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Peruvian Hamsters and Autism: Cui Bono?

Some people are very invested in the idea that thimerosal in vaccines causes autism. They have looked and looked, but have been unable to find enough credible evidence to convince the scientific community. Thimerosal was removed from US vaccines several years ago, and you might have thought that would end the debate. It didn’t. The spotlight has shifted to other countries that still use thimerosal-preserved vaccines, such as Peru.

Anti-vaccine activist David Kirby said,

If thimerosal is one day proven to be a contributing factor to autism, and if U.S. made vaccines containing the preservative are now being supplied the world over, the scope of this potential tragedy becomes unthinkable.

The anti-vaccine website Age of Autism accuses US policy of

[making]…Kirby’s nightmare suggestion a reality. U.S. vaccine manufacturers have continued to ship thimerosal containing vaccine formulations all over the world, in effect offering a defiant double standard of mercury risk for infants from rich countries as compared to poor countries.

They accuse the US of keeping its own children safe while callously endangering children in other countries. Actually, the decision to remove thimerosal from vaccines in the US was a bend-over-backwards-cautious political decision rather than one based on evidence of harm. The vaccines used in Peru are not evidence of any evil plot, much less a US plot. The World Health Organization (WHO) and its Latin American partner the Pan American Health Organization (PAHO) decided to retain thimerosal as a vaccine preservative because of economic considerations and because they did not find evidence that it was harmful.

The Age of Autism website is making much of a new Peruvian study in hamsters that allegedly supports the thimerosal/autism link. The abstract is available in English, but the full article is in Spanish. Critics demanded an English translation to allow for proper peer review, only to be told they were prejudiced against Spanish and that the report had been peer reviewed. One critic thought “the fact that there is no formal translation of this report into any language that I am aware of makes it obvious that the report is no good – otherwise the scientific community would be falling over themselves to translate it.” I don’t think that’s a valid inference, but anyway it would be nice to be able to read the whole paper, not just the English abstract.

No problem. I’m fluent in Spanish. I read it. The research was not in my field of expertise, but it looked quite reasonable as far as I could tell. I don’t think it really matters whether the study is flawed, because even if its results are impeccable I’m not impressed that they tell us anything that would link thimerosal to autism.

The abstract says

The administration of thimerosal in doses equivalent to vaccines content was associated with low corporal weight, low encephalon weight and smaller stature in postnatal hamsters. Neurotoxic effects were also produced at encephalic level, at hippocampus (regions CA1, CA3, DG), cerebral cortex and cerebellum (Purkinje cells and granuloses cells) with decrease in neuronal density, neuronal necrosis, axonal dismyelinization and gliosis.

A US study in 2004 showed that only certain strains of mice were susceptible to thimerosal, and the findings in those mice were very different from the hamster findings.

Autoimmune disease-sensitive SJL/J mice showed growth delay; reduced locomotion; exaggerated response to novelty; and densely packed, hyperchromic hippocampal neurons with altered glutamate receptors and transporters. Strains resistant to autoimmunity, C57BL/6J and BALB/cJ, were not susceptible. These findings implicate genetic influences and provide a model for investigating thimerosal-related neurotoxicity.

A similar US study on those SJL/J sensitive mice was published in 2008. It used a dose 10 times higher and found that

results do not indicate pervasive developmental neurotoxicity following vaccine-level thimerosal injections in SJL mice, and provide little if any support for the hypothesis that thimerosal exposure contributes to the etiology of neurodevelopmental disorders.

So of the 3 studies in small critters, one showed no effects at 10 times the dose, and the two that did show effects didn’t show the same effects. For instance, one showed a decrease in neuronal density, the other showed densely packed neurons. They did both show growth delays (weight and height), but that is not characteristic of autism; and the other hamster and mouse findings do not coincide and do not match known findings in autism.

Animal studies are always problematical. The effects on hamsters may be very different from the effects in humans. There is no adequate animal model of autism.

The Peruvian study is not listed on PubMed, which does list many journals in other languages and provides English abstracts. It was published in an in-house journal, a publication of the Peruvian medical school where the research was done. Their articles are reviewed by an in-house editorial board, not sent out for external peer review.

