Pollan and Bittman, the Morano and Milloy of GMO anti-science

Why do food writers think they are competent to evaluate the scientific literature? I know of at least two who, based on their tweets, clearly are not. One is Mark Bittman, who we have previously chastised, and now also Michael Pollan who has been a bit more coy about promoting anti-science related to GMO. Now they’ve both been broadcasting the flimsy results of this paper – A long-term toxicology study on pigs fed a combined genetically modified (GM) soy and GM maize diet – published in the “Journal of Organic Systems”. Why do I feel like I’m reading headlines from Climate Depot or Milloy’s Junkscience? Because it’s the exact same behavior.

For all you budding science journalists out there, here is your first red flag, novel groundbreaking research is rarely reported in a such journals. Not to demean the smaller journals, good science is done there, but the quality of the publications must be one of the first factors taken into account when evaluating the significance of results published in the lay press. Note Reuters and Huffpo both published fluffy repetitions of “press release” evaluations of the study. Neither appears to show any skepticism or depth into the significance of the results, other results within the paper, or whether the fundamental conclusions of the authors are even supported by the data. Let’s do this now.

First, let’s describe the study. It’s a long-term (22.7 week) feeding study in pigs, with two groups of 84 pigs randomly selected to either receive GMO feed or non-GMO feed. During the trial all conditions are controlled, the feeds are found to be nutritionally identical (interesting given how GMOs has no nutrients!11!!!), and were obtained according to standard practices of pig farmers from similar local sources. The pigs were raised to the standard age they are when they go to slaughter, and were then killed and their bodies autopsied. While living the animals were evaluated by weights weekly, level of activity of pigs, level of contentment, skin problems, respiratory problems, eye problems, stool quality, blood biochemical analyses right before slaughter, and mortality. At autopsy organs were weighed and evaluated by veterinarians for evidence of tissue pathology.

Second, the findings. A good science journalist determines these by looking at the data, not by repeating whatever the authors tell them. Looking at the data there were no differences in any of the major variables evaluated by the study, such as weights, veterinary costs, illnesses, or mortality. No significant differences in blood biochemistry were found. At autopsy most organ weights were similar between groups. There was a statistically significant (but likely clinically-meaningless) increase (0.1kg vs 0.12kg) in uterus weights in the GM group. At pathology there were nonsignificant decreases in cardiac and liver abnormalities in the GM group (half as many), in stomach pathology there was one significant finding of more “severe inflammation” (on a 4-point scale from no inflammation to severe) in the GM group. This is the finding that has been amplified as variably “damning” or “concerning” depending on which source is reporting these dramatic new findings.

But since we’re skeptics here (real skeptics not like global warming “skeptics” in scare quotes) we ask, is it really?

Lets take a closer look at the data in table 3. Here are the relevant numbers:
Carmentable3data

While it is clear that along the severe inflammation row there is a difference, look at the moderate inflammation row immediately above it, and see if it changes your mind. What if we were to combine this table into a binary, no to mild inflammation vs moderate to severe? The numbers become GMO 41, non GM 38. Why would I look at it this way? Because pathologic scales of things like inflammation are subjective. (***Update It has been pointed out that the authors also didn’t actually do tissue pathology, instead they just graded how red the stomachs were on gross pathology, which also makes this assay totally meaningless. See full update below***) One should be very cautious about results presented on such a scale representing true differences especially given the next nearest population on the scale is reversed and eliminates your effect when the two groups are combined. Trying to make this objective data to suggest an association is very much trying to cram a square peg through a round hole, and would not fly on most reviewers’ reads of this data, and if I had been a reviewer I would have squashed this on this point alone. The fixation on one single data point in this table to the exclusion of the others and building the conclusions around it is unscientific. One needs to be a lot more cautious given the design of this study. Let me explain.

This is not hypothesis-driven work. They authors did not at the outset say, “we propose stomach inflammation will be greater in GM fed pigs because of x”. No. What they did was feed pigs two different diets and then go fishing for abnormal values. This is not necessarily wrong behavior, scientists go on fishing trips all the time looking to find significant effects. What is wrong is then publishing the results of your fishing trip! This is unscientific.

