Saturday, December 15, 2012

Autism, empathy, and violence: One of these things doesn't belong here

Some news coverage in the last 24 hours has mentioned autism in the context of the tragedy in Connecticut, particularly referencing Aspergers or "high-functioning" autism. Talking heads have brought up the "empathy" factor when discussing autism, and I'd like to set some of the record on that straight.

Empathic ability comes in two forms. One is the social ability to recognize the emotion someone is feeling by following social cues, subtle vocal fluctuations, and other nonverbal communications. Psychopaths, for example, might be quite good at reading people, at applying this cognitive empathy and then possibly exploiting it. Autistic people, on the other hand, generally tend not to be that great at this kind of recognition in non-autistic people. After all, the hallmark of autism is difficulty navigating this territory and registering the meaning of a nonverbal language that is unfamiliar to them. Worth noting, non-autistic people also seem to struggle with reading the nonverbal communication of autistic people. It can also be difficult for autistic people to automatically place themselves situationally in the other person's shoes and intuit the emotion the other person feels, although again, non-autistic people seem to struggle to do this for autistics. Autism does not, however, preclude a person from understanding a clear communication about emotion.

The other form of empathy follows on the recognition of the emotion, whether the message comes through verbally or nonverbally, intuitively or not. That's the form in which you not only can intellectualize the person's emotion but also can internalize and feel what they are feeling, known as emotional empathy. The gap for psychopaths comes in here: They seem to lack this emotional empathy. But whatever deficits autism might carry in terms of recognition, it makes up for in terms of the shared feeling. My experience has been that once an autistic becomes aware of the other person's emotion, the feeling comes without a social construct, naked and in full, unmodulated. Certainly, the expression of their feeling can be more intense. Research shows that people with Asperger's are not that great at cognitive empathy but that their emotional empathy does not differ from people without Asperger's, whereas children with conduct disorder show the reverse pattern.

My 11-year-old son is diagnosed with Asperger's, soon to be simply "autism," thanks to impending changes in the DSM5. He is a rowdy giant of an 11-year-old who loves tumbling play with his brothers, but his spirit couldn't be more gentle. When he finds a spider in the house, he carefully gathers it in a tissue and places it outside, alive. He can't bear to watch people crack tree nuts, like pecans, because being something of a tree nut himself, he feels pain on behalf of the nuts. He is so attuned to all of my nonverbal communication that he will recognize and respond to a fluctuation in my mood faster than anyone else in our house, including my husband.

He knows about the Dec. 14 shootings in Connecticut. When he learned about them, his first response was to turn away in the chair where he was sitting, drooping his head over the back. He stayed that way for many long minutes, quiet and still. When he turned around again, my child who rarely, rarely cries, had tears in his eyes. And then, his first urgent concern: That we break from homeschooling and go get his brother, our youngest son and in first grade, from school ... now. And as we drove to the school to pick up his brother, whom I badly wanted to see and hug and hear, my oldest, autistic son voiced what I'd already decided: "Let's not tell him what happened. That's not something he needs to know. It would make him too anxious and scared." Perspective-taking and empathy, you see.

Planned, social violence is not a feature of autism. Indeed, autistic people are far more likely to have violence done against them than to do violence to others. No one knows as of this writing what drove the Connecticut shooter to kill 20 children and 7 adults, point blank, although obvious candidates are rage, hate, a huge grudge against humanity, and some triggering event. But if he turns out to have been someone on the spectrum, I'd like to remind everyone that autism is not an explanatory factor in his actions. And that autistic people like my son are fully, fully capable of empathizing with those who were the target of them.

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ETA, 12/18/12: For anyone who doesn't find my links to studies and summaries addressing these issues sufficient, I refer them to this article by Amy Harmon, at the New York Times, in which autism expert Catherine Lord describes data showing that the autism population is less likely than the general population to engage in planned or extra-familial violence or to use weapons. Also, I am disallowing comments that make unsupported claims that various infamous persons were on the autism spectrum or that engage in armchair diagnoses in general, so don't even bother.

Friday, November 30, 2012

Autism Congressional Hearings: Bingo, vaccines, and some baby steps forward

Saturday, October 27, 2012

NASW meeting: Managing the social media information deluge

Monday, October 8, 2012

Visit me at Forbes!

I've joined the Forbes blogging network, and you can find my first post about a study addressing ADHD behaviors and mercury exposure during pregnancy here. It starts like this:
Maybe you’ve seen a little story today about mercury, pregnancy, fish, and attention-deficit/hyperactivity disorder (ADHD). If you haven’t, you probably will. The news release headline says, “Prenatal mercury exposure may be associated with risk of ADHD-related behaviors.” The modifiers in there “may be” and “related” won’t stop the mental math from this study translating as “pregnant+mercury=ADHD,” and it won’t stop headlines from implying as much. Mix in a confusing finding about eating fish during pregnancy–protective or harmful?–and what’s a science consumer to do? Read more ... 

