Respectful Insolence

If there’s one thing that antivaccine activists share in common, it’s the passionate (and as yet unproven) belief that “something” out there in the environment caused the “autism epidemic.” Usually, that “something” thought to be vaccines, but with the utter failure of the vaccine-autism hypothesis to the point where it is considered soundly refuted, antivaccinationists have gotten a bit more—shall we say?—creative. Now it’s something in the environment. Sometimes it’s mercury, despite the utter lack of evidence that mercury in vaccines is even remotely linked to autism. Sometimes it’s mercury from coal-burning power plants. Sometimes it’s pollution, even from China. Other times it’s pollution from freeways. Other times, it’s pesticides, acetaminophen, and antidepressants. Needless to say—but I’m going to say it anyway—the enthusiasm of autism cranks for these various causation hypotheses vastly outweighs any evidence in support of them, which is usually either really weak or nonexistent.

Well, here we go again.

I tried. I really did. I tried to let this cup pass, but it kept popping up on my Facebook feed. I kept seeing it on Twitter. Finally, I just had to say, WTF? If I can’t beat ‘em, I’ll beat ‘em over the head with science. I’m referring, of course to the latest study making the rounds claiming to find a link between autism and…something, anything! This time around, it’s pesticides, and here’s the CNN report on a study finding a link between pesticides and autism:

Scientists have long hypothesized that chemicals found in our environment play a role in causing autism. Research published this week in Environmental Health Perspectives supports that theory, finding children whose mothers are exposed to agricultural pesticides during pregnancy may be at increased risk for autism spectrum disorders, or ASD.

Researchers at the University of California, Davis, looked at the medical records of 970 participants. They found pregnant women who lived within a mile of an area treated with three different types of pesticides were at a two-thirds higher risk of having a child with ASD or developmental delays. These pesticide-treated areas included parks, golf courses, pastures and roadsides.

Before I get to the study itself, I couldn’t resist clicking on the link in the CNN story, which leads to another CNN story from 2011, Scientists warn of chemical-autism link. It’s basically a story that looks at all sorts of dubious studies linking the dreaded “chemicals” to autism. Very unimpressive. But what about this study? It comes from UC-Davis and Irva Hertz-Picciotto’s group at the Medical Investigations of Neurodevelopmental Disorders (MIND) Institute and appears as an advance publication in Environmental Health Perspectives. Sadly, it’s a thin a gruel as can be, a study that shows, basically, not much at all, and that’s being generous. At best, it might serve as a hypothesis-generating study, because it sure doesn’t nail down any risk between pesticide exposure and autism. Or not. In any case, I’ve encountered Irva Hertz-Picciotto before over at my not-so-super-secret other blog, although I wasn’t the one who wrote about her. Steve Novella was, noting that she said in a press release about an earlier study:

It’s time to start looking for the environmental culprits responsible for the remarkable increase in the rate of autism in California.

So right away, you know there’s a bias. Of course, every scientist has biases; that doesn’t necessarily mean she’s wrong about this study. Actually, there are lots of other reasons to think she’s wrong, or at least that, as I like to say when reviewing a scientific paper, the data do not support the conclusions made.

Before you can understand this paper, you need to know what the CHARGE study is, because that’s the study from which these data were reported. The CHARGE study is a case-control study of autism spectrum disorder (ASD) developmental delay (DD), and typical development consisting of 970 subjects in California. A case-control study, as you recall, is an observational study in which two existing groups are compared on the basis of an attribute thought to be causal for the outcome of interest. They’re often used to identify factors that might contribute to a medical condition by comparing people who have that medical condition (the cases) with a matched group of people who do not have the condition (the control group). For instance, it was a case control study by Sir Richard Doll in 1947 that was among the first to find strong evidence that smoking was associated with lung cancer, which was found by comparing subjects with lung cancer to those without and finding that many more subjects with lung cancer smoked. Groups are supposed to chosen so that they are as similar as possible except for the condition studied.

In any case, the control group should come from the same population as the cases, and the numbers of cases and controls don’t have to be equal. In this particular case control study of ASD and DD, there were three groups, 486 with ASD, 168 with DD, and 316 typical. So overall, the numbers weren’t really that large. All of the subjects in this particular study lived in California, within the catchment area for the MIND institute, defined as within a two hour drive from Sacramento.

Investigators then took advantage of a law in California that mandates that commercial application of agricultural pesticides be reported to the California Department of Pesticide Regulation (CDPR), which makes data publically available in the form of the annual Pesticide Use Report (PUR). The authors describe:

As described by CDPR, the pesticide use report data includes “…pesticide applications to parks, golf courses, cemeteries, rangeland, pastures, and along roadside and railroad rights-of-way. In addition, all postharvest pesticide treatments of agricultural commodities must be reported along with all pesticide treatments in poultry and fish production as well as some livestock applications. The primary exceptions to the reporting requirements are home-and-garden use and most industrial and institutional uses.”(California Department of Pesticide Regulation 2014)

Basically, the authors examined how close the mothers of the subjects of the CHARGE study lived to areas treated with pesticides during pregnancy and, using a complicated statistical model that examined distances from subject homes and pesticide application and tried to find correlations between “exposure” to pesticides by the mother during pregnancy and ASD or DD. The scare quotes are intentional, because using that word is dubious in the extreme. In fact, I could go into the detailed methodology more, delving into some of the analyses carried out. I don’t understand them all (not being a statistician), but if there’s one thing I’ve learned reviewing grants it’s that I don’t necessarily have to understand the detailed statistics when I understand experimental design, and this experimental design does not produce data that justify the conclusions of the paper. I could talk about how the authors looked at all sorts of different pesticides of different chemical classes and toxicities. I could, but I won’t—much. The reason is that this study is so fatally flawed from its very inception that there’s really very little point. If the overall design of the study is rotten, then all the details in the world won’t fix that.

