Friday, September 13, 2013

Genetically Modified Organism (GMO) Scare Tactics




Let’s talk about rats.  That’s right, rats.  Specifically, Sprague-Dawley rats.

It turns out that Sprague-Dawley rats are very susceptible to getting spontaneous cancers.  All kinds of cancers—pituitary, mammary, pancreatic, adrenal, liver, thyroid, ovarian, uterine, prostate, skin, kidney, bladder, stomach, brain . . . you get the idea.   This is the reason that these rats are commonly used for carcinogenic studies.  Makes sense—if you want to find out if a compound is carcinogenic, you might as well start out with an animal that is prone to getting cancer.  Even if you do absolutely nothing to these rats, between 50% and 70% of them will develop some kind of neoplasm (any abnormal growth of tissue, whether benign or lethal).

But if you knew that 50% would develop a neoplasm of some type, how many cancers above 50% would you need in order to “prove” that your chemical caused cancer?  Well, this is the kind of statistical problem that scientists face all the time:  how do you show that the effect of the chemical is not due to chance alone, like flipping a coin?

First of all, you need LOTS of rats.  I think that’s intuitively obvious, especially if you’ve ever flipped coins.  If you flip only 10 times, you might get 10 heads in a row, but if you flip 1,000 times, you’ll get a lot closer to the statistically-expected 50/50 split between heads and tails.

So how many rats do you need?   Well, the scientific world has decided that 50 rats per treatment is a minimum for these kinds of carcinogenic studies.  The Organization for Economic Co-operation and Development recommends “at least” 50 animals per group.  The Environmental Protection Agency states: “Current standardized carcinogenicity studies in rodents test at least 50 animals per sex per dose group in each of three treatment groups and in a concurrent control group, usually for 18 to 24 months, depending on the rodent species tested . . . .”

By now, you are probably wondering why I’m going through all of this.   The answer is that a 2012* paper published in a respected scientific journal DID NOT follow these guidelines. 

They didn’t even follow the guidelines for a well designed high school science project.

And yet their paper is being used by the press to “prove” that genetically engineered crops (“genetically engineered organisms” or “GMOs”) are undesirable.  This has caused hysteria around the world—and some of that hysteria is on the part of scientists who want the paper retracted.

Before we get into the nitty-gritty of the experiment, we need to know what the term “genetic engineering” really means.  There are some people who would say that ANY plant breeding constitutes genetic engineering, even the old-fashioned kind that involves transferring pollen by hand from one plant to another.  But in the context of the GMO debate, most people would say genetic engineering consists of moving individual genes from one organism to another using molecular biology techniques developed since the 1970’s.   And for our purposes here, all we need to know is that DNA, the chemical that makes up genes, can be extracted from any known organism and transferred to nearly any other known organism.  Genes can be moved from bacteria to humans, for example—with a high degree of precision.  They can be “engineered.”

And with that little bit of background, here’s the experiment that caused all the furor:

The test subjects were Sprague-Dawley rats that were fed a diet including various percentages of corn.  The “normal” (control) group received 33% non-GMO corn, and the remaining rats received either 11%, 22%, or 33% GMO corn.  The experiment ran for two years, during which time the researchers kept track of the number of rats that died and those that got one or more cancerous growths. 

There were 10 rats in each treatment group for each sex.  When you do the math, it turns out that with an expected 50% baseline Sprague-Dawley mortality rate, it takes 9 rats in a single group to die (or survive) in order to “prove” with statistical significance that the cause was something other than chance.

Here is the mortality data for each treatment group in the study—

Number of deaths (male rats)
Non-GMO Corn
11% GMO
22% GMO
33% GMO
3
5
1
1


Number of deaths (female rats)
Non-GMO Corn
11% GMO
22% GMO
33% GMO
2
3
7
4

So, in six of the eight treatment groups, the number of deaths was no different than what you would expect get a coin toss—remember that because these rats are bred to get cancer, an average of 5 in each group would die regardless of their diet.  And what about the other two groups, the ones that had only one death apiece?  Statistically, those results ARE significant because fewer rats in these groups died than predicted by chance alone.  The conclusion?  Since these rats were fed the two highest rates of GMO corn, it must have been good for them.  HA!

Now, the baseline mortality rate I used for these calculations was 50%, but the mortality rate for Sprague-Dawley rats over the course of two years can be as high as 70%.  If we do the same calculations again but with a 70% baseline mortality rate, it turns out that ALL the rats in a given treatment group would have to die or survive in order for the results to have any statistical significance.

The point here is that the number of rats assigned to each treatment group in this study is entirely too small for the results to be at all meaningful.  This is highlighted by the fact that the data show no relationship between the mortality rate for a given treatment group and the “dose” of GMO corn in that group’s diet.  After all, if a particular substance actually caused the rats to die, you would expect the rats receiving the most of that substance to have the highest mortality rate—but just the opposite was observed in this study. 

So what this means is that all of the study data is apparently just random statistical noise. 

Which raises an interesting question—why did the researchers use such small numbers of rats?  Were they really incapable of designing a robust, meaningful study? Or did they just WANT to generate mortality in treatment groups as cheaply as possible in order to raise an alarm?

I must say that upon a quick glance, the original paper is scary.  The raw data is arresting (35% of the rats in the GMO groups DIED), the accompanying photographs of gigantic tumors are lurid, and reports of pituitary cancer are enough to frighten anybody.  It is only after doing some homework that you begin to realize that these same results are found in a high percentage of ALL Sprague-Dawley rats. 