Sunday, September 30, 2012

Is American conservatism a type of autism? No, but being an offensive lout apparently crosses all borders

Oh, good. Another op-ed with a "hypothesis" about autism. I'll just say, I've seen a lot in the last eight years about autism that's been deeply offensive. But this? This drills through the core of offensive and comes out on the side of calumny. I'd normally let something this burning stupid lie and avoid calling attention to it, but ... this is autism. Nothing is too outre to believe when it comes to autism, and if you don't think people will buy what this guy's selling -- I've got some industrial bleach enemas for you to purchase.

An Australian fellow by the name of Paul Wallis has penned an Op-Ed posted at Digital Journal and entitled, "Is American conservatism a type of autism?" in which he hypothesizes a "social autism" that now afflicts the poor United States of America by way of making conservatives act like autistic people. He proceeds to describe autism as something that it is not and to compare autistic people and their thinking to that of an extreme caricature of conservatism--racist, anti-environmentalist, anti-poor--and uses his hypothesized "social autism" to tell the USofA what a godawful place it is now that everyone acts like autistic people. 

Wallis was asked, apparently by some saint of a human being who mustered some courtesy in doing it, to take down this offensive post. His response?
There was and is no intent to vilify autistic people. If there's an explanation for the idea that there is, I'd like to hear it. I've since contacted L.E.A.N.onUS on Facebook to ask for clarification of their position, which was copied verbatim by Ms. Gammicchia. Until I see adequate information to explain how this article has been so utterly misconstrued, that's my final word on the subject.
I've got your adequate right here, Paul Wallis. First, your description of autism: 
Autism is described as a medical condition whereby people are self-centred, uncommunicative and at a remove from their social environment. There are many different types of autism and degrees of it. A type of “social autism” is also quite possible.
No, autism is not a "medical condition" whereby people are what you describe. Have you ever met an autistic person, even one? It is primarily a condition that involves impairments in social communication, although autistic people communicate all the time, you know, like people do. You think you're making up some kind of "social autism," but autism itself is an inherently social construct the very diagnosis of which is determined by social expectations of communication capacities. Not one thing in any diagnostic criteria I have ever seen for autism describes people who are autistic as being "self centered." I think you're thinking about psychopaths, actually, throughout your garbled screed, not that substituting that word would have made one single thing about your "Op-Ed" defensible. 
Autism ticks all the boxes for behaviour in relation to social issues by conservatives. It seems that there is no society except the one they choose to acknowledge. This is “social autism”, and it comes in many forms.
Your effort here to collect your perceived ideas about what autism is and then shoehorn that into a hypothesized "social autism" afflicting conservatives is an abject failure, in part because one reason conservatives (or liberals) identify as who they are is because of social ties and social biases imparted by their social circles. You see, autistic people tend to be comparatively impervious to this sort of thing. You've created a bizarre oxymoron that's gone meta in how utterly wildly off target it is for characterizing what you're trying to say.

Your post then provides a laundry list about anti-environmentalism, racism, callous dismissal of poverty, and other features you claim are part of US conservatism. Have you been to the United States? Do you know any people who identify as conservative in the United States? I'll grant you this: Like autistic people, they're not something you can just package into a neat little hate box by checking off a list of perceived characteristics they have. They come in all kinds of spectra relative to each of the bullet points you list, from zero to 100% for each point. I know a lot of conservatives, and not one single person fits the grotesquerie you sketch, even in part. My favorite part of your list? Ironically ... you say "social failure is not an issue" in terms of their compassion for others ... while trying to argue that somehow autism is a feature of people like this.

Then you go on, after your silly, inept list, and ask: 
Can this possibly be considered anything but an autistic viewpoint? Even the lying is based on the same mentality as a 2 year old who thinks they can get away with anything. Apparently anything which doesn’t directly benefit or relate to oneself isn’t on the conservative radar. That’s autism, incarnate. There’s 312 million people in America, and evidently most of them are just nuisances according to this mindset.
Wow. You say that this is an "autistic viewpoint," infantilize the population you discuss, call your insanely hyperbolic characterization of US conservatives "autism incarnate," and then you can't tell how you've vilified autisitic people. You list some of the most callous, unemotional attitudes human beings can have about other human beings and the world around them, call that an "autistic viewpoint," and then you--apparently clad in the thickest armor of density and callousness a human can don--can't tell how that vilifies or offends autistic people.