Here’s what I mean. What are the hypothesis and the underlying assumption of this study? The hypothesis being tested is simple: Pesticide exposure during pregnancy is a risk factor for the child developing ASD or DD. However simple the hypothesis is, the problem is the definition of “exposure.” Clearly, the underlying assumption behind the study is that if a mother lived within a certain distance of pesticide applications during her pregnancy, that constitutes “exposure” to pesticides. So, when the authors conclude that children with ASD were 60% more likely to have had mothers who lived during their pregnancy within 1.25 km of pesticide application (and were therefore “exposed”) compared to typical children (adjusted odds ratio = 1.60, 95% confidence interval 1.02 to 2.51) and that mothers of children with DD were 150% more likely to have been “exposed” (adjusted OR=2.48, 95% CI=1.04-5.91), there’s a huge assumption being made that isn’t justified anywhere in the text with actual…oh, you know…evidence. Also notice the confidence intervals. These are the best confidence intervals the authors could find looking at different types of pesticides and different “buffer zone” distances, and they still come very close to failing to be even statistically significant (notice how the 95% confidence intervals almost include 1.0). I’m also pretty darned close to certain that the differences found are not clinically significant. (The two are not the same thing.)

The sine qua non of a good study demonstrating an association between an environmental exposure and a condition requires the actual verification and quantification of the environmental exposure under study in the cases. Sometimes this involves measuring the actual levels of the chemicals in question, either in the research subjects (ideally) to document exposure or in the places where they live and work. For instance, for a smoker estimating exposure can be done in a number of ways, from surveys to measuring cotinine levels in the urine or blood to verify exposure to tobacco smoke. Just living close to places where pesticides were applied does not mean there was an exposure. It just doesn’t. Pesticide use in California is heavily regulated (witness the reports to the state that were made publicly available that allowed the investigators to do this study in the first place.) Chances are that the amount of pesticide that made it into the air was negligible. We don’t know for sure, but there’s little reason to suspect that there were significant pesticide exposures over such distances from standard applications. I know that saying so will probably cause antivaccine activists to try to call me a shill for Big Chemical, to go along with my supposedly being a Pharma Shill, but such is life.

Table 3 is particularly revealing (and you can see it for yourself), where the authors looked at different chemical classes, different distances, different time windows of exposure between pre-conception, first trimester, second trimester, and third trimester. There seems to be no consistent pattern, no rhyme or reason. For instance, for some of the time windows, the adjusted OR increases with increasing distance! The distance-effect relationships are not consistent. The numbers seem a bit more consistent for DD, but the numbers are so small that few of the relationships reach statistical significance, an effect, given the number of comparisons, that looks consistent with random variation; i.e., “noise.”

The discussion section of the paper spends a lot of time looking at in vitro and animal studies in such a way as to distract from the utter unconvincing nature of the research findings just reported. Perhaps the biggest howler is this paragraph:

Several limitations to this study were unavoidable in the exposure assessment, potentially producing misclassification. Primarily, our exposure estimation approach does not encompass all potential sources of exposure to each of these compounds: among them external non-agricultural sources (e.g. institutional use, such as around schools); residential indoor use; professional pesticide application in or around the home for gardening, landscaping or other pest control; as well as dietary sources (Morgan 2012). Other sources of potential error include errors in reporting to the Pesticide Use Report data base, the assumption of homogeneity of exposure within each buffer, and potential geo-coding errors. Seasonal variation and address changes mid-pregnancy were accounted for by assigning an address to each day instead of one address for the individual, but information on hours spent in the home or elsewhere was not available.

Funny how the authors neglected the biggest limitation of them all: That they haven’t demonstrated that their assumption that living within 1.5 km of a source of pesticide application means that there was significant pesticide exposure is valid. True, the authors characterize their study as “exploratory” and are cautious with their language in their paper (although, I would argue, not cautious enough), elsewhere they let their true freak flags fly. For instance, in SFGate:

“This study validates the results of earlier research that has reported associations between having a child with autism and prenatal exposure to agricultural chemicals in California,” said lead study author Janie F. Shelton, a UC Davis graduate student who now consults with the United Nations. “While we still must investigate whether certain sub-groups are more vulnerable to exposures to these compounds than others, the message is very clear: Women who are pregnant should take special care to avoid contact with agricultural chemicals whenever possible.”

I would agree that pregnant women shouldn’t be handling industrial strength pesticides, but if there’s evidence that living within a mile or so of areas where pesticides are applied during pregnancy will cause a woman’s child to develop autism, certainly neither Shelton nor Hertz-Piccioto has provided it, either in this paper or elsewhere. Sadly, that didn’t stop the press from dutifully responding to the press release from the MIND Institute as though this study were slam-dunk evidence that pesticide exposure during pregnancy causes autism. It’s not, not by a long shot. It barely qualifies as maybe hypothesis-generating evidence. Wait. Strike that. I don’t think it qualifies even as that.

Comments

  1. #1 Darwy
    Røde grøde...you know the drill
    June 25, 2014

    My biggest beef with the paper – they’re trying to tie exposure to “Big Ag” use of pesticides – but they’re ignoring the more pertinent exposure route – household use.

    The same classes of pesticides mentioned in this study are also the most commonly used around the house and garden. RAID, Ortho, etc.

    How can they possibly control for that confounding data when the database they used doesn’t include residential, industrial or institutional use of pesticides?

    The average gardener also doesn’t always follow the guidelines for pesticide application as rigorously as Big Ag, I know I’ve been guilty of making a stronger mix for application than is advised by the packaging – how many others do the same?

