Nathan Daley, MD, MPH, Green Med Info
Waking Times

OMG, GMOs!

You might ask, “why all the fuss about agricultural genetically modified organisms (GMOs)?” After all, regulatory agencies have approved these technologies for widespread application and consumption, so they must be safe, right?  Well, the truth is that there is no agency and no industry that  works to protect our health.  At best, the EPA, USDA, and FDA attempt to respond to our disease after the cause is widespread.  At that point only risk reduction, rather than risk avoidance, can be achieved.  This has been the case historically with radium paint, tobacco, particulate air pollution, water pollution, asbestos, lead, food-borne illnesses, and DDT.  A number of the various 80,000 chemicals in production will likely be added to this list in the future while the majority of them that actually do contribute to disease (often in combination and in complex ways) will never be scientifically associated with disease.  This is because science is far from perfect, scientific methodology is always biased and often manipulated, and scientific interpretation by stakeholders and decision makers is alarmingly inept (I’m not being political or condescending, these are well known and easily observed facts).

The situation with agricultural GMOs is unique compared to other technologies. While genetic engineering of food crops has been ongoing for 15 years, it is currently experiencing a major boom with the potential for widespread worldwide application.  Yet, few people understand how a GMO food could really be so much different than a non-GMO food in regard to health and disease effects.  GMO foods look like non-GMO foods and so we don’t experience the same hesitation and aversion to consuming them like we would, say, a clearly labeled bottle of virus and pesticide in tomato juice.  Therefore, the quality of public education, consumer awareness, and informed public discussion about this technology has the potential to alter the future of GMO agriculture for better or worse.

In this article, I’ll first briefly mention the relative paucity of risk assessment studies on GMOs and the unbelievable weaknesses of the industry studies that have been done.  Then, drawing from numerous independent studies, I will explore the routes by which agricultural GMOs may cause adverse health effects.

GMOs Have Never Been “Proven” Safe

Let me be clear; despite the following negative review of industry science, this article is not a hatchet job against the agricultural GMO industry but, rather, a vehicle for consolidated scientific information on the safety or risks of GMO foods intended to allow readers to make informed choices about this technology.  It is just that, well, the science coming from the industry tends to raise serious concerns and suggests that the agricultural GMO industry has little concern for protecting public and ecosystem health.  Before we dive into the independent non-industry studies which suggest potential harm from GMO crops and foods, we must first look at the studies which supposedly demonstrate the safety of GMO crops and foods.  A critique of these studies remained impossible for some time as the data was kept private, until French researchers obtained a court order for their release.  This team of researchers, lead by Joel Spiroux de Vendomois, then analyzed the raw data from studies on three varieties of GMO corn owned by Monsanto.  Yet, it immediately became apparent that this data was not extremely helpful as the study methodology was profoundly insufficient.  In a 2010 paper published in the International Journal of Biological Sciences[1], the researchers summarize several major flaws in the study.  I’ll list just a few of them here:

1. For each of the three varieties of GMO corn tested, only a single study was done.  However, a central tenet of sound science is that the results are reproducible and replicated by other studies, preferably those done by different researchers.

2. Only the rat was used as a toxicological model.  Rats are useful models for the human detoxification systems, but poor models for human reproductive and embryological systems.  Remember, rat studies “proved” that thalidomide was safe for pregnant women to use… but the rabbit studies done AFTER thousands of babies were harmed “proved” that it caused birth defects!  Scientific proof is only as good as the scientific studies, which are always limited and narrowly focused.

3.  The studies lasted only 3 months and were done on young adult rats.  Yet, captive rats live about 24 months.  No studies looking at late life outcomes from this brief exposure or studies which used lifelong exposure to GMOs were performed.  This is clearly a problem unless human consumers are only supposed to eat GMO foods for no longer than 9 years between the ages of 10 and 20.  Yet, GMO food technology has been released (without labeling) with the intention of lifelong consumption.

4.  No reproductive or developmental studies were done.  Yet GMO foods do not carry a label declaring that their safety during pregnancy has not been evaluated.  Instead, they are unlabeled and meant to be consumed by both genders, at all ages and developmental stages, including during pregnancy and infancy.