Not sufficient for you, you then go after my country and autistic people like my son, simultaneously:
America has lost something very valuable as a result of this social autism. It has lost its self-respect. No ideology can replace that. People know there will be screw-ups. They know, certainly, that their interests are at the back of the line, if anywhere at all. They know that their needs will not be met. Businesses know that they’re down the bottom of the pecking order and that no amount of “free enterprise” stacks up against insider networks. They can’t compete.
Do you live and vote in the USofA? What do you think we've lost? Our democratic process still exists. We still elect people at all levels of government, from the local to the executive of the land, in that democratic process. Anyone who knows anything about politics or history knows that waves of ideology ebb and flow, that democracies function over the long term, not the short, and that the president of the United States is one human being among the thousands that we, as a nation, elect each year from across ideological spectra. That's our process in action, and it continues to work for us. You blame "social autism" for what you perceive as the ills of this nation, yet you yourself are blind to your own ignorance about both autism and this country.

After insulting wholesale a country, autistic people, and people who identify as conservatives, you received a "very courteous request" from the father of an autistic child to please take down your vile, abusive, irrational, and offensive post. Your response? 
I explained to this gentleman that the entire purpose of this article was to hit the conservatives with their own standards, portraying them as afflicted with a disability. I am absolutely baffled that this piece, which is intended to be an attack on the mindset which appears determined to destroy millions of lives and make poverty, healthcare and social disadvantages worse, could possibly have been construed as any sort of vilification or attack on autistic people. I'm getting attacked by the people I'm trying to protect, and there's not one single word attacking autistic people in the entire 1200 words plus. There are no disparaging references to autistic people at all, anywhere in the text. All references refer to conservative policies and statements on record and proven incidents.
You think you're "hitting conservatives"? You're deluded. All this article does is hit autistic people, mischaracterize the condition, who they are, and how they think and behave, and class them in with a caricatured bogeyman of an American conservative that you constructed as representing all conservative Americans. You claim "you're getting attacked by the people you're trying to protect"? Who asked you for that protection? And where have you put your ears? Because instead of acting like a defensive ass over one of the most offensive articles about autism and my country that I've read in a long time, you need to shut up and listen. And learn. A lot. What you seem to know right now on the subjects on which you've chosen to write doesn't even come close to adequate.

Wednesday, September 26, 2012

Are blogs journalism? Um, no. But they are a journalism medium

Quote:
The silly mantra, 'Information wants to be free,' overlooks the fact that quality information requires effort, and effort costs money. Blogs are all well and good, they add richness to the exchange of information, but they are not journalism, and they never will be.
The above quote comes to us courtesy of Rudy M. Baum, outgoing editor-in-chief of Chemical & Engineering News [ETA: an arm of the America Chemical Society, which seems to have a policy of being dismissive of blogs]. I'm sure his pronouncement would be news to many of the journalists out there who blog and put in a great deal of effort in doing so (or elicit some "again with this shit?" eyerolling), but let's look at his pronouncement one phrase at a time, starting backwards.

"They are not journalism." What is journalism? Definitions vary, but I find the following first definitions:
  • Merriam-Webster: the collection and editing of news for presentation through the media
  • WikipediaJournalism is the investigation and reporting of events, issues and trends to a broad audience. 
  • Pew Research CenterThe central purpose of journalism is to provide citizens with accurate and reliable information they need to function in a free society. This encompasses myriad roles--helping define community, creating common language and common knowledge, identifying a community's goals, heroes and villains, and pushing people beyond complacency. This purpose also involves other requirements, such as being entertaining, serving as watchdog and offering voice to the voiceless.
These definitions do not exclude blogs. In fact, is there a better, more accessible medium for defining community and creating common knowledge and language? 

"Blogs add richness to the exchange of information." Or, they yield new information, breaking news, and deep analysis. You know, journalism stuff. 

"Effort costs money." Not really. Effort mostly costs time. It'd be great if effort and money somehow interacted that way, but as anyone in the writing field can tell you, that ain't how it works.

"Quality information requires effort." See above. Yes, it does. And just because bloggers don't get paid or get paid as much as a staff writer doesn't mean they don't put in effort. 

"Information wants to be free" is a "silly mantra." I'm not sure if he's interpreting the mantra as saying, "We shouldn't have to pay good money for information" or if it means, "Information should not be hidden away." Given the comments that followed this phrase, I'm going with the money interpretation.

The medium used to convey information can be irrelevant to the information's quality. I could do a report on a Big Chief tablet in crayon, but if what I've written is accurate, that's quality information. It won't be pretty, but it'll be good information. If no one pays me for my crayon production, that still doesn't diminish the quality of the information it contains or the effort I put into collecting and writing about that information. If I chose to present my reporting using interpretive dance, assuming I could interpret "The scientists were totally speculating" with dance moves, the medium I choose to communicate that doesn't make or break my report as "journalism." Audience access to it? Maybe. 

