What can we expect from new herbicide modes of action or other technologies?

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Discovering a new herbicide mode of action is a priority in both the private and public sectors. Some of the major herbicide manufacturers have increased efforts to discover new herbicide molecules. Both private and public institutions are looking for naturally occurring or novel compounds that could be developed into effective commercial herbicides (Figure 25). Several startup companies are also investing in the search. Newer herbicide discovery technologies should help with these efforts, including artificial intelligence, X-ray crystallography, and the use of DNA-encoded libraries.

One of the biggest differences in today’s search compared to past efforts is that companies now investigate the mode of action early in the discovery process. Companies identify critical new enzymes and search for molecules that inhibit them, thus targeting enzymes that have not been targeted previously.

If a new effective herbicide mode of action comes to the marketplace, what’s the chance for resistance evolution? Assuming the new mode of action targets a protein/enzyme that is an essential critical pathway for plant growth and development, the potential for resistance evolution remains high, if – as in the past – the new product is widely adopted and frequently used. More novel chemical solutions that do not rely on targeting single pathways in plants may have greater longevity, but they are much more difficult to discover and develop. The bottom line is that farmers will need to use a wider variety of weed management techniques now and into the future to prevent and manage herbicide-resistant weeds.

Figure 25. Herbicide discovery efforts seeking out new modes of action, such as in vitro assays to screen herbicide modes of action (middle), are on the rise from both major herbicide manufacturers and some newer startups, as well as the public sector. Private sector research and development teams include scientists and associates guiding robust discovery and development pipelines. (Photo credits: Top: Csail.mit.edu News, Feb. 20, 2020; Middle: Plant and Soil Sciences eLibrary, University of Nebraska, Lincoln; Bottom: https://www.fmc.com/en/innovation/research-development).

The future of discovering new and novel herbicides and other chemical solutions has many challenges, but also holds promise. Natural products are the byproducts of microorganisms or plant extracts. Very few of the world’s potential natural products have been screened for herbicidal activity, and several plant extracts show promise as cost-effective commercial herbicides. Unfortunately, very few bioherbicides have been commercialized as production and formulation challenges continued to complicate their success. However, in the effort to develop these compounds, scientists can sometimes discover new herbicide target sites. For example, glufosinate, a Group 10 herbicide discovered back in the 1970s, was developed based on phosphinothricin, a byproduct produced by Streptomyces bacteria.

RNA interference (RNAi) technology is under investigation as a tool to silence key plant genes leading to either enhanced susceptibility to herbicides or outright control of resistant weeds (Westwood et al. 2018). Most of this research has studied RNAi herbicides applied as a spray to target a specific weed species or groups of related species. In addition to weed management, researchers are developing and studying RNAi technology to manage insect pests and plant pathogens, as well as treat human disease. Challenges include survival in the environment, formulation, large-scale production, and product registration.

Synergists, chemical additives that enhance the effectiveness of a chemical, are also an area of interest for researchers looking to combat metabolic resistance. The presence of metabolic resistance eliminates the effectiveness of several current herbicide groups and could render a new mode of action ineffective before it even reaches the marketplace. The idea of adding a synergist to the herbicide spray to counteract the herbicide-degrading enzymes (such as cytochrome P450s or glutathione-S-transferases) is appealing. However, as Shaner and Beckie point out in a 2014 paper, one of the biggest challenges in using this approach is avoiding harming the crop, in addition to the weeds.

Finally, the development of new herbicide-resistant crop technologies could also provide some relief. Some of this discussion centers on developing new, nonselective or broad-spectrum herbicides with novel modes of action not prone to resistance in conjunction with crops that have been engineered to resist the herbicides.