    I think home exposure would be more relevant than distance to Big Ag, because we spend more time in our yards during the summer (and after fresh applications of pesticides on the flower beds, grass, etc) – which would be higher exposure than any carryover from a farm a mile and a half down the road.

  2. #2 Helianthus
    June 25, 2014

    Also notice the confidence intervals.

    adjusted OR = 1.60, 95% CI 1.02-2.51;
    adjusted OR= 2.48, 95% CI 1.04-5.91

    Ah, yes. Flirting with 1, isn’t it?

    In other dubious article news, the retracted Séralini paper on the link between GMOs, glyphosate and tumors in rats has been republished.

    I like the answer from the Genetic Literacy project:: How not to repeat the Seralini GMO rat study.

  3. #3 Darwy
    Røde grøde...you know the drill
    June 25, 2014

    @Helianthus

    Yeah, I saw the CI intervals and their OR – color me unimpressed. As Orac said, they’re barely relevant – and given that they’re missing a HUGE chunk of HIGHLY relevant data, I’m more apt to dismiss them.

  4. #4 Too Old For This
    June 25, 2014

    Golf courses, pastures, and road sides? Doesn’t most of the California population live within the study range of a sprayed area? Who all could function as comparators?

  5. #5 Todd W.
    http://www.harpocratesspeaks.com
    June 25, 2014

    Supposing that their idea of Big Ag pesticide use is correct, wouldn’t that suggest that there would be higher rates of ASD and DD in rural farm areas than in cities?

    But, yeah, the confidence intervals are not particularly impressive. And that limitations paragraph basically saying, “Oh, and there’s all these confounding variables that mean our study is useless for drawing any sort of conclusions, including the one we’re making.”

  6. #6 Denice Walter
    June 25, 2014

    Dan Olmsted is right on the case.( @ AoA). His book was there first.

    Also the re-animation of Seralini’s paper caused PRN’s head honcho to declare that FINALLY progress is being made about GMOs.
    After he mispronounced Seralini’s first name.

  7. #7 Helianthus
    June 25, 2014

    After he mispronounced Seralini’s first name.

    Those wacky French and their unpronounceable names :-)

  8. #8 Mike
    June 25, 2014

    I am really curious how the buffer zones were chosen. Pesticides certainly do drift, but they mostly drift down wind or in the water supply. Setting up buffer zones in circles around the application site seems to be irrational.

    Why the large gradient and then such fine gradients. the first buffer is 1.25 km, then 1.5 and 1.75 km. Those numbers do not seem to be based on a valid reason and instead were possibly chosen aftewards as a way to find a correlation. It is pretty easy to take a dataset and then fiddle with the paremeters until you find a correlation to become significant.

  9. #9 Mephistopheles O'Brien
    June 25, 2014

    I am really curious how the buffer zones were chosen.

    At a guess, convenience for analysis. They were unable to measure actual exposure, prevailing breezes, flow of water, amount of pesticides in the air and soil, and so on, so they set up a series of concentric circles of (hopefully) arbitrary width. Alternatively they tried different sized regions until they found the ones that looked best in data.

    I recall one study that was widely reported that tried to show a link between leukemia electromagnetic fields – however, the proxy they used for field strength was distance from a high tension power line. They found an association for people who could see these lines from their houses, but further studies did not find that this actually predicted field strength to any particular accuracy.

  10. #10 LW
    June 25, 2014

    I have an alternative hypothesis that fits the study *including* the fact that the correlation has nothing to do with water flow or prevailing winds.

    Autism has a genetic component, hence women who have autistic children are more likely than average to have autistic traits themselves. People with autistic traits may be more comfortable living far from the madding crowd, i.e., in less populated areas, hence people with autistic traits will be found living near pastures, parks, and golf courses slightly more often than expected based on their percentage of the population — without regard to prevailing winds or water flow. Therefore autistic children will be slightly more likely to be born to women living near pastures, parks, and golf courses than to women living further away.

  11. #11 Sarah A
    June 25, 2014

    Granting that prenatal exposure to pesticides has a bit more prior plausibility than vaccines, if agricultural pesticides were a major cause of autism, wouldn’t rates be going down due to urbanization?

  12. #12 Julian Frost
    Gauteng East Rand
    June 25, 2014

    LW, that’s a surprisingly plausible hypothesis.

  13. #13 Denice Walter
    June 25, 2014

    I think that there’s data about autism rates being higher near highways but that may be confounded with another factor.

  14. #14 Eric H.
    June 25, 2014

    How much pesticide can get into the air? Not a lot, nanograms/cubic meter… Biofortified had a great post about that a few months ago.
    http://www.biofortified.org/2014/03/roundup-in-75-of-air-what-the-report-actually-says/

  15. #15 Krebiozen
    June 25, 2014

    If pesticides cause autism (or anything else) we would expect to see a high incidence among farmers and their families, who are exposed to orders of magnitude more than anyone else. I’m not sure about autism, but if anything farmers are healthier than the rest of us. That’s one reason I stopped worrying about pesticide residues on vegetables.

    Is there any information about autism in farming communities (preferably not the Amish, who have other confounding factors)?

  16. #16 Denice Walter
    June 25, 2014

    @ Krebiozen:

    We also have to be aware that more rural areas MAY have less services INCLUDING those which assess ASDs.
    SO that would mean that those kids may be living in a system like that of oh,,, I don’t know… the 1970s when there were “low” rates of ASDs.
    Or so they tell me.