Blogs are not, however, Big Chief tablets or interpretive dance. As a medium for journalists, they're a pretty obvious front-runner choice, what with all the writing and journalism-type stuff you can do with them. And bloggers are not wielding crayons or dancing interpretively (that you know). Bloggers who use their blogs to report and break news or analyze it--you know, journalists--are working through one of the most powerful media available today. Blogs are accessible to anyone who can get online. They're not limited by whether or not you've got quarters or a credit card or standard cable. Paywalls don't block them, and a layer of bureaucrats beholden to Rupert Murdoch (usually) has no sway over what a blogger covers. This information does, in fact, want to be free. I can see economic arguments for bemoaning blogs as making information less valuable as a commodity, but that doesn't make them not-journalism.

Can blogs be utterly full of shit? Sure they can. So can Fox News, an alleged journalism medium. Blogs aren't necessarily intrinsically journalism. No. A blogger who is also a journalist--and with that combination, boom! 'Blog can be journalism'--earns an audience because that writer builds trust through effort and hard work and honesty and accuracy. Any journalistic outlet has to do that. Walter Cronkite didn't arrange himself in his news anchor seat in the new medium of television and immediately earn the trust of America. The New York Times didn't emerge on paper as the most-recognized and respected newspaper (at one time) in the country. It earned that trust over time through exacting standards, meticulous reporting, admitting and correcting errors, and great writing. Not one single factor I just listed is something that using a blog as a medium excludes. 

The medium does not determine whether or not a product is journalism. As television demonstrates, a medium is just a tool, something that in the wrong hands can turn out trash, like "Real Housewives of BlahBlah USA." The medium does not determine whether what emerges from its use is trash or treasure--or journalism. The writer--the journalist--dictates that. 

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As I noted in the post, these points have been made before, and I've added links below to two writers who've made them quite memorably. Should we be surprised that it keeps coming up?
From Ed Yong
From Bora Zivkovic

Tuesday, September 25, 2012

Did the rats in the GM corn study drink their water from BPA bottles?

**Updated 90/30/12 at the end of the post.

In my previous post, I noted that the researchers in the now-infamous GM corn/rat study had used polycarbonate cages, rather a no-no when you're doing work with compounds you suspect of being endocrine disruptors. Why? Because polycarbonate plastic leaches bisphenol A (BPA). As it happens, the strain of rats used in this study takes up BPA via the skin quite easily, and BPA in male rats is linked to mammary tumors, which male rats in this study developed. 

As this slide show here indicates (screenshot below), these researchers certainly were aware that they were dealing with a study in the endocrine-disruption context [viewing requires QuickTime], yet they did not take steps to prevent this exposure. Another issue that  experts in this field argue requires special care in such studies (update: despite the broad nature of what's written at that link, according to at least on of the authors, the real concern is only with studies of BPA) that authors appear to have overlooked is using animal feed that could serve as a source of estrogenic compounds. And finally, the biggest no-no of all? Using polycarbonate water bottles, which are known to leach BPA.


When writing the earlier post, I had only information about the cages and the cage supplier the group used. Today, thanks to a Tweet, I got to watch a video that shows the water bottles this research group used, up close and personal. As I'd noted yesterday on this post by Orac at Respectful Insolence, my observations about the polycarbonate cages and the potential influence of bisphenol A leaching were speculative, but certainly less so than the authors' self-debunked hypothesis for the GM corn they used. In that comment, I added, 
if the water bottles were not glass … then what I wrote moves beyond the speculative.
Here are some screenshots from videos that this group has posted to YouTube to promote--surprise!--the anti-GMO movie, Tous Cobayes [All Guinea Pigs]. It starts out with hilariously silly scenes of slow-walking people in scrubs, footies, and face masks that I think were intended to build suspense but that really reflect what any animal tech or researcher has to do every day when entering an animal care facility. It also happens to feature several close-up views of the water bottles this group used to give their 200 study rats access to water for two years. Here are the screenshots.




As you can see, it's a rather unusual-looking bottle, not one I've encountered before in my own work with rodents, using glass bottles. But it's difficult--for me, at least--to tell if it's plastic or glass based on these views. So, I looked for the supplier.

