The Solution to a Future of Dietary Downfall, Biopharmaceutical Demands, and Climate Change Genetic manipulation of crops is not new – not in the 20th century, and certainly not in the 21st. Rather, the practice has roots dating back to the invention of agriculture. For thousands of years, humans have been harnessing the natural variability in the plant genome via selective breeding, which involves crossing plants with particular characteristics to emphasize desired phenotypic traits in future generations. Early farmers dating back to 11,000 B.C. unconsciously selected plants with superior traits albeit the lack of genetics knowledge, leading to improved yield, pest resistance, and tolerance to drought stress (as reviewed in Pachter and Puchta, 2016).
While selective breeding is not typically classified as genetic modification technology, as defined nowadays, it is the earliest example of humans influencing the genetics of plant species and serves as a precursor to the modern methods of genetic engineering: transgenesis and genetic editing. Modern genetic engineering uses the same underlying principles as selective breeding, but expands the breadth through a wider range of technological options and the ability to introduce genes from various species. In a breakthrough that would ultimately redefine the limits of plant contributions to society, Stanley Cohen and Herbert Boyer successfully engineered the first genetically engineered organism by transferring a gene coding for antibiotic resistance from one strain of bacteria into another. Cohen and Boyer’s work laid the foundations of recombinant DNA technology, however it wasn’t until 1994 that the advancements in GMO technology reached the attention and accessibility of the general public.
The FlavrSavr tomato, genetically engineering to have longer shelf-life, was the first GMO to reach mainstream consumer markets (as reviewed in Kramkowska et al., 2013). It was this introduction of GM crops into direct reach of the general public that sparked a controversial debate over the safety of genetically engineered crops with respect to the health, biodiversity, and the environment. A complex scientific and political debate continues to stir between environmental conservationists, biologists, politicians, and epidemiologists regarding the environmental, ecological, and health effects of GMOs at large. This leads to the central question: should genetically modified crops be banned in the United States? Based on the scientific evidence, the answer is no. Genetically modified crops have consistently shown through various studies to improve the nutritional quality of food, have potential to revolutionize the biopharmaceutical industry with cheaper and easy-to-administer drugs, and armor the United States in its future battle against climate change.
Genetically modified crops have the ability to improve the food situation worldwide, both in terms of quantity and quality. One hundred Nobel laureates came to the consensus that in order to feed to world’s exploding population, the sole option is to engage in genetically modified food cultivation and production (as reviewed in Tsatsakis et al., 2017). In order to address the central question and direct the research more towards the demographics of the United States, there is extensive research supporting the role of genetically modified food in improving the nutritional quality of food by changing the composition of lipids, carbohydrates, and proteins in plants. Genetically modified plants have been engineered to be highly concentrated sources of important nutraceutics, such as vitamins A, C, and E, unsaturated fatty acids, probiotics, among many more (as reviewed in Kramkowska et al., 2013).
Among these, the potential for genetically modified plants, as a means of improving fatty acid composition seems the most relevant and beneficial for the United States population. In the United States, the number one disease in terms of number of fatalities and in total cost of treatment is cardiovascular disease, a lifestyle disease to which an unhealthy diet is a contributing factor. In 2009, the total expenditure for treating patients with cardiovascular disease was $475.3 billion US dollars (Kockaya and Wertheimer, 2010). Based on these statistics, it is reasonable to place cardiovascular disease as a high priority target for further intervention and alleviation research. One line of such research focuses on the role of oleic acid in helping prevent lifestyle disease, such as cardiovascular disease (as reviewed in Huertas-Lopez, 2010).
In one study, researchers produced rice brain oil with high oleic acid//low linoleic rice content by disrupting the OsFAD2-1 gene by CRISPR/Cas9-mediated targeted mutagenesis. The CRISPR/Cas9 plasmid vector used to knock out the OsFAD2-1 gene was transformed into rice via Agrobacterium. Fatty acid desaturase 2 (FAD2) normally catalyzes the conversion of oleic acid to linoleic acid, thus the knockout method enabled the production of a genetically modified high oleic/low linoleic acid rice. The results were successful, increasing the oleic acid two-fold and decreasing the linoleic acid to undetectable levels (Abe et al., 2018). The potential to considerably improve the fatty acid composition of foods can lower the risk of lifestyle diseases, such as cardiovascular disease.
In addition to engineering oil that has improved fatty acid concentration, researchers have also demonstrated successful transgenesis events to increase the concentration of dietary carotenoids, in particular astaxanthan. Astaxanthan plays an important role in boosting the immune system and also reducing risk of DNA damage. In one study, researchers co-expressed algal β-carotene ketolase from Chlamydomonas reinhardtii and β-carotene hydroxylase from Haematococcus pluvialis in tomatoes in order to convert β-carotene to astaxanthan. The results showed a 16-fold increase in total carotenoid capacity in the tomatoes without affecting normal plant growth and development (Huang et al., 2013). The ability for researchers to genetically engineer rice bran oil with healthier fatty acid composition and tomatoes with more concentrated dietary carotenoids showcases the potential for improving the nutritional quality of foods, which can have downstream effects on decreasing the incidence and severity of disease inflicting humans.