If you were to study some 20 variables in your study (these authors studied far more variables and I would actually expect more abnormal results then we have), and have a cutoff for significance at the standard arbitrary value of p = 0.05, one would expect, just by chance, that 1 of those variables will be significant. A good scientist then says, “well that’s interesting, let’s see if it’s real”, and then follows this study with a hypothesis-driven study specifically designed to study the apparent effect. When the single effect is then studied in isolation, with appropriate power, one should see if the result you found, perhaps by chance, is a real effect or not.

So what we have in this study is the first half of a valid study (the fishing trip) but no real hypothesis driven research to confirm if this 1 in 20 result is real. There is no molecular data to suggest a mechanism. They don’t further determine if it was the soy component or corn component on the diet. There are no follow up evaluations examining this effect alone, or trying to link ingestion of cry proteins on stomach inflammation. So far, one can only conclude that it’s just as likely that this result occurred by chance as it is to be an actual effect of feeding the pigs GM corn and soy. Now, is that “damning” or “concerning”? Concerning is even a stretch.

Third, it’s important for the good science journalist to interpret these new findings in the context of the literature, and perhaps consult an expert in the field to determine the significance of these results in context of the total knowledge in the field.

One should mention the extensive literature on the safety of GM foods. Other writers including Mark Lynas have evaluated this paper as well with similar conclusions as mine. Additionally, Mark points out the paper’s favorable interpretation of Seralini’s work – a bad sign. The authors appear to have ties to anti-GMO advocacy groups, and even thank Jeffrey Smith (the hysterical anti-GMO fake expert with no scientific or medical training). Andrew Kniss points out that he can’t replicate their result with the appropriate statistical test. I admit, I am confused about exactly how they calculated the p value, as in their methods they describe using t tests, Mann-Whitney and Chi Squared variably based on the distribution or categorical nature of the variables, so half the time reading I was trying to figure out which test they were using at any given moment. I’m still unsure exactly why they chose to do which test in each instance – in table 5 they appeared to switch between a Wilcox and a t-test at random. Although in table 3 they appear to have used a Uncorrected Chi squared based on the footnote, I’m not exactly sure, based on how one could be constructed with different expected values, if this was appropriate. No statistical expert am I, but again this smells a bit like statistical fishing to me. Even so, it doesn’t change the relevance of the results. Even if it does technically pass statistical muster, it’s still just the first step in a real scientific investigation. Another GMO expert suggests given the levels of mold they measured on their GM corn, it could have been a result of their source selling them moldy feed (at levels much higher than are usually found on GM crops).

So, to summarize, in this paper the authors performed a large non-specific screen for potential evidence of harm from GM crops. Of the many analyses performed, one showed statistical significance for severe stomach inflammation on a pathology scale in the GM group, but this effect rapidly-disappears if one groups inflammation based on broader categories. The clinical significance of this finding can only be determined by subsequent hypothesis driven research into this potential effect, but it is equally likely this is a result of random chance.

Or you can skip all the words above and read the XKCD one of Mark Lynas’ commenters suggests

XKCD knows stats

A final note, I’m not interested in comments saying I work for Monsanto, that I’m a corporate shill, blah blah blah. I haven’t worked for, or accepted money from, a corporation in my adult life (excluding Nat Geo sending me beer money for this blog, and working as a valet for Toyota dealership when I was 16). Address the data, the paper, relevant biological arguments etc, or get lost.

**Update**
In reading an additional response to the Carman et. al study, I now change my opinion on this paper from “competently performed but meaningless” to “totally meaningless”.

At issue is a criticism by Robert Friendship in the link above, that the author’s assay for inflammation is basically meaningless. In my initial read of the paper I didn’t notice this sentence “Typical examples of each of the four categories of inflammation are shown in Figure 1. For a severe level of inflammation, almost the whole fundus had to
be swollen and cherry-red in colour.”

I incorrectly assumed the authors had taken sections, performed histology, then assessed inflammation based on a legitimate pathological scale. This was apparently too generous. No, they just looked at the color of the stomach by gross pathology. As Dr. Friendship points out, this is meaningless.

Anti-GMO writers show profound ignorance of basic biology and now Jane Goodall has joined their ranks

It’s a sad day for the reality-based community, within the critiques of Jane Goodall’s new book ‘Seeds of Hope’ we find that in addition to plagiarism and sloppiness with facts, she’s fallen for anti-GMO crank Jeffrey Smith’s nonsense.