I found the supplier here. It happens to be Genestil, the same France-based supplier of the polycarbonate cages the GM/rat researchers housed those rats in for two years. 
And according to this product description for "biberons" [bottles] that this group's cage supplier offers, the bottle in question, based on a visual match of its unusual three-tiered style, is a 750-ml version that is made of macrolon, also known as ... polycarbonate [PDF]. I don't find glass bottles in their catalog.
If that is true, then this study that the authors knew before the fact likely would involve endocrine disruption subjected 200 rats to two years of living in polycarbonate cages leaching the known endocrine disruptor bisphenol A and sucking down water from bottles leaching the same. For two years. If it is true, it's no wonder their control values overlapped with other values and their data made no sense, even with the Roundup treatments in water.

These are "ifs," I know. And even without these factors, the study falls to the ground for many, many other reasons. But frankly, I'm upset with these researchers. In their zeal, they have treated scientists and their other readers with an off-handed sort of arrogance in the way they obscured their data, tried to manipulate the news media (succeeding, by the way), and concealed conflicts of interest (book! movie! official anti-GMO activism!), apparently based on the assumption that all of us--critics and fans alike--are a bunch of fools who won't see through their oh-so-clever sleights of hand. Fooling people once or twice or three times? That's one thing. But if they wasted 200 helpless rats bursting with tumors (where are those control tumors?) in their crusade and their very basic animal husbandry was an experimental confounder that makes their crazy results totally useless? The rats don't get to choose here. 

I have emailed the contact email on the GM/rat study asking two things. The first is, Was their supplier for the water bottles the same as that for the cages? The second is, Were the bottles they used glass ... or plastic?
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****In an email exchange with a well-known EDC researcher, I've been told that the BPA exposure routes via polycarbonate cages and/or bottles is of specific concern to BPA-related studies only. I don't understand why that is, given the confounding potential of BPA or any other EDC compound in a study involving EDCs, but that's what this investigator said. All that time we spent looking for glassware instead of polycarbonate products, wasted!  Not really. I still argue that in such studies, we need to be as careful as possible to exclude potentially confounding exposures.

Sunday, September 23, 2012

Was it the GMOs or the BPA that did in those rats?

**Updated 9/30/2012, at the end of the post.

It's the study that compromised journalistic integrity, leading some journalists to agree not to obtain outside comment on the paper before an embargo lifted. It's the study that featured shocking images of tumors bursting out all over hapless rats, images reproduced in various stories online in all of their tumoristic, gross morphological horror. It's the study whose authors left themselves open to criticisms from all sides--from science writers and scientists--primarily focused on their strangely lopsided presentation of results--find me the untreated control tumor images in that paper, for example--and their lack of some pretty obvious statistical analyses.

The study in question took a rat strain that's notorious for developing tumors under regular rat-life conditions, fed the rats genetically modified corn, the herbicide Roundup, or genetically modified corn diets possibly laced with Roundup, and evaluated the various groups for tumor burden, liver and kidney outcomes, and mortality. A total of 180 rats received some treatment in their water or diet, while another 20 just lived their regular rat lives eating a regular rat diet. The open-access paper is available here [PDF].

The authors, including anti-GMO activist/scientist Gilles-Eric Seralini, executed statistical analyses that took an almost global hammering on the Web. The special irony here is this paper by Seralini et al., complaining about statistics in toxicology trials Monsanto conducted, particularly related to power analyses and estimations of effect size. They wrote the paper in response to a 2007 expert panel decision rejecting their own analyses of a GM corn as having any effects related to “treatment” with the corn.

In their current paper, the authors conclude that their data demonstrate an effect of a diet containing GM corn, specifically a corn known as NK603, with or without the addition of Roundup, on tumor outcomes and some other endpoints in their two-year rat study. But they may have overlooked some other factors that influenced their results.

Were the diets even different? Maybe not 
For diet to be the culprit here, the diets themselves would have had to be different. One report suggests that the lab chow the authors used itself might have contained GM corn. The authors stated as much in a previous study of NK603 and two other GM corns, observing that the study offered “no data … to demonstrate that the diets fed to the control and reference groups were indeed free of GM feed.” In their current work, they don’t mention this comparison at all; instead, after chemical analyses, they say that “for the different corns and diets, the study of the standard chemical composition revealed no statistical difference” and describe them as having been classified as “substantially equivalent.”

The two factors the authors report as differing among the three diets they describe--regular lab chow, GM chow, or GM+Roundup chow--are caffeic acid and ferulic acid. They assert that these compounds are “not always assayed,” but Monsanto has reported in a peer-reviewed paper on ferulic acid content in NK603 versus non-GM corn and found no difference.

In their discussion, Seralini and colleagues rely on a proposed mechanism for what they found in the rats on ferulic acid in particular. This compound exists in a huge number of plants, including in plants that make up the 84% cereal grain content of the lab chow they used in the untreated rats. Standard lab chows tend to be variable in chemical content. The authors describe having made a laboratory rat chow based on the standard feed they used, except to contain varying percentages of GM corn (that they were aware of) raised with and without Roundup. They also made a “control” chow with non-GM corn at the highest percentage.