In the United States and throughout the world, plants can act as “green factories” for biological building blocks such as proteins, lipids, and carbohydrates with improved nutritional value. Not only do genetically modified crops have the potential to improve the health of humans through diet, but also through medications. Currently in the United States, the demand of biopharmaceuticals is on the rise, yet the expense of biopharmaceuticals limits their availability and accessibility to those who need them. Plant-derived biopharmaceuticals provide the benefits of cheap production, easy storage, and safer than those derived from animals (as reviewed in Daniell, 2001).
One example of modifying plant varieties for synthesis of biologically active compounds includes a study involving the expression of oleosin-human insulin (OB-hIN) in transgenic Arabidopsis thaliana. The insulin derived from the transgenic plants was tested for its biological activity both in vivo in an insulin tolerance test in mice as well as in vitro in a phosphorylation assay performed in a mammalian cell culture system. Results indicated that 0.13% of the total seed protein was insulin and generated the predicted product. This promising study is especially relevant in industrialized countries such as the United States, where Type I diabetes is the third largest cause of death after cardiovascular disease and cancer (Nykiforuk et al., 2006).
With an increasing incidence of diabetes and increased demand for affordable insulin, “pharming” (using genetically modified plants for biopharmaceutical purposes) supplements the previously described nutritional improvements in enhancing the health of the United States population. Less related to diet but nonetheless still extremely relevant in the population, researchers have also investigated the potential for transgenic plants as a mean of immunotherapy for pollinosis. In the United States, allergic conjunctivitis induced by ragweed pollen or birch pollen is common. Currently, the primary treatment for allergic conjunctivitis is antiallergic eye drops containing antihistamines.
However, this treatment only provides temporary relief. Scientists are seeking a means to delivery oral immunotherapy, a solution that would both be convenient and improve compliance. In a study conducted, transgenic rice seeds expressing antigens from pollen and dust mites in mice successfully suppressed allergic conjunctivitis in mice. The mice fed the transgenic rice for three weeks exhibited less sneeze frequency and less nasal lavage fluid (Fukuda et al., 2018). In addition to insulin and immunotherapy against allergies, there is research surrounding transgenic plants and edible plant vaccines in which antigens have directly been transferred into the plant cell’s nucleus or chloroplast. With further research, this idea could dramatically decrease the cost of vaccines, as immunogenic proteins of major pathogens can be synthesized in plant tissue, orally administered and edible, and would not need to undergo the expensive purification process (as reviewed in Daniell, 2001).
Smaller dosages of plant vaccines would also be needed because the plant cell wall makes it more resistant against digestive enzymes in the gut (as reviewed in Fukuda et al., 2018). The fusion of the biopharmaceutical industry with cutting edge genetic modification techniques provides the potential for alleviating human diseases and the cost of treatments. In addition to directly enhancing human health through improving the nutritional quality of food products and providing biopharmaceutical products, genetically engineered crops can also indirectly prepare humans for the future of Earth with climate change. By 2050, atmospheric [CO2] is expected to increase from 400 to 550 micromol/mol-1 and a temperature increase of 1-6°C (compared to 1990) is expected. Under such conditions, crop productivity would have to increase by 60-110% over 2005 levels by 2050 (as reviewed by Kohler et al., 2016).
In a study conducted, researchers transformed soybean (Glycine max) with the cyanobacterial gene FBP1 using an Agrobacterium-mediated method. The researchers tested how expression of the FBPase/SBPase bifunctional enzyme affects carbon assimilation and seed yield in soybeans. For three growing seasons, wild type and the transgenic plants were grown in fields under in ambient versus elevated CO2 and temperature conditions. At the conclusion of the study, the transgenic soybean plants had significantly higher carbon assimilation and maintained seed yield levels, while the wild type’s seed yield showed 11-22% reductions. Since FBPase and SBPase are involved in C3 photosynthesis, researchers concluded that manipulating the photosynthetic carbon reduction cycle through genetic modification can help plants tolerate the impending CO2 and heat dress with the climate change (Kohler at al., 2016).
Showing consistency among the results, a similar study also showed the efficacy of transgenic crops is surviving and thriving in the stressors present by climate change. On the contrary to the previous study, this one examines crop stress resistance using multiple genes. Five stress resistance genes (NCED3, ABAR, CBF3, LOS5, and ICE1) from Agrobacterium strain COR308 were transferred to rapeseed (Brassica napus L. ), an important oil crop. In response to the abiotic stresses of high temperature, low temperature, and drought stress, the multi-gene transgenic exhibited increased growth compared to the wild types in both the normal and stress conditions. The transgenic plants had higher leaf temperature, lower stomatal aperture, and lower water loss rates compared to the wild type plants. One important measure was RFW, the relative fresh weight, calculated by fresh weight of stressed seedlings/fresh weight of non-stressed seedlings. Compared to WT, the transgenic crops showed statistically significant greater RFW, increased water holding capacity, and more biomass accumulation (Wang at el., 2018).
Thus these studies consistently showed that transgenesis of plants can help armor us in preparation for the change in climate. With the studies and rationale presented, it is a well-supported argument that genetically modified crops in the United States should not be banned. Through the use of food and pharmaceutical products derived from transgenic and gene-edited crops, the health of the human population will benefit both through diet and through supplements. The food and products derived form transgenic crops that reach consumers undergo rigorous testing. Some of the tested factors include traits of parental organism, source, expression products of genes used for medication, new properties of the transgenic organisms, effect of GMOs on living bodies, etc (as reviewed in Kramkowska et al., 2010).