Studies in non-English speaking countries are statistically more likely to be positive (i.e., there is a greater chance that published reports are false positives). Scientific standards may not be as high, and negative results are less likely to be published. I don’t think Peru does a whole lot of medical research; this is the first study I have ever read from that country.

The review of the literature in the introduction to the study is biased. It misrepresents the state of the evidence for and against thimerosal. It cites a series of papers as evidence that thimerosal causes autism, but every one of them is by the discredited anti-vaccine activists Geier and Geier. The many credible studies showing no correlation are barely mentioned in passing. It seems obvious that the authors of this paper have an agenda: to show that thimerosal should be removed from vaccines in Peru.

They do not make it clear that the decision to remove thimerosal from American vaccines had nothing to do with any documented dangers, but was a precautionary measure to reduce total mercury burden from all sources “just in case.”

Their bias is also shown by their comments, “While it is true, it is very difficult to extrapolate these findings to other animal experimentation groups and over human beings, our results, as the multiple scientific evidence recently published about thimerosal, clearly indicates the toxic nature of this substance at the same dose and the same chronology as human immunizations; therefore we suggest the employment of alternative preservatives in vaccines, especially those intended to pregnant women, neonates and small children based in the prevention and precaution principles of all medical interventions.”

The best scientific studies usually end with a statement to the effect that “if” their findings are confirmed, it “might” mean thus and so. These folks seem to me to have gone beyond the science into recommending social policy. And they have not considered whether there might be any downside to demanding alternative preservatives.

If the thimerosal hypothesis were correct, the rate of autism would be rising faster in Peru than in the US. I don’t think anyone has tried to determine if that is true. Without that kind of data, conclusions based on animal experiments are nothing but speculation.

So what do we have? One study showing thimerosal is bad for hamsters in a way that doesn’t match the findings in autistic children. One study showing thimerosal is bad for one strain of susceptible mice, but in a different way that also doesn’t match the findings in autistic children. Another mouse study contradicting the first one, showing 10 times as much thimerosal is not bad for mice, even the most susceptible strains of mice. That sure doesn’t add up to much. We may have learned something about hamsters, but we haven’t learned anything about humans or autism.

I think the Peruvian experiment may have been a waste of hamsters. PETA wouldn’t approve. But then PETA wouldn’t approve of the Peruvian policy towards guinea pigs, either: they let them run free on the dirt floor of their kitchens, then snatch them up and cook them as needed. I tasted “cui” when I visited a village in the Andes – it was pretty good.

After reading this study, I couldn’t help but ask, “Cui bono?”
(That’s Latin for “who benefits?” and also for “Does the guinea pig taste good?”)

Posted in: Neuroscience/Mental Health, Vaccines

Leave a Comment (24) ↓

24 thoughts on “Peruvian Hamsters and Autism: Cui Bono?

  1. Joe says:

    P.E.T.A. … Peruvians Eating Tasty Animals?

  2. David Gorski says:

    If the thimerosal hypothesis were correct, the rate of autism would be rising faster in Peru than in the US.

    Actually, if the thimerosal hypothesis were correct, the rate of autism would currently be falling rapidly in the U.S., given that there has not been more than a trace amount of thimerosal in any early childhood vaccine other than the flu vaccine since early 2002; that autism is typically diagnosed between ages 2-4; and that there are thimerosal-free alternatives to the flu vaccine that are being rapidly adopted.

    In any case, this study reminds me of the infamous “monkey study” that is currently being circulated as “evidence” that the current vaccine schedule in humans is toxic: Bad science using an irrelevant model and coming to unjustified conclusions in the service of an antivaccine agenda.

  3. notmercury says:

    I’ve tasted Guinea Pig before but never Peruvian Hamster. I wonder if the Sucrose group would taste sweeter than the Saline group.

  4. isles says:

    I wonder if anti-vacciners realize how silly it makes them look to be reaching for this dubious stuff from faraway when there’s such excellent science, and so much of it, right in front of their faces.

  5. Karl Withakay says:

    It is amusing how the anti-vaxers will trumpet one or two poor quality (usually extremely biased) studies as proof of their position, but will ignore the warehouse of good, scientific studies that refute their claims. You’d think a group that so ignores good science wouldn’t bother with studies at all.