When asked by The Guardian whom she most despised, Goodall responded, “The agricultural company Monsanto, because I know too much about GM organisms and crops.” She might know too much, but what if what she knows is completely wrong?

Many of the claims in Seeds of Hope can also be found in Genetic Roulette: The Documented Health Risks of Genetically Engineered Foods, a book by “consumer advocate” Jeffrey Smith. Goodall generously blurbed the book (“If you care about your health and that of your children, buy this book, become aware of the potential problems, and take action”) and in Seeds of Hope cites a “study” on GMO conducted by Smith’s “think tank,” the Institute for Responsible Technology.

Like Goodall, Smith isn’t a genetic scientist. According to New Yorker writer Michael Specter, he “has no experience in genetics or agriculture, and has no scientific degree from any institution” but did study “business at the Maharishi International University, founded by the Maharishi Mahesh Yogi.” (In Seeds of Hope, Goodall also recommends a book on GM by Maharishi Institute executive vice president Steven M. Druker, who also has no scientific training). As Professor Bruce Chassy, an emeritus food scientist at the University of Illinois, told Specter, “His only professional experience prior to taking up his crusade against biotechnology is as a ballroom-dance teacher, yogic flying instructor, and political candidate for the Maharishi cult’s natural-law party.” Along with fellow food scientist Dr. David Tribe, Chassy runs an entire website devoted to debunking Smith’s pseudoscience.

And it apparently escaped Goodall’s notice that Smith’s most recent book—the one that she fulsomely endorsed—features a foreword by British politician Michael Meacher, who, after being kicked out of the Tony Blair’s government in 2003, has devoted a significant amount of time to furthering 9/11 conspiracy theories.

Goodall is, of course, not the first scientist of fame and repute to fall in for crankery and pseudoscience. From Linus Pauling to Luc Montagnier, even Nobel Prize winning scientists have fallen for psuedoscientific theories. However, we should always be saddened when yet another famous scientist decides to go emeritus and abandon the reality-based community.

There always seem to be a couple of different factors at play when this happens. For one, such scientists appear to have reached a such a status that it becomes very difficult for others to criticize them. It’s like a state of ultra-tenure, in which you practically have to insult the intelligence of an entire continent before people will object to your misbehavior. The second common factor seems to be that they start operating in a field in which they lack expertise, but seem to assume their expertise in other unrelated fields should allow them to waive in. This appears to be the case with Goodall, as even someone with rudimentary knowledge of molecular biology should be able to see the gaping holes in the anti-GMO movement’s logic.

For example, let’s start with the easy-pickings at Natural News. A recent article by Jon Rapaport entitled “Brand new GMO food can rewire your body: more evil coming” is a perfect example of how the arguments made against GMO foods are based on fundamentally-unsound understanding of biology. The author writes:

It’s already bad. Very bad. For the past 25 years, the biotech Dr. Frankensteins have been inserting DNA into food crops.

The widespread dangers of this technique have been exposed. People all over the world, including many scientists and farmers, are up in arms about it.

Countries have banned GMO crops or insisted on labeling.

Now, though, the game is changing, and it’ll make things even more unpredictable. The threat is ominous and drastic, to say the least.

GM Watch reports the latest GMO innovation: designed food plants that make new double-stranded (ds) RNA. What does the RNA do? It can silence a gene. It can activate a gene that was silent.

If you imagine the gene structure as a board covered with light bulbs, in the course of living some genes light up (activation) and some genes go dark (silent) at different times. This new designed RNA can change that process. No one knows how.

No one knows because no safety studies have been done. If you have genes lighting up and going dark in unpredictable ways, the functions of a plant or a body can change randomly.

Pinball, roulette, use any metaphor you want to; this is playing with the fate of the human race. Walk around with designer-RNA in your body, and who knows what effects will follow.

