expert, but the mom of an autistic child with a lot of questions
    A) Is Edmonton vaccinal Strain sequences the right measles to test as primers for checking of persistence, years after injection?
    And B)Do we need measles or other neurothropic virus presence/replication to produce an inital immune permanent change that may be related to some inflammatory /other situation in gut that affects brain?

    http://www.nature.com/labinvest/journal/v87/n8/pdf/3700600a.pdf

  2. MariaLu September 6, 2008 at 14:36 #

    Sullivan, sorry

  3. Sullivan September 6, 2008 at 16:54 #

    Maria,

    I’m not sure if I am answering your question (a) correctly here, but did you read the appendix S1? They tested the primers to detect both vaccine and wild-type vaccine strains:

    Testing by real time RT-PCR demonstrated the capacity of the new primer/probe sets to detect vaccine strain and wild type sequences associated with outbreaks of human disease (data not shown).

    Also, they note specifically two wild-type strains that were validated:

    Assay performance characteristics were validated using viral nucleic acid from three measles isolates: 1) vaccine strain virus (Moraten, a derivative of the Edmonston seed B strain; 2) MVi/Beijing.CHN/94-1 (Chinese wild type isolate); and 3) MVi/Reuler.LUX/17.96 (European wild type isolate). Standards were cloned for each of the respective gene target regions of these MV isolates.

  4. TheProbe September 6, 2008 at 16:56 #

    The reason why you did not get “The Pwer” is that two very POWERFUL storms in the Atlantic blew the Olmsted effluvia right back to California.

    Remember, Olmsted is the so-called investigative journalist who went to Amish Country here in the States, and could not find any autistic kids. Of course, the fact that he neglected to go to the Clinic for Special Children where they are treated did not mean much to him.

  5. MariaLu September 6, 2008 at 17:14 #

    Hi Sullivan
    Thank you for the mention of the wild strains. from S1 However, no mention of the length of the sequence is included. AND if the strain is mutated, why is it going to match with the selected wild/vaccinal strains?
    The persistence is not so rare as could be thought
    J Gen Virol. 1995 Dec;76 ( Pt 12):3201-4.
    Detection of measles virus nucleoprotein mRNA in autopsied brain tissues.
    Katayama Y, Hotta H, Nishimura A, Tatsuno Y, Homma M.
    Department of Microbiology, Kobe University School of Medicine, Hyogo, Japan.
    By means of RT-PCR, a portion of measles virus (MV) mRNA encoding nucleoprotein (NP) could be detected in 11 (18%) of 61 brain tissue samples obtained from administrative autopsy cases, who apparently had not suffered from subacute sclerosing panencephalitis (SSPE)-like central nervous system disorders. Most of the brain-derived NP sequences showed significant asynonymous nucleotide substitutions when compared with wild-type MV isolates and SSPE virus. Our present results suggest that MV commonly persists in the human brain without causing apparent clinical symptoms, probably due to decreased virus replication.
    J Clin Microbiol. 1998 Jan;36(1):299-301.
    Detection of measles virus mRNA from autopsied human tissues.
    Katayama Y, Kohso K, Nishimura A, Tatsuno Y, Homma M, Hotta H.
    Department of Microbiology, Kobe University School of Medicine, Hyogo, Japan.

    By reverse transcription-PCR, measles virus (MV) mRNA was detected in the brain, kidney, spleen, liver, and lung tissues obtained from 23 (45.1%) of 51 autopsy subjects, with the detection rates of each tissue ranging from 8 to 20%. Sequence analysis revealed frequent mutations in the corresponding viral protein. These results suggest that MV mutants commonly persist in apparently healthy individuals

    MV mutants….

    All is about persistence checking . But if there is persistence there is virus replication and if there is replication of measles RNA there is mutation of the sequence –whetever the place-therefore why they use primers of the original vaccinal strain instead of the techniques that are used to amplify potential unknown sequences-unknown RNA virus-, with complete sequencing and comparison with known detected RNA Viruses-different measles sequences? Dr Wakefield´s team used short sequences – with all the problems cited in methodology but being shorter it was unespecific BUT perhaps that was the reason of being positive for example Kawashiwa et al-that made cDNA step that Souza didn´t; Other used longer sequences- but of the Edmonton vaccinal strain but the patients were different-even ages were different-. Souza didn´t use the SAME approach.

    Let me to present you the idea that concerns me-although I am open to the possibility of being wrong of course.They –ALL-are checking supposed persistence using primers of a vaccinal strain – considering in advance that it was the same that injected, years after injected. Therefore they are searching for a frozen virus sequence that did not mutate and they say that they check for persistance-that implies replication ??? With the rate of MV mutation? You need cleareance of MV through an adequate imumune answer …but even in that case there is mutated MV found?
    How the immune system avoids persistance and assure cleareance and how manage to avoid negative impact of the mutated MV found in healthy people?