  6. Fifi says:

    Karl – Ah, but pseudoscience is all about creating the impression that one’s concepts are based in science and therefore the real world (ie. not scams). Most people respect science enough that a study lends authority for them even if they don’t really understand the process or the study itself – hence the reason why everyone from IDers to supplement manufacturers use pseudoscience to promote their products.

  7. JKW says:

    I like your post but I was wondering about this:

    “Studies in non-English speaking countries are statistically more likely to be positive (i.e., there is a greater chance that published reports are false positives).”

    Do you have a cite? I mean, it wouldn’t surprise me if articles published in non-English-only journals were sub-par.

    It also appears to me that this “research” is the med school equivalent of a freshman’s essay for a lit class. They were all bounded together and a student from the art department designed a cover.

  8. Harriet Hall says:

    There’s an article by Vickers et al entitled “Do certain countries produce only positive results? A systematic review of controlled trials.”
    http://www.ncbi.nlm.nih.gov/pubmed/9551280

    I’ve read elsewhere that studies out of China are essentially all positive, but can’t put my hands on the source at the moment. Maybe other readers can help.

    I also found this on bias in Chinese genetic epidemiology studies: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371%2Fjournal.pmed.0020334&ct=1

  9. Jules says:

    A sort of roundabout story:

    I don’t remember the last time I went to the dentist, because it’s been that long. But I do remember that it was about the time when composites were starting to come in as the filling material of choice. My dentist, being slightly behind the times, stuck four little blobs of mercury amalgam in my teeth.

    They’ve been with me for at least 16 years (since that last visit I’ve managed to avoid cavities and so haven’t been back since). My boyfriend, who has both amalgams and composites, has had to get his composites replaced almost every year, while his amalgams remain intact.

    Moral of the story: stick to the mercury! :-P

    In all seriousness–I think people are clinging to the pseudo-autism-thimserol link because they don’t want to acknowledge a far likelier culprit: TV. I’m about halfway convinced that the correlation between TV and autism rates is real, but I haven’t heard of any long-term studies or anything beyond the Cornell epidemiological survey that first uncovered this link. Like I said, I’m not entirely convinced–correlations are not causations–but it’s intriguing and (I think) worth exploring. The theory (which is far more sound than anything the anti-vax idiots can come up with) is that watching lots of brightly-colored two-dimensional images when the brain is still developing can lead to changes in how the visual cortex develops, which correspond to the differences in the visual cortices of autistic kids. Like I said, intriguing. But real? TBD.

  10. weing says:

    Could the vaccine manufacturers benefit selling more doses of the expensive single dose vials?

  11. Joybobington says:

    Off-topic but, a Spanish language radio station in Puerto Rico aired a program last Sunday recommending trepanation for Austistic children but I was unable to get the name of the people and ‘doctors’ involved.

    Has anyone else heard anything like this being done before? At what point can we call child services on these people?

  12. Harriet Hall says:

    I found this on the Internet:

    “Some things deserve special mention just because they go off the deep end. Virginia Gomez deserves an honorary mention for achievement in the field of insanity. As you can see in her horrifying website this is a person who dabbles in every field of pseudoscience, woo and superstition imaginable. I first became aware of Virginia through her radio program on WKAQ 580, a Spanish language station in Puerto Rico.

    Last week the program hit a new low, when her guest, (a psychologist who I have been unable to identify), recommended trepanation as a treatment for autism. This bears repeating, her guest recommended trepanation as a treatment for autistic children. In keeping with her practice of agreeing with anything her guests say regardless of lack of plausibility of corroborating evidence, she promptly told the caller to look into trepanation as treatment.” http://doazic.wordpress.com/

    There is even an International Trepanation Advocacy Group that believes that making a opening in the skull favorably alters movement of blood through the brain and improves brain functions. http://www.trepan.com/index_.php

  13. Joybobington says:

    It looks like Dr. Luis Maya who authored the study is a Doctor of Internal Medicine.

    A bit of google-fu found this website:
    http://members3.boardhost.com/AUTISMO/msg/1181658890.html

    Which shows that he apparently ‘treats’ autistic children. (website also has the address of his office and his phone number). Some more googling shows that he is lobbying the government of Peru to stop using vaccines that contain ‘toxic levels of mercury’.

