Pesticides are critical to grow food, but concerns are widespread. Here’s why they are overblown – and a look at the cutting-edge RNA genetic tools designed to reduce health risks even more

Credit: Getty Images
Credit: Getty Images

For farmers to supply society with food, fiber and fuel they must battle pests. There is no magic, natural way to avoid this issue. The “enemies” include insects, mites, fungi, bacteria, viruses and weeds. Many of these challenges are becoming even more problematic with changes in the climate that extend the overwintering range of some pests and accelerating their life-cycles. 

Unless farmers minimize pest damage, they cannot make responsible use of limiting resources including land, water, energy and labor. To do this they often need to use pesticides, and this is true whether they are organic or conventional producers. Some environmental groups, such as the Environmental Working Group which annually issues a “Dirty Dozen” list of fruits and vegetables they claim are ‘contaminated’ by chemical residues, contend that farmers systematically overuse pesticides, endangering our food supply. 

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Those broad claims are not supported by independent scientists nor by risk assessment data from the US Environmental Protection Agency. Although decades of regulation and innovation have dramatically improved the environmental and health impacts of pesticides, ongoing sustainability and health concerns are prompting innovations. The current modern arsenal of pest control technologies begins with synthetic pesticides, but also includes biological pesticides, beneficial organisms, transgenic (genetic modification) and traditional genetic resistance, and various cultural practices. Progressive farmers deploy these “weapons” within an integrated pest management (IPM) control framework. Even so, there is always room for improvement.

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The push for new and ever more exacting tools has spurred considerable interest in an emerging pesticide technology based on RNA that could take sustainable agricultural pest management to the next level. There are three dimensions to this potential: 

  • Precision — Extremely precise targeting of a pest species without any impact on other organisms, particularly those that are beneficial for the crop 
  • New “modes of action” — something that is urgently needed to deal with the problem of pests becoming resistant to existing control products, and
  • Barrier Reduction — A faster and less expensive pathway to new product development, particularly in comparison to the hurdles for any new synthetic pesticides or transgenic pest resistant crops

‘Precision’ has emerged as a general trend across agriculture today as farmers now have the tools to plant different seed varieties and apply fertilizers at variable rates in different parts of a field. Farmers can now make those decisions based on “big data” about the current status of the crop and historical record of each subsection of those fields. 

upes agritech

Classic broad-spectrum insecticides like organophosphates have been largely replaced with more targeted options that are designed to be active against only one order of insects such as beetles, caterpillars, or flies. Old ‘multi-site’ fungicides like copper sulfate or Captan also have increasingly been replaced by more targeted innovations, products with specific modes of action which might only effect one class of fungal pests like rusts or “water molds.”  

Even with these advances, there are often situations in which effective control of one pest will have unintended consequences for beneficial organisms that might otherwise have kept the population of some other pest under control. 

This new product category is based on RNA – the natural chemical class that exists in every living cell which serves as the translator between the genetic code of DNA and the proteins specified by those genes. Because the technology taps into the extreme specificity of genes, it can be used to develop very precise pesticides that might only effect one pest species without having any negative impact on beneficial organisms.

Here’s how it works: The new pesticides are relatively short segments of double stranded RNA (dsRNA), which has emerged in recent years as an appealing alternative to induce pest resistance in genetically modified crops. Segments of dsRNA are chosen to correspond to part of the sequence of a gene for some key enzyme or other protein in the pest. There is a nearly universal mechanism within living cells that recognizes double stranded RNA as a virus threat and effectively puts up a “wanted poster” for that specific sequence. 

Courtesy: CropLife

In cells that poster enlists a system that degrades any single-stranded RNA that has the target sequence. So, when one of these RNA pesticides get inside of a pest, that organism’s own version of the antiviral mechanism greatly diminishes the amount of the regular single-stranded RNA needed to drive production of the targeted enzyme with the effect of disabling or killing the pest. 

By carefully choosing the sequence used in the dsRNA it is possible to avoid any effects on non-target species, particularly those that might be beneficial such as pollinators or predators and parasites of other pests. This feature would definitely enhance IPM programs that seek to foster beneficials.

