by Caitlin Smith
Genetically modified organisms (GMOs) seem like a great idea at first—just use recombinant DNA technology to add or replace a gene with another gene. With such targeted modifications, we could make our food crops resistant to insects, herbicides, and drought. We could make ourselves resistant to cancer, heart disease, and neurodegenerative diseases—right? Unfortunately, it isn’t as simple as we might wish, either technically or ethically. Sorting GMOs from wild-types requires extensive testing and labeling. The potential risks of GMOs are unknown, and we are still debating even how to assess the risks.
Detecting and boosting
Almost anyone who uses GMOs needs to test for the presence of genetic modification (GM) to identify GMOs. Most of these tests are PCR-based, but some also use ELISA or other tests. Two common targets of screening for GMOs are the 35S promoter from the cauliflower mosaic virus, and the NOS terminator from Agrobacterium tumefaciens. With more and more GMO detection kits available commercially, the choice of screening targets will widen.
Gerda Botha, lab manager for GMO Testing at the University of the Free State in South Africa, who uses real-time PCR tests to detect GM, says that the biggest challenge is “risk assessment and safety” for GM crops. “With the advance of nutritional and pharmaceutical crops, new levels of complexity will be added to GMOs, and to say the least, the debate on first generation (current) GM crop safety is still raging,” she says. “The challenge lies in some scientists not addressing risk assessment and safety, some even see it as slowing down technology. GM has a role to play, but if an adverse effect occurs, it cannot be taken back, unless regulations are in place to deal with it. Of course the situation and arguments are far more complex, but if scientists cannot agree on the safety of base-level GM crops, how can secondary generation crops be released?”
Though PCR is the standard method for GMO detection and quantification, David Lee, a research scientist at National Institute of Agricultural Botany (NIAB), has been investigating alternative methods such as “loop-mediated isothermal DNA amplification (LAMP)”. LAMP can amplify GM DNA sequences directly from plant tissues without prior purification of the DNA. Dr Lee has also developed an alternative quantification method that he calls “QUIZ” (quantitation using informative zeros), which applies statistical methods to estimate the numbers of DNA molecules in a sample. It is possible to establish the GMO content of a sample by counting the numbers of GM molecules in relation to a standard genomic target (reference). “QUIZ’s major advantage is that it does not need to use calibration standards to do the quantification required by the industry standard (real-time PCR),” says Lee.
Widening the tool set for crop protection, Syngenta Biotechnology—which commercialized the first GM corn to protect against an insect called European Corn Borers—is adding chemical help to the genetic mix. “[We] work across these traditional product lines to look at what other combinations of offerings can be used with our biotech products,” says Jane Bachmann, Syngenta’s science communications manager. “For example, we may use seed treatment products on corn seeds which are genetically modified. In many cases, our products not only protect against a broad range of insect pests, but also provide herbicide tolerance. Additionally, we use the best germplasm, which often has other yield benefits for our customers—for example, for soybean, the product could have enhanced tolerance against fungus, improved drought tolerance, or an improved nutritional profile through oil content.”
Fighting disease
Scientists are also exploring the use of GMOs to fight diseases such as malaria and dengue fever, which are transmitted by parasite-carrying mosquitoes. The Bill and Melinda Gates Foundation invested about $40 million into genetic plans to stop transmission, as millions of people die each year from malaria alone. If mosquitoes could be genetically modified to be immune to malaria, the cycle of transmission could be broken. One caveat is that the disease-causing parasite that mosquitoes carry has an ability to counter genetic changes in mosquitoes to overcome their immunity. Releasing GM mosquitoes into the environment is also not as easy as it sounds (the first release plans may occur within large netted areas to observe how the GM mosquitoes interact with wild-type ones). Charles Taylor, professor in the department of ecology and evolutionary biology at UCLA, says that “assessing local acceptance and determining criteria for local acceptance is going to be an important issue that needs to receive more attention than it has to date. [Also], more attention should be paid to intermediate steps toward acceptance and release, [such as] extensive computer simulation and analysis of possible side effects.”
Other genetic modifications may hold a bright future for fighting diseases as well. For example, “the use of gene therapy for medicinal purposes is very exciting and challenging,” says Lee. “The ability to ‘repair’ a defective gene [such as in] cystic fibrosis means that the patient would not require life-long drugs.” He also notes the possibility of using GM plants as producers of therapeutic compounds. “The use of plants as biofactories makes sense: disease-free drugs cheaply. The harvesting of specific compounds makes sense commercially and should be energy efficient. All should contribute to a more sustainable future.”
A GMO alternative
While the debate over GMO safety rages on, some researchers are forging alternative methods to accomplish the same ends. For example, Cibus has developed their Rapid Trait Development System (RTDS), which, according to Peter Beetham, Cibus’ senior VP of research, is “an all-natural, environmentally safe ‘smart breeding tool’ that helps farmers grow plants with desireable traits to enhance productivity.” RTDS differs from so-called transgenetic engineering—which inserts genetic material from one species into another—in that genetic traits are derived from within the same species. Beetham explains this process, which they call gene conversion: “Every time a cell copies DNA, it makes ‘scrivener’ errors, or spelling mistakes. These errors happen all the time, which is how natural variation arises. Cibus’ technology harnesses the cell's own natural DNA repair machinery to correct such spelling mistakes, directing DNA repair enzymes to correct and repair the targeted gene in a specific way in order to produce a desired trait. Given its precision, the process is similar to altering a letter in a single word contained within a large book. Nothing in the genome is altered by this approach other than the changes directed by the process, which could also occur in nature.”
Cibus says that RTDS is faster and more precise than traditional methods of making GMOs, thus reaching market faster. For example, crops that are modified with RTDS also benefit from fewer regulations. “RTDS’s crops can go to market directly and will not be subjected to any GMO regulation,” says Beetham. “RTDS has already won USDA approval as a safe, natural technology that poses no threat to consumers or to the environment. With RTDS crops, American farmers will be able to enter the global markets that reject GMO crops and compete in those markets with a commercially viable alternative.”
Unfortunately, RTDS cannot today be applied to safer genetic changes in humans, for instance in genetic therapies for diseases. The genetic organizations of both animal and plant kingdoms face increasing changes in the decades ahead. Having only recently begun to map genomes of whole organisms, now we need to systematically keep tabs on all the alterations to these original maps—and their intended, and unintended, consequences.