At this point, I think anyone familiar with the science of RNA interference (RNAi) has slapped themselves in the forehead, for anyone who wants a decent introduction the Wiki does a pretty good job. It’s clear that the author is projecting his own ignorance of RNAi onto the rest of us. Briefly, until about 20 years ago, the so-called “central dogma of molecular biology” was a one way road from DNA being transcribed into RNA which was then translated into a functional protein. Even this is a pretty gross simplification, but it’s fair to say, that prior to the discovery of RNAi, RNA was thought to be little more than a messenger in the cell, serving as an intermediary between the DNA code, and the protein function. Yes, we knew that some RNA had enzymatic function, was incorporated into some proteins, etc., but it wasn’t seen so much as a regulatory molecule.

Then, after a few intriguing findings in plants, Fire and Mello discovered that RNA itself could control the translation of other genes in c. elegans. Almost by accident, they found that if you inserted a double-stranded RNA molecule corresponding to a RNA transcript, that transcript would be degraded and the protein it encoded for wouldn’t be expressed. It was a surprising finding. One would think that what would work would be the anti-sense strand of RNA that would bind the sense strand and somehow inhibit it’s entry into the ribosomal machinery and ultimately interfere with translation. Instead, what they found was double-stranded RNA had a function all of it’s own, with a previously unknown cellular machinery specifically-purposed with processing dsRNA and inhibiting gene function through an entirely different mechansim. Subsequently we’ve also found the RNAi not only can directly regulate the levels of RNA transcripts, but can also regulate gene suppression, and activation directly on promoter sequences on DNA itself.

It’s amazing, decades after the discovery of RNA and understanding of its primary function, we discovered this new and incredibly complex layer of regulation of genetics by RNA molecules involved in everything from development to disease. But what does that mean for us? Should we be worried about gene-regulating RNA molecules in our food?

Of course not! RNAi is an intrinsic function of most eukaryotes. Just about every food you’ve ever eaten in your entire life is chock-full of RNA molecules, including double-stranded inhibitory RNAs involved in the normal biological processes occurring within the cell. If other organisms could affect us by poisoning us with RNA, we wouldn’t last a minute. Weirdly, in GMO paranoia world, however, whatever we consume has the potential to take over our bodies. The basic molecules of all life, that exist in everything we eat, take on new powers once handled by human scientists. The article hinted at as evidence of this risk (but of course not actually cited by the author) that suggests miRNA may have “cross-kingdom” effects, is a great example of crank cherry-picking, as the evidence demonstrating it may be artifact is of course not mentioned. And we shouldn’t be surprised, as it would be a pretty extraordinary hole in our defenses if other organisms could so easily modify our gene expression.

One of the great limitations of gene therapy as a potential therapy has been that it’s extremely difficult to introduce genes, or specifically regulate them with external vectors. If it were as simple as just feeding us RNA that would be something. For better or worse (likely better), your body is extremely resistant to other organisms tinkering with its DNA or cellular machinery.

Ok, but then you say, “Hey, that’s Natural News, we know they’re morons.” Ok, how about Clair Cummings in Common Dreams panic-posting about the GMO threat to our water supply from this week? Great evidence that “progressive” is no insulation from “anti-science”:

Today is World Water Day. The United Nations has set aside one day a year to focus the world’s attention on the importance of fresh water. And rightly so, as we are way behind in our efforts to protect both the quantity and quality of the water our growing world needs today.(Image: EarthTimes.org)

And now, there is a new form of water pollution: recombinant genes that are conferring antibiotic resistance on the bacteria in the water.

Researchers in China have found recombinant drug resistant DNA, molecules that are part of the manufacturing of genetically modified organisms, in every river they tested.

Genetically engineered organisms are manufactured using antibiotic resistant genes. And these bacteria are now exchanging their genetic information with the wild bacteria in rivers. As the study points out, bacteria already present in urban water systems provides “advantageous breeding conditions for the(se) microbes.”

Antibiotic resistance is perhaps the number one threat to public health today.

Transgenic pollution is already common in agriculture. U.C. Berkeley Professor Ignacio Chapela was the first scientist to identify the presence of genetically engineered maize in local maize varieties in Mexico. He is an authority on transgenic gene flow. He says it is alarming that “DNA from transgenic organisms have escaped to become an integral component of the genome of free-living bacteria in rivers.” He adds that “the transgenic DNA studied so far in these bacteria will confer antibiotic resistance on other organisms, making many different species resistant to the antibiotics we use to protect ourselves from infections.”