  17. #17 Calli Arcale
    http://fractalwonder.wordpress.com
    June 25, 2014

    Encouragingly, when I saw this pop up on Yahoo News, the comments were largely sensible ones expressing substantial doubt about the findings. Many talked about confounders and things like that, but there was also a clear sentiment of suspicion merely on the basis of how many studies there have been linking autism to whatever random thing the scientists seemed to have a beef against. So even the non-skeptical are starting to smell a rat when yet another study comes out linking yet another thing to autism.

  18. #18 RobRN
    June 25, 2014

    Yes – I’ve noted an uptick in “Post hoc ergo propter hoc” anti-vax rhetoric lately about pesticides AND herbicides too. One blog entry I saw blamed her son’s autism on the neighbor’s occasional use of Round-Up in his yard!

  19. #19 Eric Lund
    June 25, 2014

    Denice @13: There is a link in the OP to a post by Orac’s friend on that study. The study found a correlation between autism prevalence and proximity to freeways, but not to major surface highways or arterial roads. That correlation, like the ones discussed here, was only marginally significant.

    The difference between freeways and surface routes is faster sustained speed on freeways–the study involved cases in Los Angeles, where most freeways have 65 MPH speed limits, while on surface routes speed limits of 30-40 MPH are more common, and surface traffic must sometimes stop for red lights. But I am not sure this difference is big enough to make living near a freeway significantly worse than living near a major surface highway, particularly in Los Angeles, which is notorious for having freeway traffic jams at all hours of the day.

  20. #20 Narad
    June 25, 2014

    We also have to be aware that more rural areas MAY have less services INCLUDING those which assess ASDs.

    Like this?

  21. #21 LW
    June 25, 2014

    If pesticides cause autism (or anything else) we would expect to see a high incidence among farmers and their families, who are exposed to orders of magnitude more than anyone else.

    Shouldn’t there also be a dose-response effect, so that autism would not only be more common but also be more severe in farm families? Severe autism would require less sophistcated medical services to detect, hence we should know if there were a high incidence of severe autism in farm families.

  22. #22 Calli Arcale
    http://fractalwonder.wordpress.com
    June 25, 2014

    Obligatory reference to XKCD about jellybean colors:

    http://xkcd.com/882/

  23. #23 TBruce
    June 25, 2014

    @Krebiozen:

    There are several studies evaluating health risks associated with farming. They include a high risk of fatal injuries and and increased risks of chronic respiratory diseases such as hypersensitivity pneumonitis, as well as higher rates of certain malignancies, such as leukemia and lymphoma. There is a reduced risk of cardiac disease.
    The studies have not identified an increased risk of autism in farming families.

  24. #24 Shay
    from the Illinois upland corn prairie
    June 25, 2014

    There is a reduced risk of cardiac disease

    Not the way the ones around here eat.

  25. #25 Denice Walter
    June 25, 2014

    @ Calli Arcale:

    It seems that you’ve been quoted @ AoA comments on Dan’s article.

    At any rate, what makes me smirk a bit about ‘toxin-phobia” is that the world ( esp the so-called western world) *used* to be much more polluted than it is now. Many laws were passed and clean-ups took place. a few examples:

    - clean-ups of rivers near large cities ( e.g. London, NY- I have a few close connections to these efforts)
    - laws about pesticide use/ bans on many of them
    - automotive fuels contained lead which was prohibited
    - industrial pollution was visually obvious
    - clean air initiatives
    - clean ups of dumps
    - laws about CFFs
    - laws about smoking in public

    I recall about 30 years ago a developmental psych prof related that she took a tour of the rainforest in Central America : she and her companions were doused with a powder that was unnamed but she imagined to be DDT- she was quite realistic and didn’t hallucinate that event.

    Anyone here ever play with mercury from a broken thermometer? We know why it was called ‘quicksilver’ firsthand.
    My mother always said never to wear white on a train trip or in the city.

    -btw- I’m younger than Dan, Dachel and a whole lot of others @ AoA.

  26. #26 Darwy
    Røde grøde...you know the drill
    June 25, 2014

    @Denice

    There’s actually a case report of a father and son who apparently mistook DDT powder for flour and used it to prepare their fish for eating.

    http://www.ncbi.nlm.nih.gov/pubmed/15362598?dopt=Abstract

    I haven’t bothered to get the full study, but I do have to wonder how much ‘flour’ they used as a breading for the fish (or how much fish they ate).

  27. #27 AdamG
    June 25, 2014

    I haven’t bothered to get the full study, but I do have to wonder how much ‘flour’ they used as a breading for the fish (or how much fish they ate).

    This is actually a really interesting case, thanks for the link! I have the full text, and while no exact amounts of fish consumed are given, the authors do state that the son ate the majority of the fish, and speculate that that’s why he experienced renal failure but not his father.

  28. #28 Darwy
    Røde grøde...you know the drill
    June 25, 2014

    @AdamG

    Yeah, I had to go get the study myself, too :D

    I do have to wonder – who the hell keeps DDT in a jar in their kitchen??

  29. #29 AdamG
    June 25, 2014

    Today in bizarre internet coincidences…googling ‘kitchen jar ddt’ leads you to this. It matches your avatar Darwy!

  30. #30 Darwy
    Røde grøde...you know the drill
    June 25, 2014

    @AdamG

    You Sir, have won the internet today.

  31. #31 Narad
    June 25, 2014

    It seems that you’ve been quoted @ AoA comments on Dan’s article.

    The searing irony of the Dachelbot’s “open letter” is a riot.

  32. #32 The Grouchybeast
    June 25, 2014

    @Darwy

    If you visit the old workshop at the Jewelery Quarter museum in Birmingham, you can see the jar of potassium cyanide that was kept on the same shelf as the jars of tea and coffee. The lady who made the tea was the same lady who did the electroplating, so she found it more convenient to keep them all in the same place…

  33. #33 herr doktor bimler
    June 25, 2014

    but if anything farmers are healthier than the rest of us

    They are just more ruthless at culling the runts of their litters.