When they measured ferulic acid content in their chows, the investigators found that it was lower in their GM and GM+Roundup formulations, with the difference varying by a large range of 16 to 30%. They made up these diets themselves based on a chow with a huge cereal content and chemical variability, so it’s hard to say how relevant these large variations are.

I’m talking about ferulic acid because it’s the compound the authors use to try to explain a proposed mechanism for the presumed effects of the GM corn. They argue that ferulic acid has protective effects against carcinogenesis and mammalian tumors, citing two papers, one that is 28 years old and rather narrow in focus and another from 2010. The 2010 paper reports a positive effect of ferulic acid against chemically induced mammary tumors in Sprague-Dawley rats fed a walloping dose of the stuff. 

They then say that “these phenolic compounds and in particular ferulic acid (sic) may modulate estrogen receptors or the estrogenic pathway in mammalian cells” and cite this paper by Chang et al. Unfortunately for Seralini et al., the Chang paper says that the said “modulation” consists of ferulic acid causing "human breast cancer cell proliferation by up-regulation of HER2 and ERalpha expression.” Based on their own citation, the argument fails that dietary variation in ferulic acid levels--which were substantial in the diets regardless--would have resulted in the results they report. In fact, were GM corn to have lower ferulic acid levels, based on the Chang paper, the GM corn would have been protective.

So what was different if not the diet?
Because I am obsessive, I took the data from this paper and broke it down in the way I’d’ve liked to have seen. This rat strain, as noted, is highly prone to tumors. Each individual rat has an individual propensity to develop tumors, particularly those observed in this study. The authors give us the number of tumors they observed in each group of 10 rats with the number of rats bearing these tumors in parentheses (Table 2 of the paper, which I’ve entered as ratios into the first table given below). Because each individual rat has a high tendency to develop tumors, I think--and feel free to argue this--that the ratio of tumors to number of affected rats in each group might give a better indication of the tumorogenicity of each treatment versus control and clean up the data a little. So, I made those conversions. The second table below contains the original raw data in case the ratios don't suit you.

Then, I did another thing that I wish these authors had done: I compared how these ratios (or raw values) looked within a treatment type (e.g., various doses of GM only, GM and Roundup, various doses of Roundup only). I also looked at between treatments with overlapping variables (e.g., comparing GM11% to GM11%+Roundup), which the authors did for tumors and mortality. These kinds of comparisons should be able to help tease out a little bit which factor--GM or Roundup--might drive differences, if any.

Ratio of tumor/pathology number to rats bearing them for each endpoint. % relates to
%GM corn in diet. R1, R2, and R3=increasing Roundup concentration.



The original data, as presented in the paper (any errors mine). Values are number of observe anomalies per group.
Values in parentheses are number of rats in each group of 10 bearing those anomalies. 
% relates to
%GM corn in diet. R1, R2 (given accidentally as R3 here), and R3=increasing Roundup concentration.
The results are all over the place, whether you look at ratios or absolute number of affected rats or absolute number of tumors or histopathological endpoints. No distinct pattern emerges with GM percentage in the diet. No pattern is there for the alleged presence of Roundup with each diet. I’ve placed the tables showing the graphs at the end of this post for anyone who’s interested. But the graph that interested me--and that reflects the patterns that leapt out at me in Figures 1 and 2 of the paper--is this one below, showing what happens to each parameter with Roundup treatment alone. Remember that these findings reflect ratios of tumor or pathological finding per affected rat, which is most applicable to tumors.

Blue=control; red=lowest Roundup concentration;
green=mid Roundup concentration;
purple=highest Roundup concentration.
The data are messy, but in general, GM vs GM+Roundup seemed to yield quite similar or conflicting results, and control values sometimes overlap or even exceed values from the higher and highest treatment doses. That statement applies whether you view the data as ratios or in the raw data table just above.

But during my first read of this paper, something caught my eye. You can see it in the above figure and in the data in either table, and it also shows up in the mortality and tumor graphs in the paper itself. It’s the inverted U-shaped dose response curve. Was that curve a way to resolve the chaos of these data?

How about those dose-response curves?
As many critiques noted, scarcely any of the data in this paper fit an expected dose response for a carcinogen study--the rates of tumors don’t increase with increasing dose of GM corn or Roundup or both. That kind of linear relationship is typically expected for many toxicology studies--except for those related to endocrine endpoints.

