Orac was kind enough to pollute my inbox with the latest idiocy from the journal that has never met a crank it didn’t like. As Orac says, “Medical Hypotheses [is] the journal where the editors encourage the authors to make shit up.”

Before I tell you about the latest “hypothesis”, let me give you an idea of what kind of thinking goes into this publication. The latest issue has an editorial that argues that it is the “maverick” scientist who makes the real scientific breakthroughs, and that teamwork is only for the “modestly talented”.

Not that there’s anything inherently wrong with being somewhat unconventional, but “maverick” implies something specific: “a lone dissenter, as an intellectual, an artist, or a politician, who takes an independent stand apart from his or her associates.”

Science works because individuals don’t get to just “make shit up”. If I have what I think is a crazy but great new idea, I have to test it, but even more important, others have to test it too and verify my findings. There is no “maverick” science, as ultimately, ideas must be tested in the wider community to be legitimized.

Mavericks have made interesting discoveries, but never in a vacuum. The Galileos of history worked in context, and they were not brilliant because of their “maverick-ness”, but because they were right.

So, moving on to their latest “hypothesis”

Autism spectrum disorders are complicated and multifactorial. We don’t know much about cause. We do know, by epidemiologic studies that autism and vaccines are not causally associated. We also have no reason to suspect an infectious agent or, say, aliens.

But that doesn’t stop a maverick.

A recent issue of Medical Hypotheses includes an article that tries to link autism to Lyme disease. Why pick those two diseases? Who knows. Perhaps because both attract a lot of cult medicine.

So let’s examine this “hypothesis”.

The paper doesn’t start well, as it begs the question immediately. For example, it simply assumes there is an autism “epidemic” that is “spreading” while evidence has shown this epidemic to be largely artifact. They also note that “[a]n association between Lyme disease (LYD) and other tick-borne infections (TBI) during fetal development and in infancy with autism, autism spectrum disorders (ASD) and autistic symptoms has been noted by numerous clinicians and parents.” I’m not sure what that means. If they are going to base a whole paper on a particular assertion/observation, they probably should cite some data. Just sayin’.

In the introduction, they also make a rather odd statement:

Since environment changes faster than genes, the rapidly emerging epidemic and geographical spread of ASD suggests significant environmental contributors, that may include infections.

W. T. F. First, is there a “geographic spread” of ASD? OK, let’s just assume there is (after all, the authors did). If there is, does this geographic distribution match the distribution of Lyme infections? For instance, is ASD more common in New England and Long Island, where Lyme is endemic? Is it less common in the Southwest, where Lyme is vanishingly rare? Their odd statement about genes and environment is not some grand discovery. Finding environmental factors through epidemiologic studies is pretty, well, standard. I wonder if they did that? I wonder if they even read the extant literature? Apparently, their “epidemiology” was limited to directly comparing incidence of autism and of Lyme disease on a state by state basis, without clear definitions or the use of standard statistics. Here is their blindingly stupid observation:

In a geostatistical review of CDC and IDEA statistics 10 out of the top 15 states overlap for the incidence of autism and LYD (MN, ME, MA, MD, CT, WI, RI, NJ, PA, VA).

The science of statistical analysis was developed to do away with this type of primitive observation.

It’s difficult to overstate how bad this paper is. First, it relies on the journal’s stated preference for maverick (i.e. way the hell out there) ideas. It starts with a hypothesis whose implausibility
matched only by it’s weak observational foundation. It then goes on to support this hypothesis with case reports and other weak “evidence”.

Ideally, an unusual hypothesis like this serves to inspire work on a new idea (contrary to the “maverick theory”). For this to happen, the hypothesis must be based on a plausible idea (it will have to stand up to a Bayesian analysis at some point). This paper is not such a jumping-off point, unless you are jumping off a cliff into a pool of fantasy.

Medical Hypotheses is truly the journal where one can “just make shit up.”

References

Robert C. Bransfield, Jeffrey S. Wulfman, William T. Harvey,
Anju I. Usman. The association between tick-borne infections,
Lyme borreliosis and autism spectrum disorders. Medical Hypotheses (2008) 70, 967-974.

Comments

  1. #1 metabopharm
    July 3, 2008

    I have to defend Medical Hypotheses! You can’t just “make [stuff] up” you need legitamate references to the scientific literature in your bibliography, at least.

    A singificant number of the hypotheses have been made by real scientists and have stimulated testing of the hypotheses. This is the function of the journal.