    More googling finds this website for a forum on “Biomedical Treatments for Autism” in Venezuela, where Dr. Maya is a guest speaker:
    http://www.greatplainslaboratory.com/Conference/VENEZUELA-2008/

    So it does look like this guy is out to make a quick buck off those who believe autism is caused by mercury.

    Shameless link to my blog: doazic.wordpress.com

  14. AntiVax says:

    “They have looked and looked, but have been unable to find enough credible evidence to convince the scientific community. ”

    LOL! You mean the scientific community that needs vaccines to be safe and effective. http://www.whale.to/vaccine/vaccine_autism_proven.html

  15. TsuDhoNimh says:

    Here is one problem with the hamster study: A los grupos B y C se les administró por vía intramuscular tres dosis equivalentes de sucrosa y timerosal, respectivamente, en los días 7 (0,227 µg/dosis), 9 (0,216 µg/dosis) y 11 (0,220 µg/dosis) del nacimiento, en un volumen de 20 µL de suero fisiológico.

    Giving an equivalent dose at days 7, 9, and 11 for the hamster pup (trying to match 2, 4, and 6 month infants) doesn’t give the animal time to clear the first dose before the second one is given. The infants have a couple of months; the hamsters have 48 hours.

    Like rats and mice, hamsters are born naked and blind. Their eyes don’t even open until day 13 or 14 …. so these “experiments” were done on extremely immature animals.

    I see no mention of equal numbers of sexes in the groups, and hamster females are larger than the males by about 10%, even before weaning.

    I see no mention of the light levels or the care conditions. Hamsters are photo-period sensitive, and changing light levels will make them gain or lose weight.

  16. Jim1138 says:

    Jules: an amalgam is a mixture of mercury with one or more metals. If you had mercury amalgam fillings, you might want to check ’cause they probably aren’t there anymore.

    I do have some composites that are 18 years old. The dentist apparently did not cure them completely. I had a bad case of glossitis for weeks until the dentist went over the composites again with the UV gun. These predated the blue light cured composites. Mercury free is not necessarily toxin free.

  17. javier_villafuerte says:

    Dr. Luis Maya is, as some of you pointed out, a physician specialized in internal medicine and not a neurobiologist. He is also a well known anti-vaccine activist in Peru, a country that, as you pointed out too, publishes a small amount of biomedical research for the size of its population.

    I am a bit surprised that some of you point out as arguments against Dr. Maya’s research things like the fact that it’s done in a country like Peru or that it’s written in spanish. That kind of ethnocentric bias resembles a lot Dr. Maya’s anti-vaccine bias.

    Peruvian researchers have made significant contributions to many areas of medicine such as infectious diseases (cysticercosis, leishmaniasis, bartonellosis, etc), gastroenterology (h pylori and gastric cancer), high altitude medicine and physiology, among other disciplines.

    Pseudoscience is diffused through the media not only in underdeveloped spanish speaking countries like Puerto Rico or Peru but also in well developed countries. (ie. scientology, the “abscence of evidence” for global warming…) The industry bias of many well renowned medical journals from the developed world is not too hard to be detected… So if you have money and influence peer review may not only by-passed in Peru but also in Europe or the US…

    So it would be great if the discussion were based a lot more on the critical appraisal of Dr. Maya’s research (like TsuDohNimh’s arguments) than in speculations about what goes on in Peru or Puerto Rico.

    PD: There’s a comprehensive academic review about Thimerosal and autism written by a peruvian pediatrician. Which was also published in spanish in the Acta Medica Peruana, here’s the link:
    http://www.scielo.org.pe/scielo.php?script=sci_arttext&pid=S1728-59172007000100012&lng=es&nrm=is

    Javier Villafuerte Galvez, peruvian medical student

  18. Harriet Hall says:

    There is a difference between ethocentric bias and acknowledging the simple fact that studies in many non-English speaking countries are more subject to publication bias and other factors that lessen their average credibility. Studies from an internationally recognized research entity with a good track record, published in a journal with high standards like the New England Journal of Medicine, are statistically more likely to be good science than the average study published in a 3rd world country in an obscure journal. In this case, the way the report was written showed bias on the part of the researchers.