  34. #34 Vasha
    Ithaca NY
    June 25, 2014

    That case is also a perfect example of why pestcides often have a colorful dye added to them. Since this happened in 2004, I wonder if the manufacturer of the DDT has started doing so?

    Preventive safety measures are the great topic of conversation in my town this week since the inadequate brakes of a truck apparently owned by a fly-by-night company, failed on one of our steep hills and caused it to kill someone and severely damage a historic building. Not the first such incident here either. So systemic fixes are on everybody’s mind: since we can’t make sure that every truck is properly maintained, what can we do to the road? Better signage to divert heavy vehicles off steep roads… Maybe a pull-off ramp… Or something

    There’s been a parallel development in all sorts of areas over the past couple of centuries, in things like traffic engineering, product safety, and public health: more and more is learned about how to build safety into the system, since individuals are fallible. The traffic dilemma I stated has a parallel in vaccines: since we can’t make sure that no person is ever infected, for instance by visiting an endemic area, what can we do on a poulation level to achieve herd immunity? It’s system thinking.

  35. #35 The Grouchybeast
    June 25, 2014

    Whoops. That ‘coffee’ was supposed to be a ‘sugar’.

  36. #36 Denice Walter
    June 25, 2014

    So what is it?

    Amnesia or outright deception aimed at youngster that would allow someone OLD ENOUGH to remember that more contaminated world to talk about how increased toxins caused the so-called autism/ chronic illness epidemic after 1980.

    I would guess that anyone over around age 50 in the UK or US ( John, Dan, Mark, Kim, Ann etc) would recall those days at least a little. Certainly RFK who advocates clean rivers.

  37. #37 Jenora Feuer
    June 25, 2014

    I would guess that anyone over around age 50 in the UK or US (…) would recall those days at least a little.

    I’m ‘only’ 46, and in Canada, but I certainly remember talk about acid rain resulting in damage to historic buildings. Granted, acid rain is still a problem: the real work on reducing that didn’t even start until the 1991 Canada-U.S. agreement. But it’s much less of a problem than it used to be.

    (The worry is whether it will stay that way, as parts of the U.S. are definitely looking at ‘clean’ coal to replace oil and gas in some power generation facilities, since the U.S. wouldn’t have to import as much…)

    There are several studies evaluating health risks associated with farming. [...] There is a reduced risk of cardiac disease.

    One has to wonder whether that’s because cardiac disease tends to be a late-in-life thing, and farmers are just more likely to die before getting that far.

  38. #38 Bob G
    Los Angeles
    June 25, 2014

    @10 LW

    It would appear that some cases of autism are linked to somatic mutations in, for example, the father’s sperm, which would not show up as familial inheritance from the parents or grandparents. Other cases seem to involve familial inheritance, and that’s where your hypothesis fits. However, there may be other conditions associated with at least a subset of the genes that result in autism, and one might be paranoia. I remember making this suggestion in this discussion group a few years ago. It fits with the small group of people who have autistic children (apparently of the severe variety) and come across as paranoid personalities. You know — everything is a conspiracy, nobody in authority can be trusted, and whole industries are in on the plot to make money by harming our children. It would also appear that most parents of the severely autistic are pretty normal (at least as normal as the rest of us) and deal with the stresses of child rearing as best they can, often to a heroic level.

    When I posted this, as I recall, I was attacked by a few people (mostly not posting anymore) for even suggesting such a thing as a link to parental oddities when you think about children who are not neurotypical.

    Of course the answers will eventually come when real data as to the genetic part of autism and various kinds of paranoia become known.

  39. #39 Bob G
    Los Angeles
    June 25, 2014

    @19 Eric Lund

    There is a substantial body of data that is fairly recent, mostly coming from the University of Southern California group that has been looking at air quality and various disorders. They have been looking at small particulate matter in the 2.5 micron range (pm 2.5) as well as in the 10 micron range (pm 10). They also now have some data on ultrafine particles (100 nm range). One finding is that abnormal lung development is correlated with distance from the freeway, in particular along the 710, which serves a huge volume of diesel trucks coming from the port. Diesel trucks are one of the more substantial emitters of particulate matter.

    The effects fall off pretty quickly with distance. If I recall, maybe a quarter of a mile is what it takes. Also, the ultrafine particles aggregate pretty fast, but you get a plume of them when you are following a diesel truck.

    The difference between the freeway and surface streets is likely the dose, and in particular, the dose coming from diesel trucks.

    There is a lot of urban mythology prevalent in the portside areas, because there are a lot of things to blame. A few years ago, it was petroleum coke. Now it is the trucks. Not long ago, the television news ran a story about a cancer cluster at an old firehouse that used to house a color film laboratory. The statistics didn’t really fit, but that didn’t stop the local tv station by running a faux expose.

  40. #40 Denice Walter
    June 25, 2014

    @ Bob G:

    It’s not unreasonable:
    Snitz et al (2006) reviewed cognitive deficits observed in UNAFFECTED first degree relatives of people with schizophrenia.
    While the two conditions are not the same, they are both genetic and affect executive functioning and other cognitive abilities. Although ASDs may involve *de novo* mutations.

    There’s also a possibility that ASDs may be related to other conditions that affect thought and emotion.

  41. #41 Glaxxon PharmaCOM Orbital
    On the Winning Team™!
    June 25, 2014

    MESSAGE BEGINS———————————-

    Shills and Minions and most especially, our esteemed Cybernetic Host,

    I do hope that the PharmaLucre™ has been satisfactory of late. If you are thinking about serving some other marauding species that shall go nameless (mostly because their language is akin to the clatter of trash droids falling down a metal gangway). I certainly understand the lure of the new and perhaps glamorous world of Chemicals, but we use chemicals in our endeavors. And such lovely chemicals, indeed. I mean, why do you think they call them “chemtrails?”