    But if it persisted, it replicated and it mutated and if it didn´t replicate it didn´t mutate and then didn´t persist therefore WHY TO search for unchanged EDMONTON VACCINAL STRAIN with Primers of Edmonton vaccinal strain for PERSISTENCE-YEARS after injection-or selected wild strains – instead of Recovering with Multiplex PCR- considering coinfections (Human DNA is the only thing to recover from the gut of autistic children with the coinfections of viral-herpes-fungal/bacterial infections they are reported to have?) or other advanced techniques used to unknwon? What about the wild infections management?
    Why NOT other advanced techniques to recover unknown RNA viruses–and full sequencing-such as it is done with new genetic variants of RNA measles viruses AND looking for homologous sequences with MV and other RNA virus from the MMR and wild origin from the MMR group? What about coinfections and intereference viral/bacterial/fungal- beyond the contamination in the test?
    All was reduced to Dr Wakefield original question and NO NEW IDEAS were tested.
    With the amount of knowledge accumulated in persistence why to repeat that question once and again and again without the analysis of the question?
    For example

    Virus Res. 2005 Aug;111(2):132-47. Links
    Molecular mechanisms of measles virus persistence.Rima BK, Duprex WP.
    School of Biology and Biochemistry and Centre for Cancer Research and Cell Biology, The Queen’s University of Belfast, Belfast BT9 7BL, Northern Ireland, UK.

    As measles virus causes subacute sclerosing panencephalitis and measles inclusion body encephalitis due to its ability to establish human persistent infection, without symptoms for the time between the acute infection and the onset of clinical symptoms, it has been the paradigm for a long term persistent as opposed to chronic infection by an RNA virus. We have reviewed the mechanisms of persistence of the virus and discuss specific mutations associated with CNS infection affecting the matrix and fusion protein genes. These are placed in the context of our current understanding of the viral replication cycle. We also consider the proposed mechanisms of persistence of the virus in replicating cell cultures and conclude that no general mechanistic model can be derived from our current state of knowledge. Finally, we indicate how reverse genetics approaches and the use of mouse models with specific knock-out and knock-in modifications can further our understanding of measles virus persistence.
    What do you think, Sullivan?

  6. Ms. Clark September 6, 2008 at 20:50 #

    Dr. Rima, lead author of the second paper testified in the omnibus hearing. He said very plainly that he does not believe that vaccine measles cause autism. If wild-type measles could cause autism then why hasn’t it been doing so for thousands of years? The antivax bizarros aren’t interested in wild-type measles because they can’t sue anyone for it. You won’t see the antivax orgs funding research to pin autism on anything but something that can get them money. It has to come from a corporation with lots of money or they are not interested.

    There is no reason to connect viruses living in the guts of children and autism. It’s a stupid idea that was originated by lawyers who were trying to sue vaccine manufacturers. It was also an idea that Wakefield had that measles vaccine caused Crohns disease. He patented his own “vaccine” for measles that was supposed to be not cause this problem.

    Dr. Rima testified to the ridiculous state of the O’Leary, lab, too. It’s all in the omnibus transcripts.

    Maria, why don’t you ask experts who can give you real answers? Why do you want to put out questions among amateurs that will put fear into people about things that you think might happen, maybe. Go ask an expert. If you get a good answer you can share it. If you are told, “that’s not reasonable” then you won’t be filling people’s minds with false ideas of possible scary happenings.

    This totally upsets me. You put these random ideas out there and they could make people decide not to vaccinate while they are awaiting these arcane answers to your arcane questions. Their babies could die of real life measles because you planted a nonsense fear in their minds.

  7. MariaLu September 6, 2008 at 21:18 #

    This is my last answer to you AD.If you can´t answer my question, why then don´t you acknowledge? Why do you think I didn´t ask experts?

    If this blog doesn´t want questions, only have to delete my posts. I put no random ideas in nobody. Parents , we, are much intelligent than you think and nobody is going to- or should- base a decision that should be done with a serious doctor about what a parent- a mom of an autistic child that is not a researcher in Autism and stablished many times so- asking questions posted in a blog
    As the mom of an autistic child who was fully vaccinated being an unknwon at that point IgA atypical defficient, and badly affected by the MMR between many other things- the oversimplification-once and again-from those who make the questions, and answer them and analyzed them and from you is beyond my understanding. I have the right to make questions. If you don´t like them at this point is your problem. If Kev don´t like them only has to delete them.If Sullivan thinks they are irrelevant only has to explain so, if he wants to.

    This is why I am not going to answer you.

    Have a nice life and goodbye.