    I won’t deny that there is a certain amount of “woo” that appears in its pages, but Medical Hypotheses is a legitamate scientific journal with a specific and important purpose.

    I have never published in Medical Hypotheses, although I have considered it.

  2. #2 Chuck
    July 3, 2008

    “We do know, by epidemiologic studies that autism and vaccines are not causally associated.”

    What we do know is that genetics studies have not reached the scientific threshold of causation for a majority of ASD individuals. Ingredients in vaccines have not reached the scientific threshold of causation for a majority of ASD individuals. Environmental factors also have not reached the scientific threshold of causation for a majority of ASD individuals.

    Please provide a study that defines “causally association” and disproves a “causally association” with anything associated with ASD.

  3. #3 minimalist
    July 3, 2008

    Yeah no, I’m sorry metabopharm, Medical Hypotheses is pretty useless even outside of the genuine woo. I had a poke around the journal, looking at hypotheses relating to my area of expertise (lipids).

    One hypothesis in the same issue, regarding lipid rafts, jumped out at me because it’s such a severely abused concept in cell biology. Basically, for a few years after the pioneering work by Simons/Ikonen/van Meer work at the turn of the ’00s, you couldn’t go ten feet at a meeting without running into a poster where some rinkydink research group claimed to have identified a “lipid raft component” just because it was insoluble in Triton (which is only ONE potential sign of a raft component, if such things even really exist, and probably the least reliable one there is). If you believed everyone, then roughly 50% of all TM proteins were components of lipid rafts, and the rafts were roughly 50% of the surface are of an ENTIRE CELL. (Seriously, that was one calculation I saw published, in all seriousness, in a very high profile journal. Does nobody check math anymore?)

    Anyway, sloppy work about such a tenuous and bandwagon-y concept offends me deeply, and I wasn’t disappointed. The hypothesis, while not a bad one, offers absolutely no reason to think that the defect is in the organization of lipid rafts over any other potential defect, such as expression of some other component that interacts with HLA-G. There is no compelling bit of evidence that makes raft formation any more reasonable than any number of hypotheses I can or can’t conceive.

    Overall that paper seems emblematic of a lot of these hypotheses: it all seems straightforward enough so why aren’t you testing it? It’s nothing that overturns paradigms or changes one’s way of thinking about a problem: it’s a simplistic hypothesis that can be fairly easily tested. It’s something I might give to a grad student on rotation to try out.

    Even if it were an ironclad, well-supported hypothesis, it still doesn’t fit the grandiose vision the journal’s editor apparently has of “visionaries” and earth-shakers. It’s no wonder the journal gravitates toward woo; otherwise it’d just consist of useless who-cares kind of stuff like this, to pad out a researcher’s list of publications.

  4. #4 _Arthur
    July 3, 2008

    May I observe that there are a lot of urban babies, who have no known window of exposure to ticks. Oh, I see they included prenatal in the womb infection, for good measure.

    Also lacking from the paper is any data on autistic babies showing either trace of LYD infections proper, or the corresponding antibodies.

    There are also any number of babies who were bitten by ticks, had the tell-tale bullseye mark of LYD, and didn’t become autistic. So the causality would be weak at best.

  5. #5 katie
    July 3, 2008

    Heh…I teach pre-med students like this all the time. They all think they’re geniuses, so they feel like they don’t have to bother with the grunt work. And, universally, they all suck at stats. Top it off with their weird ideas about only people who failed at getting into med school go to grad school, and it’s all I can do not to give them a little pat on the head.

  6. #6 Eric Lund
    July 3, 2008

    You can’t just “make [stuff] up” you need legitamate references to the scientific literature in your bibliography, at least.

    We expand upon the hypothesis of Mende et al.[1] that there is a causal relationship between these conditions…

    [1]S. B. Mende et al., J. Geophys. Res. 108, 1344.

    There, that was easy: I referenced a legitimate scientific paper. Of course, as you might guess from the journal name, the paper in question has nothing to do with any biomedical field (nor do I; the paper is related to some of the research I’m actually doing). Somebody who actually has some passing familiarity with biomedical research could do a better job than I just did. Unless (1) the paper is refereed (2) by one or more referees who are actually paying attention, it’s all too easy to slip something of this kind into the literature. I will make a WAG that Medical Hypotheses is not a refereed journal–my guess is that it is on a par with Physics Essays, a favorite non-refereed dumping ground for crank theories on general relativity and other physics-type topics. There is one important difference: Following the advice of an article in Physics Essays is unlikely to kill or injure somebody.