    Unhappy monkeys, please let Miss Flinders know if there are any grievances we might help you resolve as regards your service to The Glaxxon Empire. We value your participation ever so much, and certainly let us know if, for instance, some other Shill or Minion seems to be listless, nattering or unhappy. We want to help. And there might be a little extra in your courier satchel if the information results in a kil . . . I mean, a re-education of the underperforming agent.

    Looking forward to seeing you all at our annual Planetary Subjugation Phuntime Pharma Jamboree in Sedona. Those that survive the purges, that is.

    Lord Draconis Zeneca, VH7ihL
    Rear Grand Exhalted Mavoon of the Great Fleet, Order of the Amazon, Rug Master Class VXII

    Glaxxon PharmaCOM Orbital
    00101110101100001010101110101011111101010100101010101
    ———————————————–MESSAGE ENDS

  42. #42 Sid Offit
    June 25, 2014

    Amazing how much garbage is produced by “the science.” Too bad so much of it funded with stolen taxpayer money

  43. #43 Pareidolius
    June 25, 2014

    I was just thinking how few trolls there have been in these parts of late and then . . . a Derp-O-Gram from fire marshall Bob. Just like old times.

  44. #44 novalox
    Watching siddy boy bat way below the Mendoza line
    June 25, 2014

    @sid

    So that means you won’t be on the internet anymore? Since after all, it was started with “stolen taxpayer money.”

  45. #45 Narad
    June 25, 2014

    Too bad so much of it funded with stolen taxpayer money

    DARPA’s on line 2, Bob. They want their Internet back.

  46. #46 Sid Offit
    June 25, 2014

    Internet. My favorite leftist trope. Besides I thought it was ALGORE not DARPA I should thank. You put us 16 to 80 trillion dollars in debt and your biggest accomplishment is linking a few computers together. Astonishing. No one could have figured that out…ever.

    Additionally it would have remained an after thought were it not for a quasi free market in which it could flourish. And much of the internet arose in connection with national defense efforts many see as a justifiable government role. What’s next a tribute to Tang?

  47. #47 Ken
    June 26, 2014

    Speaking of internet coincidences, cracked.com[*] today has “4 Tiny Historical Changes That Made Modern Life Possible”. To save you looking it up, they chose putting iodine in salt, not putting lead in gasoline and paint, eradicating hookworm (alas not globally), and the Pure Food and Drug Act.

    [*] A humor site, but more scientifically accurate than other sites often mentioned here…

  48. #48 ann
    June 26, 2014

    What’s next a tribute to Tang?

    Roads.

  49. #49 ann
    June 26, 2014

    automotive fuels contained lead which was prohibited

    http://www.motherjones.com/environment/2013/01/lead-crime-link-gasoline

  50. #50 Narad
    June 26, 2014

    You put us 16 to 80 trillion dollars in debt and your biggest accomplishment is linking a few computers together. Astonishing. No one could have figured that out…ever.

    “You”? Are you talking into your pants again, Bob? I suppose you’re right, though: We could have had FidoNet!

    Speaking of things that no one can figure out, though, where again does one go to order those two imaginary child-rearing books that you’ve been telling people about?

  51. #51 novalox
    June 26, 2014

    @sid

    Again, since you complain about “stolen tax money” so much, you should stop using the internet and suspend all of your facebook accounts, since they were all supported by that evil government.

    Of course you won’t which just proves how much of a hypocrite you are. Which of course, still ranks below your comments to a mother whose child died of the flu that it was “just the flu”

  52. #52 Narad
    June 26, 2014

    Additionally it would have remained an after thought were it not for a quasi free market in which it could flourish Eternal September.

    FTFY. But anyway, speaking of the Wisdom Of The Market, your blog seems awfully deserted, Bob. Have you given up in favor of just bumming FB space to try to run a crappy aggregator?

  53. #53 Narad
    June 26, 2014

    Oh, and be sure to check back to update everyone on the non-governmentally-supported college you’re going to be paying cash on the barrelhead to send your daughter to.

  54. #54 Helianthus
    June 26, 2014

    your biggest accomplishment is linking a few computers together. Astonishing. No one could have figured that out…ever.

    Bob, a.k.a. Sid “Offit”. Belittling others people’s achievements since he hit 12.
    “Sure, you did your job, but I could have done it too, no sweat.”

  55. #55 Krebiozen
    June 26, 2014

    TBruce,

    There are several studies evaluating health risks associated with farming. [...] There is a reduced risk of cardiac disease.

    And Jenora,

    One has to wonder whether that’s because cardiac disease tends to be a late-in-life thing, and farmers are just more likely to die before getting that far.

    I don’t think so, despite accidents, according to the CDC:

    In 2010, 476 farmers and farm workers died from a work-related injury, resulting in a fatality rate of 26.1 deaths per 100,000 workers. Tractor overturns were the leading cause of death for these farmers and farm workers.

    That’s lower than the death rate from accidents in the general population:

    All unintentional injury deaths
    Number of deaths: 120,859
    Deaths per 100,000 population: 39.1
    Cause of death rank: 5

    Obviously farmers are subject to all the other causes of death as well, but I think this shows that most farmers don’t die from accidents instead of cardiac disease.

  56. #56 Krebiozen
    June 26, 2014

    Continuing in a separate comment to avoid moderation.
    Also, according to cancer.gov:

    Farmers in many countries, including the United States, have lower overall death rates and cancer rates than the general population. Lower death rates among farmers for heart disease and cancers of the lung, esophagus, bladder, and colon, in particular, are thought to be due, at least in part, to lower smoking rates, as well as more physically active lifestyles and dietary factors.