In several cases in this study, at high and low and middle doses of GM corn+Roundup or Roundup, the outcome does not differ from controls. What we do see, and you can see it best in the above figure showing the Roundup treatment data, are inverted U-shaped dose response curves. These curves are classic endocrine response curves, showing a relatively low effect of an endocrine-active compound at high and low doses but a heightened effect at a mid-range dose. Indeed, this kind of curve is almost expected in studies of endocrine-disrupting compounds. The fancy word for these kinds of nonlinear curves, which also can be J-shaped, is hormesis.

Roundup is already known for its endocrine-disrupting capacities, in part thanks to studies like this one from this same author group. But how to explain the scattered nature of the data, including the fact that sometimes, the values for endpoints in the controls exceeded or equaled those for the highest dose of Roundup (a really high dose) or GM corn-possibly-combined-with-Roundup diets?

As I was reading the paper, in addition to noting the hormetic dose-response curves, I noted something else: These rats lived for two years in polycarbonate cages. The protocol does not mention providing fresh cages, but the cages were handled at least twice a week for replacement of litter and contained two rats each. Why do I mention polycarbonate? Because I think it’s possible that one way to explain these whacky-looking data could be the presence of another estrogenic compound, even for controls, that might have influenced outcomes, and that compound is bisphenol A (BPA).

Polycarbonate cages (and possibly water bottles) contain--and leach--bisphenol A
The rats in this long-term study resided in polycarbonate cages for two years. A report from 2003 found that the BPA in these cages can leach out, even at room temperature, even when cages are new. But the leaching kicks up with length of use, with scratches and other marks enhancing the process. This leached BPA affects the animals housed in cages that contain it who also are drinking water from polycarbonate water bottles, according to the 2003 study--and after only one week. The authors concluded that “laboratory animals maintained in polycarbonate and polysulfone cages are exposed to BPA via leaching, with exposure reaching the highest levels in old cages.” 

Another study of an accidental exposure of a female mouse control group to BPA from damaged polycarbonate cages showed that the exposure can result in meiotic abnormalities. One thing that remains unclear about the Seralini protocol is whether or not they used glass or polycarbonate water bottles while the rats also resided in the polycarbonate cages; if the latter, the BPA exposure would have been even greater. This video shows the lab where the rats were kept.

Water bottles or not, rats can take up BPA through the skin. In fact, Sprague-Dawley rats, the kind used in this study, have a skin permeability to BPA that is 12 times that of our own skin. In addition, carcinogenicity studies with BPA show that among the blood-related cancers it might be associated with, it also was associated with … mammary tumors in male rats. This link is of particular interest because, based on a search of relevant terms in PubMed, Roundup doesn’t seem to have been associated with rat mammary tumors. Indeed, the authors point out that it might act to inhibit aromatase, an enzyme that converts androgens to estrogens, and aromatase inhibitors are used to treat breast cancer.

Seralini and co-authors state in their paper that, “As expected, mammary tumors in males occurred far less frequently than in females.” According to a supplier of the rats used in this study, female Sprague-Dawley rats develop exactly the type of mammary tumors seen in this study, with a "high incidence (76%) of mammary gland tumors (predominantly fibroadenomas) (that) resulted in unscheduled sacrifices of many female (s)." Such mammary tumors in these and other male rats, however, appear to occur at a rate of zero. Except when these males are exposed to BPA.
Additional estrogenic disruptor effects from exposing rodents to bisphenol A in these bioassays include an increasing trend for tumors of the mammary glands in male rats (an unusual tumor for males)…. The data for the mammary gland tumors in male rats were 0/50 controls, 0/50 in low dose group, and 4/50 (8%) in the top dose group. …  in my opinion these endocrine tumors should be considered as related to the administration of bisphenol A.
The study cited above involved rats (not Sprague-Dawley) exposed to BPA in their diet for two years. Huff, the author of the linked commentary, concluded, “overall, it appears that BPA exposure via the diet for two years should be considered associated with tumors of the hematopoietic system in rats and mice, and of the testes and of the mammary glands in male rats.”

So, we have probable exposure to compound, BPA, via cages where these rats lived their entire lives. That compound is known specifically to cause mammary tumors in male rats while the treatment in the study is not, and male Sprague-Dawley rats seem to never spontaneously develop these tumors. And we’ve got some pretty obvious hormetic dose response curves that include some relatively high control values, suggesting some underlying endocrine activity. In other words, perhaps we’ve got the wrong three-letter acronym and what we’re seeing here is not the GMOs, it’s the EDCs (endocrine-disrupting compounds).