Furthermore, a 2012 review paper that looked at GMOs in 24 studies for maize, soybeans, potato, rice, and triticale found NO papers showing that GMO crops have any negative impact on health.  Perhaps we shouldn’t be surprised that the authors of the Sprague-Dawley rat study do not cite any of these papers.

A related issue has to do with the “composition” of GMOs.  There has been a concern ever since the introduction of GMO crops that their protein and/or carbohydrates and/or fats had somehow been altered by the introduction of new genes.  This has never made any sense to me—I mean, is it really likely that an herbicide-resistance gene would affect the fat content of soybeans?  But under the theory that the nutritional content of GMOs might somehow be different from that of varieties produced by traditional means, the “compositional equivalence” of GMOs has been examined since 1993 (thus adding about $1 million dollars to the cost of producing a new GMO variety).

In fact, in Europe at least eight field sites must be used, with each site to include both GMO and non-GMO lines for comparison purposes. 

Let’s be clear here: “traditional” plant varieties, produced by conventional techniques, do NOT require any type of compositional testing—even though traditional plant breeding has the potential to cause radical changes in the genome.  For example, if ancestral parents are crossed with modern varieties, very strange progeny can result; a virtual “earthquake” of random genetic effects can be induced, including newly-introduced genes that have not been seen in the modern varieties for thousands of years.

In my opinion, GMOs are subjected to additional requirements not because of rational scientific concerns, but rather because of fear on the part of the general public—these additional tests are just roadblocks designed to prevent or delay the introduction of new GMO crops.

This is borne out by a 2013 paper that reviewed 20 years’ worth of GMO studies covering corn, soybeans, cotton, canola, wheat, potato, alfalfa, rice, papaya, tomato, cabbage, pepper, raspberry, and mushrooms.  Guess what they found?  GMOs are compositionally indistinguishable from non-GMOs.  In fact, plants produced by “traditional methods” show more variation in nutritional composition than GMOs do.  Which actually makes sense given the various ways genetic variation is introduced using conventional techniques (radiation, chemical mutagenesis, somaclonal variation, wide crosses). 

And in the same vein as the Sprague-Dawley rat study, there is yet another 2013 paper that is being used by some parties to show that GMO crops do not have a yield benefit.  Now, if this is in fact the case, why are farmers growing GMOs?  I mean, millions of acres of GMO crops are planted worldwide, including 90% of the corn, cotton and soybean acreage in the United States alone.  If there is no benefit in terms of yield, I would have to conclude that all of these farmers are just plain dumb.  Since that seems unlikely, one has to wonder if perhaps there is another explanation.

So, once again, we need to look at the paper to see what the data actually says. 

For this study, 4,748 hybrid corn varieties were grown across Wisconsin from 1990 to 2010.  2,653 of these varieties were conventional hybrids (non-GMO), and 2,095 were GMOs.  (My first thought is to question how 4,748 hybrids could possibly be developed for a minor corn-producing state like Wisconsin and consequently, how well any of these hybrids were adapted to growing conditions there.  I would rather have seen this study performed in Ohio or Illinois.)

The GMO varieties were divided into 12 groups: one group was tolerant to Round Up herbicide; another was tolerant to glufosinate herbicides; another produced Bacillus thuringiensis (Bt) toxin against European corn borer; another produced Bt toxin against corn root worm.  Some hybrids had two-way gene combinations, such as resistance to both Round Up and corn rootworm, and others had three-way combinations. 

The study data show that three of the GMO groups had yields that were statistically lower than the conventional hybrids, three of the GMO groups were statistically superior to the conventional hybrids, and the remaining six groups were statistically the same as the conventional hybrids.  So on average, it appears that the GMO yields are equivalent to the non-GMO yields, and this is what is being touted by the GMO naysayers.  But what they ignore is that ALL of the GMO crops had greater STABILITY than the conventional hybrids. 

Why is this important?   Because when a crop has “stability”, it consistently gives the same yield from one year to the next and from one environment to another.  This means less risk for the farmers because they can plan on getting a certain yield from their crop every year, even if it is grown in a different place or under different conditions.  The risk-reduction benefits of crop stability are so predictable that agricultural economists attach an actual value to it (called a “risk premium”).  In other words, they can predict the added economic benefit that will accrue to the farmer from growing a particular high-stability, low-risk variety.  That benefit is expressed in terms of bushels/acre because it is equivalent to the increase in profit that would result if yields increased by a certain amount.

In the Wisconsin corn study, the researchers showed that the reduced risk due to the stability of the GMO varieties was equivalent to an increase of 0.78 - 4.19 bushels/acre over the actual yield.

So even the studies that were apparently designed to show genetically-engineered crops in a bad light were unable to do so.  This is due to the fact that genetic engineering is closely aligned with a phenomenon known as “horizontal gene transfer,” which is the transfer of genetic information between different species in the absence of mating—something that nature has been doing for, oh, about 500 million years.  And horizontal gene transfer is not limited to the transfer of genes between closely related organisms.  A 2012* paper showed that a particular moss had acquired 57 different families of nuclear genes from bacteria, fungi, and viruses.  These genes are related to vascular development, cuticle and epidermis, hormones, stomata pattern, herbivore resistance, plastid development and pathogen resistance. 

Now, that is genetic engineering on a grand scale!

My point is that plants/animals/bacteria/viruses/fungi have been mixing it up for millions of years, and genetic engineering by the hand of man is not inherently different from genetic engineering by Mother Nature.

Useful references:

**http://research.sustainablefoodtrust.org/wp-content/uploads/2012/09/Final-Paper.pdf


http://pubs.acs.org/doi/full/10.1021/jf400135r


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