by Megan L. Norris

Summary: As the prevalence of genetically modified organisms (GMOs) continues to rise, there has been an increasing public interest for information concerning the safety of these products. Concerns generally focus on how the GMO may affect the environment or how it may affect the consumer. One specific concern is the possibility for GMOs to negatively affect human health. This could result from differences in nutritional content, allergic response, or undesired side effects such as toxicity, organ damage, or gene transfer. To address these concerns, there have been over 100 research studies comparing the effects of traditional food to genetically modified food, the results of which have been reviewed in various journals [1], [2]. How these results affect regulation can be found through The Center for Environmental Risk Assessment, which hosts a GM Crop Database that can be searched by the public to find GMO crop history, style of modification, and regulation across the world [3]. Though knowing who to trust and what to believe regarding this topic is an ongoing battle, major health groups, including the American Medical Association and World Health Organization, have concluded from the research of independent groups worldwide that genetically modified foods are safe for consumers [4]. Regarding toxicity, this includes any dangers related to organ health, mutations, pregnancy and offspring, and potential for transfer of genes to the consumer.

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GMO toxicity: fears and scientific analysis

After genetically modified foods were introduced in the United States a few decades ago, people independently reported toxic effects caused by GMOs. One example is an anti-GMO advocacy group called the Institute for Responsible Technology (IRT), which reported that rats fed a diet containing a GMO potato had virtually every organ system adversely affected after just ten days of feeding [5]. The IRT stated that the toxicity was the result of genetic modification techniques and not a specific case for that particular potato. They claimed the process of making the GMO caused it to be toxic and thus all GMOs were high risk for toxicity.

Scientists across the U.S. and the rest of the world have sought to rigorously test the assertions of the IRT and others to uncover any possible toxicity caused by GMOs. To this end, many different types of modifications in various crops have been tested, and the studies have found no evidence that GMOs cause organ toxicity or other adverse health effects. An example of this research is a study carried out on a type of GMO potato that was genetically modified to contain the bar gene. The product of the bar gene is an enzyme that can detoxify herbicides and thus protects the potato from herbicidal treatment.

In order to see if this GMO potato would have adverse effects on consumer health like those claimed by the IRT, a group of scientists at the National Institute of Toxicological Research in Seoul, Korea fed rats diets containing either GMO potato or non-GMO potato [6]. For each diet, they tracked male and female rats. To carefully analyze the rats’ health, a histopathological examination of tissues and organs was conducted after the rats died. Histopathology is the examination of organs for disease at the microscopic level (think pathologist doing a biopsy). Histopathological examinations of the reproductive organs, liver, kidneys, and spleen showed no differences between GMO-eating and non-GMO-eating animals.

Three years earlier, a separate group had found the same results for a GMO tomato and a GMO sweet pepper [7]. These researchers had split rats into four diet groups: non-GMO tomato, GMO tomato, non-GMO sweet pepper, and GMO sweet pepper. They fed the rats over 7,000 times the average human daily consumption of either GMO or non-GMO tomato or sweet pepper for 30 days and monitored their overall health. Finally, they carried out histopathology and again found no differences in the stomach, liver, heart, kidney, spleen, or reproductive organs of GMO versus non-GMO fed rats. Despite massive ingestion of GMO potato, tomato, or sweet pepper, these studies demonstrated no differences in the vitality or health of the animals, even at the microscopic level.

Experiments like these on humans would be completely unethical. Fortunately, prior to these studies years of work have demonstrated that rodents, like mice and rats, are acceptable models for humans, meaning rodent responses to drugs, chemicals, and foods can predict human response. Rat feeding studies like these, in which rats are fed a potential toxic item and monitored for adverse effects, are considered both specific and sensitive for monitoring toxicity of foods and widely used in the food regulation industry [1].

The test of time: GMOs and their effect on our offspring

Although scientists have been able to demonstrate that GMOs are not toxic to the animals that eat them, as described above and elsewhere, what about side effects being passed on to our next generations?

To discern whether GMO crops affect fertility or embryos during gestation, a group from South Dakota State University again turned to studies on rats. In this case, the rats were eating a type of GMO corn, more commonly known as Bt corn. Bt stands for Bacillus thuringiensis, a microbe that produces insecticidal endotoxin and has been used as a topical pesticide against insects since 1961 (see this article). To allow corn to directly generate this endotoxin, scientists introduced a gene from Bt into the genetic material (DNA) of corn.

To address buildup of toxicity over time, this group monitored the GMO-eating rats not only for the lifetime of one generation, but also three additional generations. For each generation, they tracked the fertility of parents and compared the health of the embryos from parents that ate Bt corn to those with parents that did not [8]. Toxic effects can arise in many places and in many ways, but some organs are more susceptible to damage than others, and monitoring them is a good readout for other difficult-to-see effects. Testes are considered a particularly sensitive organ for toxicity tests because of the high degree of cell divisions and thus high susceptibility to cellular or molecular toxins.  To examine the affect of Bt corn on testicular health, the researchers tracked testicular development in fetal, postnatal, pubertal, and adult rats for all four generations. The group found no change in testicular health or litter sizes in any generation. Likewise, ingestion by pregnant mothers had no effect on fetal, postnatal, pubertal, or adult testicular development of her offspring.

Other groups have monitored toxicity over time as well. For example, the group studying the bar GMO potato also wanted to see if organs and reproductive health were sensitive to GMOs over long exposure times [5]. To do this, they examined the fertility and gestation periods of GMO-eating mothers compared to non-GMO-eating mothers for five generations. They tracked animal body weight, bone, eye, and thymus development, and general retardation. Like the studies on Bt corn, in all cases, they found no significant differences between the GMO potato and non-GMO potato diets, suggesting that there is no buildup or inheritance of toxicity, even over multiple generations.