The first likely EPA-registered example of a double-stranded RNA product is one that has been designed to control the Colorado potato beetle (CPB) — a major pest of that staple crop. It was developed by a company called Greenlight Biosciences. CPB is known as a “super pest” because it is already very challenging to control and climate change is allowing it to go through even more generations each year.

The grub stage of Colorado Potato Beetles destroying potato leaves

CPB is also good at developing resistance against almost any insecticide when it is used exclusively, so farmers need to rotate from spray to spray by rotating products with different “modes of action”. This new product could provide farmers a completely new and much needed mode of action. 

Many of the existing pesticides used to control CPB can lower the populations of predators and parasitoids of a different pest called the green peach aphid, and so sprays for CPB can cause populations that aphid to flare to damaging levels. Because of the precise targeting feature of RNA-based products, this new option will be safe for those “beneficials” so they can keep the aphid populations in check.

Impact on health-challenged bees

Another one of Greenlight’s advanced development candidates is an excellent example of the benefit of the precision feature of this RNA-based technology. There is a parasite of honeybees called the Varroa mite.  Populations of these mites can infest beehives where the individuals then attach themselves to the body of a bee and sucks its bodily fluid. The mites also spread deadly viruses and this pest/virus complex is the biggest challenge facing commercial beekeepers. This RNA technology is expected to precisely target the mites without hurting the bees.

Credit: USDA-ARS/Steve Asmus

Greenlight has other insect control RNA products in the pipeline as well as controls for some fungal diseases including Powdery Mildew and Botrytis — both important diseases of grapes and other crops. 

Another company called RNAiSSANCE AG also has novel RNA-based insect and disease control products in development. In the not-too-distant future, this technology could help with the control of the Diamond Back Moth, Fall Army Worm, Two Spotted Spider Mites, Rice Blast and Banana Sigatoka.

What it took to get to this point: There are some unique challenges for the technology that had to be overcome before it could move on to commercialization. The first was developing cost-effective manufacturing methods; that issue took some time to solve. After years of research both Greenlight and RNAiSSANCE now report that their costs are under $1/kg which puts them in an affordable range for developers and, ultimately, farmers. That could mean many more new candidates could enter the field-testing stage. 

The other issue is both an advantage and a challenge. RNA breaks down very quickly in the environment, which means that there are no residue issues from a safety and environmental point of view. But it can also be a problem in terms of having the agent active long enough to expose enough of the pest population to be effective. 

As with synthetic, natural product and biological pest management products, the solution is likely to be found with “formulation” technology. There are many well characterized “inert ingredients” that are used to enhance product performance and refining those will be a key part of the innovation process for RNA-based pesticides going forward.

If a given pesticide is used too frequently, it is likely to select for resistant forms of the pest in the same way that excess use of human antibiotics can select for resistant strains. In a good integrated pest management program, pesticides with different “modes of action” are either alternated or combined to reduce that selection pressure. It is difficult to discover new synthetic products that have novel modes of action, but with the RNA approach many new options are likely to emerge that wouldn’t otherwise be possible. When these products are commercialized, it will be important to integrate them with other tools to manage the risk of resistance development for both the traditional chemicals and the RNA products.

Lowering development hurdles

The other big potential plus for RNA products is that once the new regulatory track for these products has been successfully pioneered, the cost to develop new products likely will be far lower than for synthetic chemical options, and that the development time-line will be far shorter. One study from Purdue University estimated that the cost of discovering, developing, and registering a new pesticide active ingredient exceeds $180 million and the process takes around a decade. The current numbers may well be higher. There are only a handful of companies left in the world that could keep making that scale of investment, so a faster track would be very helpful.

These earth-friendly developments have sparked a great deal of interest in seeing how these new products will perform. They will not displace the need for the other chemical, biological and genetic solutions, but they are likely to make IPM programs more robust going forward. As with any new pest management option the true test will play out on the farm. Hopefully that process will begin in the US in 2023. 

Steve Savage is a plant pathologist and senior contributor to the GLP. Follow Steve on Twitter @grapedoc

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