5.  Adverse outcomes were only considered if they occurred in both genders!  Clearly genders are different.  For instance, women are much more likely to get breast cancer than men, and one must have a prostate to get prostate cancer.  In the industry studies, increases in prostate cancer in male rats and increases in mammary tumors in female rats would apparently have been omitted since they differed between genders.  This explains exactly what happened to their findings that male rats eating GMO corn had an 11% increase in heart size while female rats eating GMO corn had a 40% increase in serum triglycerides[2].   It is not clear what to make of these findings, but they should not have been omitted and, instead, should have been used to encourage more numerous and longer duration (lifespan) studies before the worldwide release of GMO corn.

6.  Adverse outcomes which are consider “normal” in old rats were omitted in this young rat population.  For instance, the researchers did not consider “chronic progressive nephropathy”, a kidney disease common in older rats, to be a problem even though it was occurring in young, 5 month old, rats eating the GMO corn.

Now, I can attest that modern toxicology students training at respectable universities are taught to do much better work than this. We can only speculate about the reasons such limited study methodologies were chosen.  Nonetheless, these are the studies which the FDA determined to be sufficient for the approval of the three GMO corn varieties represented.  As if the major flaws in the study methodologies were not enough to warrant a different decision, the French team of researchers found a number of concerning associations upon re-analyzing the raw data[3].  They summarize:

“Our analysis clearly reveals for the 3 GMOs new side effects linked with GM maize consumption, which were sex- and often dose-dependent. Effects were mostly associated with the kidney and liver, the dietary detoxifying organs, although different between the 3 GMOs. Other effects were also noticed in the heart, adrenal glands, spleen and hematopoietic system. We conclude that these data highlight signs of hepatorenal toxicity, possibly due to the new pesticides specific to each GM corn.”

This is not the only group of researchers to demonstrate an association between GMO consumption and adverse health outcomes.  Despite the industries resistance to providing GMO varieties to outside researchers for independent studies, there are still dozens of studies available to the public for review.  I’ll synthesize the findings of several of these studies below in considering the possible mechanisms by which agricultural GMOs may cause problems.  In general, the health effects of agricultural GMOs are mediated through at least three routes; 1. Directly though ingestion, 2. Indirectly through GMO associated pesticide exposure and ingestion, and 3. Indirectly through environmental and ecosystem effects.

Effects of GMO ingestion:

Ingesting GMOs can affect both the microbiome and human cells.  The microbiome is the microorganism population which lives on and in the human body.  Most of it exists in or on the mouth, nose, stomach, intestines, and skin.  The gut microbiome has received considerable attention due to its apparently profound effect on the immune system, not to mention its effect on food digestion.  The gut microbiome is involved in determining the risk of autoimmune diseases, allergic diseases, cardiovascular disease, and some infectious diseases like osteomyelitis.  The microbiome can get out of balance (called dysbiosis) and produce severe diseases such as Clostridium difficile overgrowth and more mild disorders like small bowel bacterial overgrowth and irritable bowel syndrome.  The bottom line is that a balanced microbiome is critical for health and we are just now beginning to appreciate how serious the consequences of dysbiosis may be.

Several studies have shown that the organisms (mostly bacteria) of the microbiome can take up genes from GMO foods[4],[5].  “Conjugation”, or gene transfer, is a common trick used by bacteria to evolve and adapt.  This is one mechanism by which antibiotic resistance perpetuates.   The consequences of GMO gene transfer to intestinal bacteria involve the expression of the gene and/or insertional mutagenesis.  The frequency with which these consequences will occur is not known, but they will occur to some degree at least.

Intestinal bacteria which begin to express the GMO gene will then be producing the same active proteins which define the GMO.  For example, intestinal bacteria could start producing the Bacillus thuringiensis (Bt) pesticidal toxin that has been inserted into potatoes, corn, and soybeans.  The exact effect of this toxin on humans, if any, is not well established but it has been found in a study of Canadian women, including pregnant women and their fetuses[6].