Figure 1. Work from independent researchers has investigated various aspects of GMO safety, especially concerning consumer health and toxicity.

Can GMOs change our genes?

Concern has also surrounded the idea that genetically modified DNA would be unstable, causing damage (via unintentional mutations) not only to the crop, but also to whomever would consume it. Mutations in DNA are closely tied to cancer and other diseases, and thus mutagenic substances can have dire effects on human health. The creation of mutations, called mutagenesis, can be measured and compared to known mutation-causing agents and known safe compounds, allowing researchers to determine whether drugs, chemicals, and foods cause increased mutation rates. There are a variety of ways to measure mutagenicity, but the most traditional method is a process pioneered by Bruce Ames at the University of California in Berkeley. His method, now called the Ames test in his honor, is able to track increased rates of mutations in a living thing in response to some substance, like a chemical or food.

To directly test the ability of a GMO to cause mutations, a research group from the National Laboratory of Protein Engineering and Plant Genetic Engineering in Beijing, China applied the Ames test to GMO tomatoes and GMO corn [8]. GMO tomatoes and corn express the viral coat protein of cucumber mosaic virus (CMV). Expression of this coat protein confers resistance to CMV, which is the most broadly infectious virus of any known plant virus, thought to infect over 1,200 plant species from vegetable crops to ornamentals. The results of the Ames test demonstrated no relationship between GMO tomatoes or corn and mutations. They repeated their analysis using two additional methods for analyzing mutagenicity in mice and got the same result, allowing them to conclude that genetically modified DNA did not cause increased mutations in consumers. The modified DNA, like unmodified DNA, was not mutagenic.

Mutagenicity aside, there are also concerns surrounding the ability of the modified DNA to transfer to the DNA of whomever eats it or have other toxic side effects. Depending on the degree of processing of their foods, a given person will ingest between 0.1 and 1 g of DNA each day [9]; as such, DNA itself is regarded as safe by the FDA [10]. To determine if the DNA from GMO crops is as safe to consume as the DNA from traditional food sources, the International Life Sciences Institute reviewed the chemical characteristics, susceptibility to degradation, metabolic fate and allergenicity of GMO-DNA and found that, in all cases, GMO-DNA was completely indistinguishable from traditional DNA, and thus is no more likely to transfer to or be toxic to a human [9]. Consistent with this, the researchers working on the GMO potato attempted to isolate the bar gene from their GMO eating rats. Despite 5 generations of exposure to and ingestion of the GMO, the researchers were unable to detect the gene in the rats’ DNA [5].

A strong argument for GMO health safety

After more than 20 years of monitoring by countries and researchers around the world, many of the suspicions surrounding the effects of GMOs on organ health, our offspring, and our DNA have been addressed and tested (Figure 1). In the data discussed above, alongside many more studies not mentioned here, GMOs have been found to exhibit no toxicity, in one generation or across many. Though each new product will require careful analysis and assessment of safety, it appears that GMOs as a class are no more likely to be harmful than traditionally bred and grown food sources.

Megan L. Norris is a Ph.D. candidate in the Molecular, Cellular and Organismal Biology Program at Harvard University.

This article is part of the August 2015 Special Edition, Genetically Modified Organisms and Our Food.

References

1. European Food Safety Authority GMO Panel Working Group on Animal Feeding Trials. “Safety and nutritional assessment of GM plants and derived food and feed: the role of animal feeding trials.,” Food Chem. Toxicol., vol. 46 Suppl 1, pp. S2–70, Mar. 2008
2. G. Flachowsky, A. Chesson, and K. Aulrich, “Animal nutrition with feeds from genetically modified plants.,” Arch. Anim. Nutr., vol. 59, no. 1, pp. 1–40, 2005.
3. Cera-gmc.org, ‘Welcome to the Center for Environmental Risk Assessment | CERA’, 2015. [Online]. [Accessed: 11- Jul- 2015].
4. Tamar Haspel. “Genetically modified foods: What is and isn’t true”. Washington Post. October 15, 2013.
5. Jeffrey Smith. “GM Potatoes Damaged Rats.” Genetic Roulette, Section I: Documented Health Risks.
6. G. S. Rhee, D. H. Cho, Y. H. Won, J. H. Seok, S. S. Kim, S. J. Kwack, R. Da Lee, S. Y. Chae, J. W. Kim, B. M. Lee, K. L. Park, and K. S. Choi, “Multigeneration reproductive and developmental toxicity study of bar gene inserted into genetically modified potato on rats.,” J. Toxicol. Environ. Health. A, vol. 68, no. 23–24, pp. 2263–2276, 2005.
7. Z. L. Chen, H. Gu, Y. Li, Y. Su, P. Wu, Z. Jiang, X. Ming, J. Tian, N. Pan, and L. J. Qu, “Safety assessment for genetically modified sweet pepper and tomato,” Toxicology, vol. 188, no. 2–3, pp. 297–307, 2003.
8. D. G. Brake, R. Thaler, and D. P. Evenson, “Evaluation of Bt (Bacillus thuringiensis) Corn on Mouse Testicular Development by Dual Parameter Flow Cytometry,” J. Agric. Food Chem., vol. 52, no. 7, pp. 2097–2102, 2004.
9. D. A. Jonas, I. Elmadfa, K. H. Engel, K. J. Heller, G. Kozianowski, a. König, D. Müller, J. F. Narbonne, W. Wackernagel, and J. Kleiner, “Safety considerations of DNA in food,” Ann. Nutr. Metab., vol. 45, no. 6, pp. 235–254, 2001.
10. FDA: Guidance to Industry for Foods Derived from New Plant Varieties, Section V (C).

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