  8. Ms. Clark September 6, 2008 at 22:12 #

    Maria,

    Why don’t you tell us what the experts said when you asked them about a mutated Edmonton strain?

    Why would it matter? If the Edmonton vaccine strain can mutate so can any other strain. You want them to test autistic kids for every possible variant of measles, mutated kinds that have never been found in the wild, maybe because they might exist?

    That parents are not all intelligent about science is easy to prove. Most Americans will tell you that Argentina is probably somewhere in Africa!

    http://blogs.chron.com/sciguy/archives/2006/05/parents_our_kid.html

    Many of them can’t tell you if the moon revolves around the earth.

    Many of them have no idea what a virus is except that it’s probably a bad thing.
    Americans have signed a petition to ban dihydrogen monoxide.

    I am asking you not to plant useless fears into peoples heads because you want to “talk” about some arcane idea, one of a million that have occurred to you as possibly being related to autism, all of them documented with a dozen abstracts from pubmed. I am not ordering you to do anything, just asking you to think of the consequences of planting fears in people’s heads and the utter pointlessness of asking amateurs esoteric questions about minutia that only an life-long expert would be likely to be able to answer.

    I don’t think it’s an appropriate thing to do.

  9. Ms. Clark September 6, 2008 at 22:25 #

    What is the currency in the United Kingdom?

    “Queen Elizabeth’s money? That’s all I know.”

    Name a country that begins with “U”?
    “Uh, Utopia!”

    What’s the religion of Israel?

    “Catholic probably.”

    How many sides does a triangle have?

    “No sides, Uh, One.”

  10. Ms. Clark September 6, 2008 at 22:27 #

    “I’m listening to what you’re saying but I only hear what I WANT to.”

    Wanna bet she’s an antivaxer, too?

  11. Regan September 6, 2008 at 22:52 #

    Sullivan,
    Are you still waiting for the mighty response from Mr. Olmsted?

  12. alyric September 6, 2008 at 23:02 #

    Strange, but the interviewer for the general knowledege quiz sounded like an Aussie. Now, if he’d done this on the streets of Sydney, would the results have been different? Probably not.

  13. Ms. Clark September 6, 2008 at 23:04 #

    I think one of the interviewer-on-the-streets was from New Zealand.

    You know, New Zealand, it’s that little island country just south of North Korea. :-)

  14. brian September 7, 2008 at 01:38 #

    MariaLu asked: “Do we need measles or other neurothropic virus presence/replication to produce an inital immune permanent change that may be related to some inflammatory /other situation in gut that affects brain?”

    It’s interesting that you asked that question in the context of a discussion of Mady Horning’s work because it happens that Dr. Horning has been interested in prenatal rather than postnatal infection models (e.g., Borna virus infection in mice) of autism for years; that basic idea is supported by numerous publications including recent work that suggests that the immune response to prenatal infection, and not infection per se, may trigger some neurodevelopment changes that can produce autism. Other work, of course, overwhelmingly supports the genetic basis of autism, but the important point is that the anatomical changes observed in the brains of autistic individuals (whether triggered by environmental insults such as prenatal infection/immune activity or prenatal chemical exposure or by genetics) are underway years before a child ever receives an MMR vaccine. The “temporal association” of MMR vaccination with the diagnosis of autism has been terribly misleading. It’s obviously harder for parents to associate behavior with unseen defects (in, for example, white matter, minicolumn architecture, or in the cerebellum) that began in fetal development than to remember that something happened about the time that they first noticed the results of those prenatal problems. The problem with your question is that it ignores the clear evidence that the observed neurodevelopmental changes begin long before exposure to measles virus via vaccination.

  15. Navi September 7, 2008 at 17:28 #

    hmmm no idea about that subset. I think gastro issues in people w/ autism should be researched, though. Not because I think there’s a higher percentage in the regular population but because I think a lot these people can’t tell us if they feel poorly, or if their stomach is bugging them, etc. I certainly imagine that if the person feels better, some of the behaviors mistakenly attributed to autism might improve.

    *luckily my son’s Dr. has finally made a recommendation to a gastroenterologist, after multiple comments about his frequent diarrhea that we’ve already figured out the fad autism diets won’t help, and it’s difficult to pinpoint a specific food because he eats/mouths everything.

  16. Joseph September 7, 2008 at 18:27 #

    Shouldn’t someone who understands science and research methodology write a rebuttal of the paper, instead of Dan Olmsted?

    Seriously, every article by Dan Olmsted that I remember relies completely on anecdotes and just-so stories.

  17. HolfordWatch September 8, 2008 at 16:02 #

    Maria L wrote:

    Why do you think I didn´t ask experts?

    I would be interested to learn what the experts wrote in response to your questions. Or, is the fact that you are posting the questions indicative that you received no response or an unsatisfactory response?

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