Insertional mutagenesis refers to the gene inserting itself into another coding gene and, thus, causing a gene mutation by disrupting the code.  This may produce more severe results as it is a well known mechanism by which viruses may cause cancer, cell death, or cellular dysfunction.

These same mechanisms, gene transfer and insertional mutagenesis, can affect human cells just the same.  While intestinal cells are likely to be the most affected, GMO genes which pass into the blood intact may affect just about any cell and tissue in the body.  It is quite possible that GMO foods are regularly resulting in the genetic modification of the humans consuming them!  There are many unknowns here and I suspect that there remains a lot to be discovered, but we should not let the absence of evidence be mistaken for the evidence of absent harm.  We should, instead, demand more information and more research!

Effects of GMO associated pesticide exposure and ingestion:

Another route of possible harms from GMO foods comes from the exposure to and ingestion of GMO associated pesticides.  The most successful GMO crops have been the “Roundup Ready” or glyphosate resistant varieties of corn, soybean, and cotton.  The same genes have been inserted into alfalfa, wheat, and canola (rapeseed) but these have not yet been widely introduced.  The result of glyphosate resistance is that glyphosate can then be applied without discrimination to area or dose.  In the past, the use of a pesticide like glyphosate to control weeds had to be balanced with the cost of losing crop due to inadvertently heavy crop exposure.  Glyphosate spraying has dramatically increased with the introduction of glyphosate resistant crops.  This logically increases the risk for excessive occupational exposure, the magnitude of environmental contamination with glyphosate, and the direct and indirect exposures to the general public and consumers of GMO foods (including livestock).  Presumably, the glyphosate residue on (and inside… it can’t be washed out) glyphosate resistant food products is higher than that on non-resistant varieties, but data supporting this is scarce.  I’ve failed to find any study which quantifies and contrasts the amount of pesticide residue between GMO and non-GMO foods.  More research is needed, but again we can’t assume that the absence of evidence is evidence of absence.  It is simply unknown if there are any differences, but assuming so is a very logical assumption.

Glyphosate appears to produce a plethora of problems.  Let’s begin with the microbiome again.  Studies have shown that glyphosate may contribute to the contamination of chicken and beef with pathogenic (disease causing) bacteria like E. coli.  The reason is that glyphosate produces a dysbiosis within livestock consisting of the overgrowth of pathogenic bacteria.  It turns out that many of the most dangerous bacterial pathogens are resistant to glyphosate (perhaps due to the gene transfer discussed above), yet some of the most healthy bacteria are quite sensitive to it.  The result is a decline in healthy bacteria and proliferation of pathogenic bacteria.  Glyphosate in chicken feed resulted in the proliferation of salmonella and clostridium species (both of which cause food poisoning and infection in humans) and a decline in enterococcus, bifidobacterium, and lactobacillus (species thought to be the foundation of a healthy microbiome)[7].  Enterococcus and lactobacillus are especially important in preventing the overgrowth of Clostridum botulinum and researchers have suggested, as a result, that glyphosate induced dysbiosis is causing an increase in botulism in cows[8].  The same phenomena has been shown to occur within the human microbiome as well, and it is reasonable to propose that the increasing prevalence of Clostridium difficile dysbiosis, a potentially fatal disorder that is also plagued by increasing antibiotic resistance, may be one of its many consequences.

Beyond the microbiome the situation may be even worse.  It is well known that glyphosate and its metabolites are genotoxic (causing DNA damage), and cytotoxic (causing cell death or dysfunction) to human cells. [9],[10]  Exactly how these toxic attributes manifest as disease is more complex, but the following studies point to several possibilities.