  7. #7 Brian
    July 3, 2008

    There is, however, in the correspondence section, a very interesting hypothetical treatment for congestion..

  8. #8 Chris Noble
    July 3, 2008

    I have to defend Medical Hypotheses! You can’t just “make [stuff] up” you need legitamate references to the scientific literature in your bibliography, at least.

    Pseudoscience by definition involves all the superficial features of science but without the underlying basis. The whole point is to cover up the fact that you are making shit up.

    Pseudoscientific articles typically have hundreds of references. It is highly unlikely that anyone is going to actually read all 232 references that you stick on the end of your article.

    Pseudoscientists often adopt the scientificy habit of writing in the passive voice. “It has been shown …”, “It is widely accepted…” etc. This obfuscates the fact that they are just making up shit.

    A few years ago I also defended the role of Medical Hypotheses. Somebody challenged me to come up with a single article from the journal that has made a positive contribution to science. I cahnged my mind.

  9. #9 BGC
    July 4, 2008

    I am the editor of Medical Hypotheses, and delighted to observe that the journal is still capable of provoking such ‘strong’ reactions!

    I sometimes worry we are getting too dull, with a respectable impact factor of 1.276; c. 45000 downloads per month and an editorial advisory board including the likes of Arvid Carlsson, Sir Roy Calne and Antonio Damasio.

    And yes, the journal explicitly uses editorial review, not peer review.

    Vive la difference!

  10. #11 minimalist
    July 4, 2008

    Yeah wow; remove any sort of quality control or scientific rigor and you, too, can see the impact factor of your general-interest medical journal ‘soar’ to levels comparable to regional and/or highly-specialized journals.

    But hey, as long as you’re ‘comfortable’ where you are and have no desire to improve your standing, do as you like. Most people in fast-changing, cutting-edge fields tend to see that as death, though, and for good reason.

  11. #12 Snout
    July 4, 2008

    Wow, Brian, I just clicked that link about the nasal congestion treatment. It has brightened my day immeasurably.

    Is there an equivalent to Poe’s Law that applies to medical discourse?

  12. #13 HCN
    July 5, 2008

    Well, there is Scopie’s Law, but it refers to a specific website:
    http://rationalwiki.com/wiki/Scopie%27s_Law

  13. #14 Chris Noble
    July 5, 2008

    I am the editor of Medical Hypotheses, and delighted to observe that the journal is still capable of provoking such ‘strong’ reactions!

    Wouldn’t a better measure of a journal’s success be its contribution to science?

    Which articles in Medical Hypotheses have made a positive contribution?

  14. #15 Joe
    July 7, 2008

    “Which articles in Medical Hypotheses have made a positive contribution?”

    Autism: A novel form of mercury poisoning. Bernard S, Enayati A, Redwood L, Roger H, Binstock T 2001. Med. Hypotheses 56:462-471.

    This paper, with 184 scientific references, compared hundreds of similar symptoms of autism and mercury poisoning. Without this paper we would not have known that the cause of the current autism epidemic in children is ethylmercury.

  15. #16 HCN
    July 7, 2008

    Except, Joe, that the cause of autism is NOT ethylmercury. Where have you been? That canard has been disproved over and over and over again during the last few years. See:
    http://www.immunizationinfo.org/immunization_science.cfm?cat=1

    Note that since the removal of thimerosal from vaccines by 2001, that the rate of autism has not decreases. Even Generation Rescue has moved that goal post (see http://leftbrainrightbrain.co.uk/?p=428 for a timeline of those goal posts being metaforically pulled away, and up into the stadium grandstands).

    Now, if you have any studies that actually confirm that hypothesis (not paid by lawyers, or written by the Geiers), you might have something. Just show us what those papers are in the peer reviewed literature.

  16. #17 Joe
    July 7, 2008

    HCN, Here’s a link to the paper.

    http://www.autism.com/triggers/vaccine/mercury.htm

    Go there, get copies of the 184 referenced, published, peer-reviewed papers cited, and start reading. Get back to me when you are done.