    My reading suggests only a small increase in risk of leukemias and lymphomas in farmers, for example this meta-analysis found a barely statistically significant and only slightly increased risk of NHL but only in male farmers. This review found a statistically insignificant association between myeloid leukemias and occupational pesticide exposure, with a significant association in subgroups such as manufacturing workers and pesticide applicators. It isn’t an association I would be concerned about even if I were a farmer, and certainly not if I simply lived near a farm.

  57. […] Orac has already reviewed this study and I agree with his assessment – this conclusion is not justified by the data presented. […]

  58. #58 rork
    June 26, 2014

    I thought Novella a bit better, but also not good enough.
    I think their findings are “interesting” and hypothesis generating, but certainly not conclusive. My insolence returned:
    1) Odds ratios of 1.6 or 2.5 not clinically significant? Ask if you’d feel the same if it were odds of infectious disease from not vaxing or similar.
    2) Don’t need to get the stats cause I understand the design? Sounds anti-science. Also, some slavery to .05 being magical in hypothesis tests (CI close to 1).
    3) Failure to note all point estimates in table 3 are >1, but calls the pattern inconsistent, just noise.
    4) Trying to disparage location as a useful proxy in epidemiology – even though we are supposed to know about London, cholera, 1800s, and that the superhero John Snow is not the one from Game of Thrones. Snow (and others before him) put dots on maps. Yes, the better studies that followed actually ask people where they got their water rather than using just location, and finally removing the pump handle at the worst offending pump also helped as a followup, but stupid-old-locations was how the hypothesis was generated.
    On the other side I also have other criticisms of the paper (possible confounds, mentioned by several commenters), and the press releases were indeed terrible, trying to point to trends with distance when those weren’t demonstrated to be significant. Not even tested I think. Abstract and results mention differences as if they were significant when they aren’t (and they fail to note that). How dare they, and how dare reviewers permit that.

  59. #59 Orac
    June 26, 2014

    Odds ratios of 1.6 or 2.5 not clinically significant?

    In this particular study, yes, given the marginal statistical significance of some of the findings, the data dredging that appears to be going on here, and the lack of a consistent distance (dose)-response effect or timing effects consistent with the known mechanisms of action of the various pesticide classes, the point being that statistically significant doesn’t necessarily mean clinically significant. When you get an aOR of that size with such huge confidence intervals, then, going on the basis of one study, it’s hard to ascribe much clinical significance to it unless more convincing data are found.

    Don’t need to get the stats cause I understand the design? Sounds anti-science.

    Not at all. If the “big picture” design isn’t sound, then the stats rarely matter much. Sorry, but they don’t. If the design is irredeemably screwed up from the beginning, then it doesn’t really matter if the stats were done properly. Looking at the “big picture” of the experimental design always comes first. That’s what my statisticians where I work keep telling me.

    Failure to note all point estimates in table 3 are >1, but calls the pattern inconsistent, just noise.

    By “inconsistent,” I meant that there’s no consistent distance-response effect noted, as I pointed out in the post. That is a finding that would be very important to validate a model in which proximity is used as a proxy for exposure, and it’s not there. For some of the point estimates, I noted that the aOR actually increases with distance.

    Trying to disparage location as a useful proxy in epidemiology – even though we are supposed to know about London, cholera, 1800s, and that the superhero John Snow is not the one from Game of Thrones. Snow (and others before him) put dots on maps. Yes, the better studies that followed actually ask people where they got their water rather than using just location, and finally removing the pump handle at the worst offending pump also helped as a followup, but stupid-old-locations was how the hypothesis was generated.

    The “superhero” John Snow started out with the clusters and then figured out that they were near water pumps. Since it was known that the people living in that area got their water from those pumps, the assumption of exposure to “something” in the water causing the disease was not nearly as tenuous because Snow knew the people in the area drank the water. In marked contrast, our intrepid pesticide investigators have done nothing to show that people who live within their distances of the various sights of pesticide application. So as a hypothesis-generating exercise, maybe it has marginal value, but based on this study I sure wouldn’t recommend spending a million dollars to do a more proper followup, perhaps a prospective study with measurements of actual pesticide levels in the homes and maybe some blood and urine samples to verify exposure (and that’s a lowball estimate of what it would likely cost).

    I will take my lumps for not discussing all the confounders, but I chose to focus on what I considered to be the main flaw. All those other confounders are just icing on the cake of the argument that this paper is a piece of crap.

  60. #60 Lawrence
    June 26, 2014

    Given the current research shows that “pesticides” don’t travel very far (certainly not the width of even a single state), I find it funny that AoA is trying to blame pesticide use in California for the “higher” rate of autism in New Jersey – simply because New Jersey is East of California…..

  61. #61 Todd W.
    http://www.harpocratesspeaks.com
    June 26, 2014

    @rork

    2) Don’t need to get the stats cause I understand the design? Sounds anti-science. Also, some slavery to .05 being magical in hypothesis tests (CI close to 1).

    I don’t need to look at the stats of a homeopathy or reiki paper if the design is crap. Looking at the stats section would largely be good for figuring out whether they used the proper statistical tests, but more important is, as Orac says, the design and big picture view of what’s going on in the study.

  62. #62 rork
    June 26, 2014

    @59 I was not criticizing our author for not discussing confounds. No lumps intended, there anyway.

  63. #63 rork
    June 26, 2014

    @59 just one repeat:
    “For some of the point estimates, I noted that the aOR actually increases with distance.”
    I know. Those differences are not significant though, and we can expect that for a study this small (we are sampling) and distances so similar. That they were all positive and did not vary more than I’d expect was the overlooked part.