Numerous studies have implicated the pesticides paraquat, rotenone, lindane, and dieldrin in the development of Parkinson’s disease due to their ability to kill dopaminergic neurons, and it appears that glyphosate may have similar capabilities[11].  Several case reports of Parkinson’s disease onset after chronic and acute glyphosate exposure have indeed suggested that glyphosate may contribute to the development of the disease, but more research is needed here[12],[13]. When studied in cultures of nerve cells, however, glyphosate did cause cell death through self-destruction (apoptosis) and self-consumption (autophagy)[14].  Therefore, the biological mechanism behind neurodegenerative diseases like Parkinson’s and Alzheimer’s disease is definitely induced by glyphosate, lending additional credibility to the association.  A recent review article not only associated glyphosate with Parkinson’s disease but also “gastrointestinal disorders, obesity, diabetes, heart disease, depression, autism, infertility, cancer and Alzheimer’s disease”.[15]

Epidemiological studies have suggested an association between chronic glyphosate exposure and certain cancers.  One study, done in Sweden, found that those diagnosed with non-Hodgkin’s Lymphoma were 3.04 times more likely to report a history of glyphosate exposure compared to those without cancer, suggesting that glyphosate may increase the risk of this disease[16].  Another study, using populations in Iowa and North Carolina, suggested a possible association between glyphosate exposure and multiple myeloma[17].

Glyphosate also appears to be a potent endocrine disruptor with pronounced effects on testosterone production in males.  Studies on male rats demonstrate the glyphosate inhibits testosterone related enzymes and decreases the levels of testosterone in a dose-dependent manner[18].   Compared to control rats, those exposed to the highest dose of glyphosate produced only ½ of the testosterone.  Another rat study utilized doses of glyphosate which have been found in samples of human urine (1 ppm) and demonstrated that this dose reduces testosterone production by 35%[19]!  The same study showed that higher doses cause testicular cell death.  A study on human reproductive cell lines demonstrated that endocrine disrupting effects start at a dose of 0.5 ppm.  Genotoxic effects started at a dose of 5 ppm and cytotoxic effects started at 10 ppm[20]. The glyphosate residual that is allowed by federal regulations is 400 ppm in animal feed, 200 ppm in spearmint and peppermint tops, 85 ppm in sunflower and safflower seeds, 30 ppm in barely and cereal grains like rice, 30 ppm in molasses, 20 ppm in soybean, and 5 ppm in corn, legumes and quinoa, just to name a few[21].  Assuming that the average person has 5 liters of blood, one could experience blood levels of glyphosate at 0.5 ppm from eating 125 grams (or roughly 4.4 ounces) of soybeans or 29 grams (1 ounce) of sunflower seeds (note that small bags of sunflower seeds are often 5 ounces or more).

In addition to glyphosate toxicity, we should be concerned about possible toxicity from other GMO associated pesticides like Bt (bacillus thuringiensis) toxin.  The effects of ingesting this GMO crop produced pesticide have hardly been studied.  I found only one study, an in vitro study on human cells, and the results indicate the Bt toxins Cry1Ab and Cry1Ac do trigger cell death at moderate concentrations[22].  Additionally, these pesticides appear to interact with glyphosate (which often accompanies them on food) with unpredictable consequences.

The issue of interaction effects in toxicology is a very serious one that is poorly studied or not studied at all.  Of 80,000 chemicals in production, very few have been studied in combination, let alone the extremely common combinations that are found in the environment and in various products.  For instance, glyphosate is rarely used alone, yet studies still evaluate its toxicity alone.  Glyphosate products contain adjuvants or surfactants that enhance its herbicidal activity.  One study did, in fact, look at the effects of glyphosate and its adjuvants (like POE-15) on human cell lines.  The results showed that the combination was much more toxic than glyphosate alone[23]!

It needs to be mentioned that the levels of glyphosate exposure from food and the complexity and doses of pesticide combinations (and their interactions) are likely to increase as a result of progressing glyphosate resistance.  Just like antibiotic resistance among pathogenic bacteria, the target plants (i.e. weeds) for glyphosate are rapidly evolving a resistance to the pesticide as a result of its intensive use[24].  In order for glyphosate to work on these plants, higher and higher doses are needed, or additional pesticides must be applied simultaneously. Currently there are 24 weed species listed with resistance to glycine pesticides, the pesticide class of glyphosate[25].