Our expensive attempts to filter and fight chemicals with other chemicals are only partially effective. Our attempts to regulate recombinant DNA technology has failed to prevent gene pollution. The only way to assure a sustainable source of clean water is to understand water for what it is: a living system of biotic communities, not a commodity. It is a living thing and as such it deserves our respect, as does the human right to have abundant fresh clean water for life.

You heard it, now they’re making up a new category of pollution “gene pollution”.

Let’s go back to some of the basic science here, so again, we can display just how silly and uninformed these Chicken Littles are. When molecular biologists wish to produce large quantities of a DNA or protein, what they usually do is insert the sequence into an easy-to-grow organism like E. Coli, or yeast, or some other cell, and then have the biologic machinery of those cells produce it for us. This is one of the most simple forms of genetic modification, and we use it from everything to making plasmid DNA in the lab, to the production of recombinant human insulin for diabetics. In order to make sure your organism is making your product of interest you include a gene that encodes for resistance to an antibiotic (in bacteria most commonly to ampicillin) so that when you grow your bug you can make sure the only cells growing are the ones that are working for you by including that antibiotic in the mix. Other resistance genes we use are often for antibiotics we don’t use in humans, like hygromycin or neomycin, which is nephrotoxic if injected (but also poorly absorbed).

“That’s terrible!”, you say, “how could we teach so many bacteria to be resistant to antibiotics! Surely this will kill us all!”

Um, no. For one, the resistance genes we use aren’t novel or made de novo by humans, they already existed before a single human was ever treated with an antibiotic. The first antibiotic discovered, penicillin, is a natural product. It’s an ancient agent in an ongoing war between microorganisms. The antidote for penicillin and related molecules was actually discovered at about the same time as we discovered penicillin. Beta-lactamase, which breaks open the structure of the penicillins and inhibits their antibiotic effects was around long before humans figured out how to harness antibiotics for our own purposes. The gene, which we clone into plasmids to make our GMO bacteria work for us, came from nature too. Now if we were growing bacteria in vancomycin or linezolid, yeah, I’d be pissed, but that’s not what’s happening. And even though we still use older penicillins clinically, it’s with full knowledge that resistance has been around for decades, and they are used for infections that we know never become resistant to the drugs, like group b strep (or syphilis). The war for penicillin is over. We lost. Any bug that’s going to become resistant to penicillin already is.

The antibiotic resistance that plagues our ICUs and hospitals doesn’t come from GMOs being taught to fight ampicillin, it comes from overuse of more powerful antibiotics in humans. The genes that are providing resistance to even beta-lactam resistant antibiotics like the carbapenems or methicillin are the result of a more classic form of genetic modification – natural selection.

So what is the risk to humans from the DNA encoding a wimpy beta-lactamase or whatever being detected in water? Zilch. Nada. Zip.

The paranoia over recombinant DNA has persisted for decades despite no rational basis for a threat to humans or other living things. The continued paranoia over rDNA is a sign that the GMO paranoids get their science from bad movies, not textbooks or serious knowledge of the risks and benefits of this technology. rDNA is why we have an unlimited supply of insulin, it’s how we have virtually all of our knowledge of molecular biology, it’s how we even have an understanding of how things like antibiotic resistance work. It’s been around since the 70s and how many times have you heard of it actually hurting a person?

This is the state of the argument over genetically-modified organisms. To the uninitiated this stuff sounds like it might be kind of scary. But with any real understanding of the molecular mechanisms of these technologies, the plausibility of their risk drops to zero. Sadly, Goodall has not only shown a pretty poor level of scholarship with this new book, but also, has fallen in with cranks promoting implausible risks of this biotechnology. It’s unfortunate because she should be respected for her previous work as an environmentalist and a conservationist. This is what is so annoying about anti-GMO paranoia. It makes environmentalists look like idiots, as it distracts from actual threats to the environment with invented threats and irrational fears of biotech. I’m sure I’ll now be accused of being in the pocket of big ag, as I am in every thread on GMO, but I assure you, I have no financial interests, or any dealings with these companies ever. I’m irritated with the anti-GMO movement because it’s an embarrassment. It’s Luddism, and ignorance masquerading as environmentalism. It’s bad biology. It’s the progressive equivalent of creationism or global warming denial. It’s classic anti-science, and we shouldn’t tolerate it.