  64. #64 herr doktor bimler
    June 26, 2014

    the press releases were indeed terrible, trying to point to trends with distance when those weren’t demonstrated to be significant. Not even tested I think.

    I suspect that writing the press releases was the first step, before conducting the study.

  65. #65 LW
    June 26, 2014

    Speaking of confounds, do they apply pesticides year-round in California? They don’t around here. Would that not suggest a hypothesis that autistic children are more likely to be born in some seasons than others in the vicinity of pastures, parks, and golf courses? If not, why not?

  66. #66 Stuartg
    June 27, 2014

    I wonder why they didn’t use 0.25, 0.5, 0.75 and 1.0 km buffer distances as well?

    If there was a real relationship then those buffer distances should have even higher incidence of ASD and DD.

    I suspect the buffer distances in the abstract were (cherry) picked for publication because shorter buffer distances did not show a relationship. (I don’t have access to the entire paper).

  67. #67 Krebiozen
    June 27, 2014

    I’ve been meaning to respond to rork’s mangling of the John Snow story:

    Trying to disparage location as a useful proxy in epidemiology – even though we are supposed to know about London, cholera, 1800s, and that the superhero John Snow is not the one from Game of Thrones. Snow (and others before him) put dots on maps. Yes, the better studies that followed actually ask people where they got their water rather than using just location, and finally removing the pump handle at the worst offending pump also helped as a followup, but stupid-old-locations was how the hypothesis was generated.

    As a matter of fact Snow proposed his hypothesis in 1849, five years before the Broad Street cholera outbreak. You can follow his reasoning in his paper, ‘On the Mode of Communication of Cholera’. That the disease was communicable was undeniable, he argued; if it were air-borne more people would succumb, the first symptoms are associated with the alimentary canal so it is most likely ingested, and later excreted in the copious diarrhea the disease produces. Snow was already convinced that cholera was water-borne years before the Broad Street outbreak.

    Looking at Snow’s account of his investigation, we see the first thing Snow did on investigating the outbreak was to look at the location of the cases relative to local water sources, and to talk to affected families, asking where they got their water. This quickly revealed the Broad Street pump as the likely culprit, and was sufficient evidence to convince the Council to remove the pump handle. The map with the dots (“stupid old location” as rork characterizes it), and the statistics, came later, after the hypothesis had been confirmed empirically.

    Incidentally, that particular outbreak had probably burned itself out – the Reverend Henry Whitehead identified the likely source, a young girl with typhoid who used a cesspit right next to the pump, and an engineer confirmed fecal leakage into the pump well. However, the girl’s father later contracted cholera and had the pump still been in use, would undoubtedly have started another outbreak.

  68. #68 rork
    June 27, 2014

    By 1849 cholera had visited many times before.
    “History of the Cholera in Exeter in 1832″. Shapter.

  69. #69 rork
    June 27, 2014

    I’m suggesting geographic patterns may have helped suggest the hypothesis long before 1849, how much so, I’m not certain. I want to add that there is famous peril in coming into geographic analysis with your priors not very settled. My mentor testified in court cases about leukemia clustering in West Cumbria, cause he was a radiation effects expert: http://www.ncbi.nlm.nih.gov/pubmed/10331534. There’s a famous graphic I can’t find now, showing how with dots here and there on a map, you will be able to come up with some spatial correlation to something (dumps, paper mills, nuclear power), even if the locations of the cases are in fact randomly distributed.

  70. #70 Krebiozen
    June 27, 2014

    I gave the wrong link for Snow’s 1849 treatise ‘On the Mode of Communication of Cholera’ above (I repeated the link to his writings on the Broad Street outbreak). The correct link is here (PDF).

    My point is that it was not “stupid old location” that generated Snow’s hypothesis, but his careful examination of contemporary knowledge of the disease. It wasn’ t his famous map that confirmed his hypothesis and convinced the Council to remove the pump handle, it was the fact that the majority of those that succumbed got their water from the Broad Street pump.

    I agree about clustering. We tend to forget that ‘random’ does not mean ‘evenly distributed’ and find patterns where none exist. If there was a link between pesticides and autism, I would expect to see results far more unequivocal than this study found; perhaps something like Snow’s results.

  71. #71 Krebiozen
    June 27, 2014

    By 1849 cholera had visited many times before.
    “History of the Cholera in Exeter in 1832″. Shapter.

    Of course, but Snow, in 1849, was one of the first to suggest it was transmitted via the fecal-oral route. Shapter clearly had no clue, as the people of Exeter spent great efforts fumigating, burning pitch, scattering lime and burning clothes, none of which would have been the least bit helpful. Shapter made a map of cases too, but it didn’t help him to figure out the etiology of the disease.

  72. #72 brewandferment
    June 27, 2014

    speaking of cholera, I recently read “The Dress Lodger” by Shari Holman, set in Sunderland, England in 1831. It’s pretty gruesome in spots but it mentions several of the cholera efforts described by Kreb #71. It also works in the afflictions of mercury-poisoned workers among other things. Bloodletting gets a mention, too. Worth a read but don’t say I didn’t warn you about grim content.

  73. […] Orac has already reviewed this study and I agree with his assessment – this conclusion is not justified by the data presented. […]

  74. […] little in the way of significant data. If you want a complete takedown of the article, check out Orac’s post on the blog Respectful Insolence, or Steven Novella’s post on the NeuroLogica blog. The long and short of it is that we […]

  75. […] Orac also did a review of this study, almost for the same reasons as I did–here comes ANOTHER cause of autism. His review of the data lead him to this observation: […]