But that’s not all: What about the soy?
Nothing about the endocrine system is simple, as the curves related to what happens to that system can attest. A part of the diet these rats consumed appears to have contained another exposure to EDCs, in this case plant phytoestrogens, namely those in soy. The diet was about 8% soy and yeast, based on the data from the manufacturer. The concentrations of plant phytoestrogens in rodent diets correlate directly with how much soy they contain, but the concentrations can vary considerably, “and dietary phytoestrogens have the potential to alter results of studies of estrogenicity.” To quote one paper, “Commercial rodent diets are a major source of inadvertent estrogen exposure for laboratory animals.” Diets lacking these compounds are available. 

Questions of additivity or synergy and EDCs
You might be wondering why, if Roundup and BPA and soys and whatever else was present for these rats why the Roundup itself in increasing doses via drinking water didn’t result in rats that were basically one entire tumor at the highest dose. Anyone who’s done research in the field of endocrine disruptors wonders the same, but they can also tell you that these reductive effects with mixtures are more the rule than the exception. My very first study of mixtures taught me that lesson. 

The possible explanations are legion, but with several different kinds of estrogen receptors with different actions in different tissues, compounds that block a receptor at one concentration but activate it at another, compounds that interact with different kinds of hormone receptors in different ways, and differential effects in different species--it’s no wonder the results with mixtures are themselves so mixed. The one thing that doesn’t leap out here as being involved, among a sea of likely possibilities, is the GM corn itself.

The authors were aware of some of this
In their discussion, they note:
As is often the case for hormonal diseases, most observed effects in this study were not proportional to the dose of the treatment (GM maize with and without R application; R alone), non-monotonic, and with a threshold effect.
They don’t mention overlap of many of these endpoints with control results. 

Finally, their findings suggest that sex steroids are also modiļ¬ed in treated rats. That modification implies endocrine-active compounds at work here, and the candidates, to me, at least, are pretty obvious, and they're not corn. A search for endocrine activity related to genetically modified corn turned up one relevant hit, a study that found no effect, in mice using a Bt corn.

Rather than go for the obvious, though (perhaps having overlooked the BPA possibility), the authors sought to construct a fragile argument around one of the two sole differences they found in the GM corn versus the non-GM corn in caffeic and ferulic acid levels. As I noted above, their speculation of GM implication falls apart based on their own citation of a study suggesting that ferulic acid enhances proliferation of breast cancer cells. They also appear to have evaluated not the GM corn itself but the diet containing other ferulic acid sources as a whole for these values, and their finding of a difference in ferulic acid content counters that of a peer-reviewed Monsanto study finding equivalent values in a direct corn-to-corn comparison.


Thus, their efforts to implicate GM corn in their findings in this study rely on a failed speculation. They might have better spent their time considering the various confounders their experimental protocol introduced that could have directly affected their experimental endpoints. At least that might have pulled some signal from all the noise of their data.

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ETA: I take a look at the water bottles the group used for their rats for the two-year study here. Please note that anything about BPA is simply speculation, as no one measured BPA exposure, and there's certainly enough wrong with this study design, analysis, and presentation that's right in front of us without having to turn to BPA to explain why their controls seemed to have been as affected in some endpoints as their treatments. I emailed both the contact email for the paper and the supplier about the bottles; neither has responded.

**Finally, in an email exchange with an EDC researcher, I've been told that the BPA exposure routes via polycarbonate cages and/or bottles is of specific concern to BPA-related studies only. I don't understand why that is, given the confounding potential of BPA or any other EDC compound in a study involving EDCs, but that's what this investigator said. All that time we spent looking for glassware instead of polycarbonate products, wasted! Not really. I still argue that in such studies, we need to be as careful as possible to exclude potentially confounding exposures.

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More tables graphs, just for fun.


1=controls; 2=11%GM corn in diet; 3=11%GM corn+Roundup
used on corn when grown (concentrations unknown).
Four is a creator error. Values are ratio of tumors
to number of rats bearing tumors.

1=controls; 2=22%GM corn in diet; 3=22%GM corn+Roundup
used on corn when grown (concentrations unknown). 
Values are ratio of  tumors/histo findings
to number of rats bearing tumors
.

1=controls; 2=33%GM corn in diet; 3=33%GM corn+Roundup
used on corn when grown (concentrations unknown). 
Values are ratio of tumors/histo findings
to number of rats bearing tumors
.


Comparison of GM percentage in diets and effects on tumors/histopathology.
Blue=control; red=11%; green=22%; purple=33%.
Values are ratio of
 tumors/histo findings
to number of rats bearing tumors.

Comparison of percentage of GM corn exposed to Roundup in diets
and effects on tumors/histopathology. Blue=control; red=11%GM corn+Roundup;
green=22%
GM corn+Rounduppurple=33% GM corn+Roundup. Values are ratio of tumors/histo findings to number of rats bearing tumors.