MMR-autism link is clearly “busted”

Over at Aetiology, Jan Helldén mentioned a study:

“I would like to point everyone who believes that there is a connection between autism and vaccination to a Danish study that includes almost one tenth of the population. It was published in The New England Journal of Medicine in 2002 (KM Madsen, et al.: A Population-Based Study of Measles, Mumps, and Rubella Vaccination and Autism, NEMJ Vol. 347:1477-1482, No. 19). The abstract says it all.”

ABSTRACT

Background:
It has been suggested that vaccination against measles, mumps, and rubella (MMR) is a cause of autism.

Methods:
We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998. The cohort was selected on the basis of data from the Danish Civil Registration System, which assigns a unique identification number to every live-born infant and new resident in Denmark. MMR-vaccination status was obtained from the Danish National Board of Health. Information on the children’s autism status was obtained from the Danish Psychiatric Central Register, which contains information on all diagnoses received by patients in psychiatric hospitals and outpatient clinics in Denmark. We obtained information on potential confounders from the Danish Medical Birth Registry, the National Hospital Registry, and Statistics Denmark.

Results:
Of the 537,303 children in the cohort (representing 2,129,864 person-years), 440,655 (82.0 percent) had received the MMR vaccine. We identified 316 children with a diagnosis of autistic disorder and 422 with a diagnosis of other autistic-spectrum disorders. After adjustment for potential confounders, the relative risk of autistic disorder in the group of vaccinated children, as compared with the unvaccinated group, was 0.92 (95 percent confidence interval, 0.68 to 1.24), and the relative risk of another autistic-spectrum disorder was 0.83 (95 percent confidence interval, 0.65 to 1.07). There was no association between the age at the time of vaccination, the time since vaccination, or the date of vaccination and the development of autistic disorder.

Conclusions:
This study provides strong evidence against the hypothesis that MMR vaccination causes autism.

If I read this correctly, a vaccinated child has a 17% lower chance of getting an autism-spectrum disorder and an 8% lower chance of developing autism than one that is not vaccinated. In other words, vaccination seems to protect against autism. Interesting!

Thanks for the reference!

Neuroskeptic: “fMRI gets slap in the face with a dead fish”

Neuroskeptic blog (“because brains are stupid”) has a nice commentary on the dead salmon brain-scan story.

fMRI of dead salmon: how not to do science

Uncorrected randomness leads to false positives

Craig Bennett at Prefontal blog had highlighted the problem of cherry-picking data to collect false positives. He did this in a memorable way by presenting a poster of fMRI scans of a dead fish: “Dead salmon responds to pictures of people.”

A dead salmon has become a scientific celebrity after its brain supposedly lit up when shown pictures of humans during a brain scan.

…the study was done to show that data from an fMRI brain scan can lead to false positives — misleading results — if not carefully analyzed.

Yes, the salmon was dead — bought in a lifeless state at a fish market and scanned an hour later. No, the results are not shocking or miraculous. Like many scientific studies, the study and its results, presented earlier this year in a poster at a conference, are technical and rather bland:

“The goal of the salmon poster was to encourage the minority of researchers who report uncorrected statistics to move forward and begin using basic multiple comparisons correction in their research,” says study leader Craig Bennett, a postdoctoral researcher in the Department of Psychology at the University of California, Santa Barbara.

In a nutshell, the data reported by Bennett and colleagues in no way suggests the salmon’s brain was functioning, but rather reveal anomalies that can be misleading if you’re not careful.

That, of course, is the statistical problem that plagues studies of everything from drug efficacy to ESP: it skews your data to keep positive results and throw away negative ones. Whatever corrections, processing, or reporting standards you use must be decided on in advance and applied to all results.

Follow-up: read “The story behind the Atlantic salmon.”

“Cargo cult science” by Richard Feynman

This was extracted from Richard Feynman’s address to a graduating class in 1974. Among other things, he points out that, if you don’t understand science, adopting its trappings will not make what you do magically become science. There’s a nice, clear copy here: “Cargo Cult Science.”

In the South Seas there is a cargo cult of people. During the war they saw airplanes with lots of good materials, and they want the same thing to happen now. So they’ve arranged to make things like runways, to put fires along the sides of the runways, to make a wooden hut for a man to sit in, with two wooden pieces on his head to headphones and bars of bamboo sticking out like antennas–he’s the controller–and they wait for the airplanes to land. They’re doing everything right. The form is perfect. It looks exactly the way it looked before. But it doesn’t work. No airplanes land. So I call these things cargo cult science, because they follow all the apparent precepts and forms of scientific investigation, but they’re missing something essential, because the planes don’t land. Now it behooves me, of course, to tell you what they’re missing. But it would be just about as difficult to explain to the South Sea islanders how they have to arrange things so that they get some wealth in their system. It is not something simple like telling them how to improve the shapes of the earphones. But there is one feature I notice that is generally missing in cargo cult science. That is the idea that we all hope you have learned in studying science in school–we never say explicitly what this is, but just hope that you catch on by all the examples of scientific investigation. It is interesting, therefore, to bring it out now and speak of it explicitly. It’s a kind of scientific integrity, a principle of scientific thought that corresponds to a kind of utter honesty–a kind of leaning over backwards. For example, if you’re doing an experiment, you should report everything that you think might make it invalid–not only what you think is right about it: other causes that could possibly explain your results; and things you thought of that you’ve eliminated by some other experiment, and how they worked–to make sure the other fellow can tell they have been eliminated.

Details that could throw doubt on your interpretation must be given, if you know them. You must do the best you can–if you know anything at all wrong, or possibly wrong–to explain it. If you make a theory, for example, and advertise it, or put it out, then you must also put down all the facts that disagree with it, as well as those that agree with it. There is also a more subtle problem. When you have put a lot of ideas together to make an elaborate theory, you want to make sure, when explaining what it fits, that those things it fits are not just the things that gave you the idea for the theory; but that the finished theory makes something else come out right, in addition.

In summary, the idea is to give all of the information to help others to judge the value of your contribution; not just the information that leads to judgement in one particular direction or another.
—Richard Feynman

Irreducible no more

It looks as if Nick Matzke’s hypothesis is correct, and the base of a bacterial flagellum was re-purposed from a structure used in the immune system. In fact, scientists are ready to recognize that the flagellum base plate is a variation of the type III secretion system. Nick wrote

Finally, if I were doing a revision, I would update the terminology along the lines suggested in Desvaux et al. 2006 (“Type III secretion: what’s in a name?” Trends in Microbiology 14(4), 157-160, April 2006 - DOI). As they point out, the terminological distinction between “flagellum” and “type 3 secretion system” is dubious and artificial, and it is more true to acknowledge that flagella have a type III secretion system. Therefore, there are two known groups of type III secretion systems, flagellar and nonflagellar, abbreviated F-T3SS and NF-T3SS.

There is much more to be said about recent research and its implications for flagellum evolution. For the near future I intend to post my thoughts on this in the new flagellum evolution section [UPDATE: fixed the link] of the Panda’s Thumb blog.