  17. #18 Chuck
    July 7, 2008

    Ethylmercury has not been proven to be the cause for the majority of ASD individuals. Genetics also has not been proven to be the cause for the majority of ASD individuals. ASD was misdiagnosed under DSM and continues to be misdiagnosed under DSM IV. There is no scientific way to determine how many people are currently on the define spectrum. So what exactly does science really know about ASD HCN?

  18. #19 Joe
    July 7, 2008

    Have you guys read this article? It’s called “Dissecting a thimerosal study”. It really exposes all your dirty little tricks.

    http://www.naturalnews.com/022237.html

  19. #20 HCN
    July 7, 2008

    Joe, I asked for a peer reviewed confirmation of that that particular paper that was written in a NON-peer reviewed journal (read the blog entry above, see that Medical Hypotheses is not peer reviewed).

    Try to read and understand the information presented in front of you. Look up what the word “hypothesis” means (it might help you understand more about the journal “Medical Hypotheses”).

    Basically, the paper you claim is “proof” that ethyl-mercury causes autism was written by a bunch of people who have absolutely no medical expertise in heavy metal poisoning. The authors included a nurse, a chemical engineer, a guy with a Master’s in Business Administration (who later got fired from his paying job), and some other folks (including one or two connected with a ambulance chasing law firm).

    Now, it has been several years since that paper has been written… and there does not seem to be any actual data to back it up, and lots of studies to disprove it (note I included some links).

    If you have links to the peer reviewed literature that confirmed that paper you might have something. But that does not seem to forthcoming. Those papers seem to be hiding in the same spot that the studies replicating Wakefield’s lawyer funded paper on the MMR vaccine.

    In the mean time, lots of time, energy and money has been going after this stupid goose chase, with the goal posts being moved and moved. Then they also decided to lump in the MMR vaccine (which never contained thimerosal). Which in turn has caused outbreaks in pertussis, measles and mumps in recent years with death and disability following (about a dozen babies a year die from pertussis in the USA, there has been at least two teenagers who have died from measles in the UK in the past few year, plus many disabled, and in the American Midwest an outbreak of mumps in 2006 caused at least four people to become deaf). If you have other peer reviewed paper detailing how the DTaP is more dangerous than pertussis, diphtheria and tetanus… please tell us. If you also have a peer reviewed paper telling us how the MMR is more dangerous than mumps, measles and rubella… share that with us. The same goes for the IPV versus polio, and the Hib versus haemophilus influenza Type B… just let us know how big and bad those vaccines are versus the actual diseases.

    By the way, neither “autism.com” nor “Naturalnews.com” are peer reviewed journals. At a minimum they should be indexed at PubMed (which even indexes the NON-peer reviewed Medical Hypotheses).

    More information:
    http://www.nimh.nih.gov/health/publications/autism/complete-publication.shtml#pub6

  20. #21 HCN
    July 7, 2008

    An example of the type of paper that would be worthwhile:
    http://www.ncbi.nlm.nih.gov/pubmed/18180424?

    Discussed here:
    http://www.sciencebasedmedicine.org/?p=14

  21. #22 Chris Noble
    July 8, 2008

    “Which articles in Medical Hypotheses have made a positive contribution?”

    Autism: A novel form of mercury poisoning. Bernard S, Enayati A, Redwood L, Roger H, Binstock T 2001. Med. Hypotheses 56:462-471.

    This paper, with 184 scientific references, compared hundreds of similar symptoms of autism and mercury poisoning. Without this paper we would not have known that the cause of the current autism epidemic in children is ethylmercury.

    This just confirms my supicions.

    The main contribution of Medical Hypotheses is to provide a platform for pseudoscientists to reach a conspiracy-minded anti-science audience. Bravo! But it had 184 references – it must be scientific!

    I was after a paper published in Medical Hypotheses that was recognised by the scientific community and lead to more research published in peer-reviewed journals.

  22. #23 minimalist
    July 8, 2008

    I was after a paper published in Medical Hypotheses that was recognised by the scientific community and lead to more research published in peer-reviewed journals.

    I’ve no doubt that some of the publications in Medical Hypotheses were followed up by actual work… but most likely by the same lab group. But I take your point. I’d be deeply surprised if any paper there had been taken up by other groups and genuinely sparked new directions in research. Where I work, it’s treated as a joke by those who have even heard of it.

    I stand by my assessment: where Medical Hypotheses isn’t publishing outright crankery, it’s primarily a platform for researchers to pad out their list of publications. They get to double their productivity! One paper that says “we’re gonna do this”, and another that says “ok we did it”. Who, struggling for ever-more-scarce grant money, wouldn’t find that tempting?