    That said, each study should be judged on its own merits. Good research and bad research are done in all countries.

    In this case, even if this study’s design and results were impeccable, even if it were done at Johns Hopkins and published in The New England Journal, even if ithe authors were Nobel-prize winning researchers, it would not be acceptable to use it as an argument against thimerosal in vaccines.

    I intended no disrespect to Peru or to Spanish-speaking scientists. My disrespect is for those who grasp at straws like this to support an ideological agenda.

  19. javier_villafuerte says:

    The viewpoints that seemed disrespectful to me were actually not those in your initial post but those by some of the replies to your post.

    I’m not too sure about the references used to support the hypothesis that non-english speaking countries or journals publish positive studies preferentially. The first study cited compares studies about acupuncture between England on one side and China, Japan, Russia and Taiwan on the other…it might not be too wise to generalize from that kind of study.

    Nevertheless I believe, just like you, that that RCTs conducted in ‘developing’ countries are likelier to be positive (even if I don’t have any evidence to support it, is there any?). I also believe that this could be explained by the cost of conducting proper RCTs (according to the regulations to protect patients rights), which is so high that it’s unlikely for non-industry-linked researchers to finance an RCT. Drug companies or medical technology companies pay for positive results to appear and negative ones not to, that’s no mystery.

    Anales de la Facultad de Medicina is not considered an obscure journal here, it’s edited at the oldest medical school in the country and one of the most prestigious. I don’t know about it’s peer review process, though. I know that at least 2 peruvian medical journals (Revista Medica Herediana and Revista Peruana de Medicina Experimental y Salud Publica) have due peer-review processes.

    I think, as most of you do, that research should not be biased by our personal beliefs. Dr. Maya’s paper does have very biased introduction and has the methodological flaws pointed out by many of you.

    I am myself also very disturbed by some anti-vaccine activists acts and opinions. Recently in Peru there have been 2 very important vaccination campaigns. The first one was to vaccinate fertile women to prevent congenital rubella and the other one to vaccinate all children against Hepatitis B Virus (we still have regions with high vertical transmission rates).

    Both of these campaigns were attacked through the media by anti-vaccine activists. The negative impact of this on both campaigns is still to be assessed by a scientific manner but I witnessed many parents refusing to vaccinate their children fearing autism. In a country where most HBV infected patients won’t be able to afford inferon or antivirals it’s even more serious to harm vaccination campaigns like these ones.

    Misinformation through the media harms the health of populations. Those who misinform should be legally prosecutable for the harm they provoke.

    On the bright side, the Peruvian Ministry of Health did not withdraw its vaccination campaigns despite all the media fuss. But this is thanks to politicians that were well informed by serious physicians.

  20. Harriet Hall says:

    Javier said,

    “I’m not too sure about the references used to support the hypothesis that non-english speaking countries or journals publish positive studies preferentially. The first study cited compares studies about acupuncture between England on one side and China, Japan, Russia and Taiwan on the other…it might not be too wise to generalize from that kind of study.”

    The acupuncture study I cited went on to evaluate studies of conventional treatments. The abstract says “In studies that examined interventions other than acupuncture, 405 of 1100 abstracts met the inclusion criteria. Of trials published in England, 75% gave the test treatment as superior to control. The results for China, Japan, Russia/USSR, and Taiwan were 99%, 89%, 97%, and 95%, respectively. No trial published in China or Russia/USSR found a test treatment to be ineffective.”

    Granted, one shouldn’t usually generalize from one study. But my personal experience and reports from credible sources in China make me think that the conclusion is probably valid. In the absence of any other study refuting its findings, I tentatively accept it.

  21. TsuDhoNimh says:

    Javier –
    Thanks for the link.

    If a professor thinks his students have discovered something remarkable, it’s his duty to encourage them to get it the widest possible audience, not bury it in the school’s own publications.

    That might mean submitting to publications outside his sphere of influence, to a journal with higher circulation and stiffer standards.

  22. Joybobington says:

    In case anyone was still googling Dr. Perez:
    http://www.greatplainslaboratory.com/Conference/VENEZUELA-2008/

    He was down in Venezuela with none other than Andrew Wakefield this May.

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