08
Mar
Study Raises Ecological Concerns about EPA-Approved RNAi Pesticides that Turn Off Genes
(Beyond Pesticides, March 8, 2019) Researchers from the U.S. and Switzerland have published their findings, a beginning assessment of how use of a new category of pesticides — dsRNA (double stranded RNA), which is less a traditional pesticide than a genetically based pesticide “technology” — might impact soils and non-target microorganisms in the soil. The co-authors (Kimberly M. Parker, PhD, et al.) note that, “The ecological risk assessment of these emerging pesticides necessitates an understanding of the fate of dsRNA molecules in receiving environments, among which agricultural soils are most important.” Their research appeared in late January 2019 in Environmental Science & Technology.
Previously, technical hurdles in measuring dsRNA had stymied scientists’ ability to quantify the genetic material and its degradation products in soil, but these investigators were able to attach a radioactive atom to the molecule, “tagging” it so it could be followed through a series of simulated soil systems representative of those in the “real” world. Researchers were able to measure the presence of the material at concentrations as low as a few nanograms of dsRNA per gram of soil. The work of these researchers represents the beginning of understanding the ecological risks of these emerging dsRNA pesticides.
They demonstrated that dsRNA molecules in soil suspensions “undergo adsorption to soil particle surfaces, degradation in solution, and potential uptake by soil microorganisms.” In addition, they found that in some soils, enzymes can degrade, or break down, the pesticide, and that some organisms actually “eat” the pesticide and the post-enzymatic fragments. One hypothesis the scientists are considering is that the soil particles may actually be protective of the molecules by slowing down their degradation, and that this effect may be more pronounced in finer, rather than coarser, soils.
How do these dsRNA pesticides work? They impede the expression of essential proteins in target pest insects via a cellular mechanism called RNA interference (RNAi). In RNAi, long dsRNA is “sliced” into small fragments, which then bind to “Argonaute” proteins. When that happens, one of the double strands of the dsRNA is removed, leaving the remaining strand available to bind to messenger RNA targets. Once bound, the Argonaute protein can cleave the messenger RNA, destroy it, or recruit other factors to regulate the target sequence in other ways. The target organism is left either stunted or dead. RNAi is widely used by researchers to silence genes in order to learn something about their function.
In the biochemical genetic engineering (GE) sector, it is hoped that such “gene silencing” technology can be engineered into plants so that they can, functionally, produce their own pesticides. The Environmental Protection Agency (EPA) registered the first four products using dsRNA technology in the summer of 2017. These products were developed in large part to help farmers control corn rootworm, a pest that has developed resistance to several other pesticides. When the rootworm ingests the dsRNA in the corn plant’s tissue, a gene in the insect called Snf7, which is essential for rootworm survival, gets turned off. The first expected commercial product will be a line of GE corn seeds called SmartStax Pro, which will contain both Bt (Bacillus thuringiensis, a bacterium that is toxic to some pests) and a dsRNA called DvSnf7; it is expected to show up on the market by 2019 or 2020. This “stacking” of pesticide technologies by the agrochemical and agrogenetic industries is increasingly common, as they attempt to tackle issues of resistance to chemical pesticides by pairing them with GE approaches — even in the same product, as with the coming SmartStax Pro.
Mamta and M.V. Rajam wrote, in that same summer of 2017 in the journal Physiology and Molecular Biology of Plants, about this new approach to pest control. The authors generally touted the potential of this new GE approach — RNAi silencing, saying that the “ideal pest control strategy . . . should be specific in its action and should target [a] large number of pests without affecting non-targeted organisms.” However, they also identified that “off-target effect is one of the major limitations associated [with] RNAi technology. Off-target effects are describe[d] as the silencing of non-target genes in the same organism or in non-target organisms.
The Atlantic magazine’s 2017 coverage of this emerging technology, by Sarah Zhang, noted that RNAi is considered useful because of its specificity: it can turn off one gene in one species while, theoretically, leaving others unaffected. Organisms use this “gene silencing” on their own all the time. Scientists have created genetically modified crops, such as those grown from Monsanto’s Roundup Ready soy, corn, and alfalfa seeds, and industry scientists have previously used RNAi to create GE crops (such as apples and potatoes that do not brown because their browning gene is silenced). The difference in the case of this emerging technology, to be launched in Dow’s (formerly Monsanto’s) DvSnf7 dsRNA product, is that it silences a gene in another living organism. Ms. Zhang says: “Rather than modifying itself, it modifies its environment.”
Among the concerns about this dsRNA/RNAi pesticide technology becoming “operational” in plants are hazards identified in an article in the August 2013 issue of the journal BioScience, by Jonathan G. Lundgren and Jian J. Duan. The authors acknowledge that “the creation of RNAi-based GM [genetically modified] crops that are lethal to pests or that deleteriously affect interactions of the pests with other organisms (including the crop) is a very real technology that has potential for limiting the impact of pests on crops.” They note that for “traditional” chemical and microbial pesticides and Bt crops, the modes of action are reasonably well understood, and that “laboratory nontarget toxicity assays can be focused and optimized on the basis of predictable effects.” They contrast that with assessing nontarget toxicity for RNAi pesticide technology, which produces those small “bits” of genetic material (small RNAs) from the source dsRNA: “Small RNAs often have off-target binding elsewhere in a nontarget species’ genome that makes predicting toxic effects and designing maximum-hazard dose assays challenging for the wide range of species potentially exposed.”
The authors further note that when these small RNAs, or siRNAs (small interfering RNAs) silence unintended (nontarget) genes, the hazards include: “off-target gene silencing, silencing the target gene in nontarget organisms, immune stimulation, and saturation of the RNAi machinery,” and that, “Knowledge gaps in the genomics and physiologies of highly exposed nontarget organisms currently preclude our ability to assess the activity spectrum of RNAi, determine whether toxicity assays will be sufficient in predicting the risks of RNAi-based crops, and explain how these risks may affect food webs associated with agroecosystems.” An additional unknown is how persistent siRNAs may be in the environment.
Adding to concern is the fact that, unlike traditional pesticides, which pose no risk to nontarget organisms if there is no physical or physiologic exposure to these toxicants in the environment, this GE technology represents unknown levels of potential exposure. If the technology is broadly adopted, the scale of the “unknown” is truly daunting, given the amount of land in the U.S. that is planted in corn, never mind its potential use in other commodity crops (soybeans, cotton, e.g.). Further, there is little-to-nothing yet understood about effects on ecosystems where this technology could be deployed, or effects on people (or other animals) after specific dsRNA/RNAi is ingested dietarily.
The subject study is a beginning look at the interaction of this GE pesticide technology in soils, but there are huge gaps in understanding about the organismic and environmental implications of this GE “pesticide.” One of the authors, Dr. Parker says, “Now that we have identified the major processes controlling pesticide degradation in soils, we will next investigate in detail the variables that control these processes to enable accurate ecological risk assessment of double-strand RNA pesticides. This will allow us to understand whether or not these new pesticides pose a risk to ecosystems.”
Beyond Pesticides wrote about RNAi technology back in 2015, when the GE (via RNAi) Arctic apple was on the horizon. It noted at that time that, as always, GE crops can represent threats to organic food production through cross-contamination, usually via bee pollen. Keep current on developments on this emerging GE pesticide technology via the Beyond Pesticides Daily News Blog, which tracks developments in research, policy making, and advocacy.
All unattributed positions and opinions in this piece are those of Beyond Pesticides.