    The reality of scientific research is precisely the opposite of the chief editor’s grandiose claims: the most productive, innovative labs that are challenging frontiers and spearheading new research do not feel the need to announce ahead of time that “we’re gonna do this”: they do it. Publishing it as a hypothesis is a waste of valuable lab time, especially if the results don’t pan out (as tends to happen with the vast majority of hypotheses).

  23. #24 Joe
    July 8, 2008

    For starters, Wakefield’s paper was submitted to Lancet long before any money from the legal fund was available to him. You need to check your facts and not just repeat the same tired talking points. His trial started in July 2007. If he’s so guilty what’s taking so long to convict him? Also, as someone who survived (easily) measles, mumps and chickenpox, you’re barking up the wrong tree. I’ll enjoy my lifetime immunity. Here’s some indexed, peer reviewed papers from Pubmed for you to read. See if you can put one plus one together.

    Vargus DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo Ca. 2005 Neuroglial activation and neuroinflamation in the brain of patients with autism. Annals of Neurology 57:67-81.

    Charleston J, Body R, Bolender R, Mottet N, Vahter M, Burbacher T 1996. Changes in the number of astrocytes and microglia in the thalamus of the monkey Macaca fascicularis following long-term subclinical methylmercury exposure. Neurotoxicology 17:127-138 (note: the paper explains that organic mercury, converted to inorganic mercury in the brain, leads to degenerative neuoinflammatory disease)

    Burbacher T, Shen D, Liberato N, Grant K, Cernichiari E, Clarkson T. 2005. Comparison of blood and brain mercury levels in infant monkeys exposed to methylmercury or vaccines containing thimerosal. Environmental Health Perspectives. 113:1015-1021 (note; the paper shows that thimerosal leaves behind twice as much inorganic mercury in the brain as compared to equal doses of methylmercury)

    Petrik MS, Wong MC, Tabata RC, Garry RF, Shaw CA. Aluminum [vaccine] adjuvant linked to gulf war illness induces motor neuron death in mice. Neuromolecular Med. 2007;9(1):83-100. (note: on a dosing per body weight basis, children recieve more aluminum than what’s been linked to neuron death and Gulf war disease)

  24. #25 HCN
    July 8, 2008

    Joe said “For starters, Wakefield’s paper was submitted to Lancet long before any money from the legal fund was available to him. You need to check your facts and not just repeat the same tired talking points.”

    Actually, it was only after the paper was published that the legal money was found out about. He failed to declare the competing interest, and most of the authors of that paper withdrew. Summary here:
    http://briandeer.com/mmr/lancet-summary.htm

    I repeat the same “talking points” because you seem to have trouble reading the information.

    Also, if you wander over to Respectful Insolence, you will see a thank you note to Wakefield over the fact that measles is now endemic in the UK.

    Also, the Vargas paper is not about thimerosal (mercury), the Charleston paper is about METHYLmercury, the Burbacher paper does not prove thimerosal causes autism (it does show why the Charleston paper is not appropriate… basically there is a big difference between METHYLmercury and ethylmercury), and the Petrik paper is about aluminum. Aluminum is not in thimerosal, nor is it a heavy metal — though it has been known to be part of rubies, sapphires and pickles (alum).

    None of those counter the several epidemiological studies done in several countries that included several hundreds of thousands of children over the past ten years that show no casual link between vaccine and autism.

  25. #26 Joe
    July 8, 2008

    To be clear, somebody else has usurped my name. I think HCN knew that, I am not sure who else did.

  26. #27 Chris Noble
    July 8, 2008

    I’ve no doubt that some of the publications in Medical Hypotheses were followed up by actual work… but most likely by the same lab group. But I take your point. I’d be deeply surprised if any paper there had been taken up by other groups and genuinely sparked new directions in research. Where I work, it’s treated as a joke by those who have even heard of it.

    I would go so far as to suggest that if you have a good hypothesis then the worst thing you could do is to bury your daisy underneath two tons of horseshit in Medical Hypotheses.

  27. #28 HCN
    July 10, 2008

    I just re-found this commentary today. It is an analysis of the paper Joe claims “proves” thimerosal causes autism:
    http://pediatrics.aappublications.org/cgi/reprint/111/3/674.pdf

    It includes a table of symptoms of mercury poisoning versus autism, and how they are not quite alike.