To be fair, internal studies done by Monsanto (the owner and producer of glyphosate) in the early 1980’s show glyphosate to be relatively non-toxic.  These are the studies submitted to regulatory agencies for approval and then used to set regulatory limits on public exposure and environmental contamination.  For example, the EPA uses this 30 year old data for its Integrated Risk Assessment System (IRIS).  These reviews often take 10-20 years to complete due to inadequate EPA funding, making them outdated the moment they are published!  Again, no one is out there protecting our health.  You can browse the EPA glyphosate review here if interested: http://www.epa.gov/iris/subst/0057.htm

Environmental and ecosystem effects of agricultural GMOs:

In addition to the possible harm of GMOs and GMO associated pesticides on the microbiome, cells, and physiology of humans and other mammals, there is concern about environmental effects (which always end up affecting the health of the environment’s inhabitants as well). These environmental effects involve the same or similar mechanisms as those above.  For example, GMO genes can transfer to environmental (soil and aquatic) microorganisms as well as native plants (like grasses) and possibly other food crops (like organic corn and soy, the fields of which may become contaminated with GMO seeds)[26].

Additionally, GMO associated pesticides or toxins may negatively impact helpful insects (like predator or carnivorous arthropods) as well as target insects, selecting for the emergence or immigration of new, more resistant, pests[27].  Similarly, intensive use of glyphosate may kill plants which support critical pollinators.  For instance, glyphosate use has reached levels which are now killing milkweed, thus jeopordizing the monarch butterfly habitat and leading to a decline in their numbers.

Additionally, glyphosate and Bt toxin accumulate in the soil due to serial applications, leading to escalations in soil contamination, and glyphosate has been shown to contaminate most agricultural watersheds[28],[29].

The environmental effects of GMOs and GMO associated pesticides have barely been studied and the consequent effects on biodiversity and groundwater (drinking water) are uncertain.

Don’t Throw the Bathwater Out With The Bathwater

To be fair, I need to mention the supposed intentions behind GMO agriculture promoted by the industry.  Clearly, there is a profit motive as there exists a powerful synergistic feedback cycle in the consumption of proprietary pesticides and proprietary pesticide resistant seeds.  However, GMO advocates sincerely, I believe, also hope that the technology can do good in the world.

For instance, “Golden Rice” is genetically modified rice which possesses the genes to produce beta-carotene.  Beta-carotene is the precursor to vitamin A in humans, and in regions of Africa and Asia, vitamin A deficiency is extremely common (causing a number of severe problems such as blindness).   Therefore, this rice could effectively reverse the epidemic of vitamin A deficiency.  Such medical and public health applications of GMO technology do appear to be much more reasonable than the pesticide resistant varieties (which are largely admired because they make agriculture more simple).  However, the potential health implications of medical or public health oriented GMO technology are largely the same as all other GMO technology with regard to gene transfer and insertional mutagenesis.

Even more relevant, however, is that the vitamin A deficiency in much of the world can be remedied in several other ways, many of which will have additional health benefits than just supplying beta-carotene.  The vitamin A deficiency in much of the world is a result of a subsidized grain (largely rice) diet, which is a product of World Bank, World Trade Organization, and UN economic incentives and agreements aimed at increasing the economic output of developing nations.  If the people of these nations were growing food for themselves and not for export, they would likely grow more diverse plant foods.  Beta-carotene is widely abundant in the plant kingdom.  Basically any plant food with a yellow, red, orange, and dark green color is likely to contain significant amounts of beta-carotene.  Essentially, rice is not the solution to the vitamin A deficiency, it is the cause of it.  This is a larger problem and a more difficult one to reverse, for sure, but we need to recognize the difference between real solutions which address the root problem and superficial solutions which simply compensate for one consequence of the problem.  Failure to do so will accelerate our decline down the slippery slope of unintended consequences.

About the Author

Nathan is a visionary in health-oriented medicine, integrative preventive medicine, and ecological medicine. He helps individuals discover their unique paths to health through adventuresome vacations. See: http://ecoholos.com/ and http://www.epichealthexperience.com

Resources:

For additional research on GMOs on the GreenMedInfo.com database: Health Guide: GMO Research