During the past 30 yr an impasse has developed in the discovery and commercialization of synthetic herbicides with new molecular targets and novel chemistries. Similarly, there has been little success with bioherbicides, both microbial and chemical. These bioherbicides are needed to combat fast-growing herbicide resistance and to fulfill the need for more environmentally and toxicologically safe herbicides. In response to this substantial and growing opportunity, numerous start-up companies are utilizing novel approaches to provide new tools for weed management. These diverse new tools broaden the scope of discovery, encompassing advanced computational, bioinformatic, and imaging platforms; plant genome–editing and targeted protein degradation technologies; and machine learning and artificial intelligence (AI)-based strategies. This review contains summaries of the presentations of 10 such companies that took part in a symposium held at the WSSA annual meeting in 2024. Four of the companies are developing microbial bioherbicides or natural product–based herbicides, and the other six are using advanced technologies, such as AI, to accelerate the discovery of herbicides with novel molecular target sites or to develop non-GMO, herbicide-resistant crops.

Parasitic witchweeds inflict most of their damage while still underground and attached to crop roots. Most selective translocated herbicides are detoxified by crops such as corn and thus cannot reach the attached parasites. Corn with target site resistance to acetolactate synthase (ALS)-inhibiting herbicides was tested to ascertain whether these herbicides could control witchweeds, assuming that witchweeds do not obtain amino acids from the crop. Postemergence directed sprays of 27 g ae ha−1 imazapyr 54 d after planting (DAP) delayed Striga asiatica emergence on corn in South Carolina from 3 wk (control) to 7 wk and to 11 wk when mixed with 45 g ae ha−1 AC 263 222. Treatments with up to 71 g ae ha−1 imazamox, and up to 71 g ae ha−1 AC 263 222 only delayed Striga emergence by 1 wk, and 71 g ae ha−1 imazethapyr was ineffective. ALS-inhibiting herbicides were far more effective when applied in 1-ml drenches above the seed at planting. Chlorsulfuron (10 g ai ha−1) and sulfometuron (50 g ai ha−1) were somewhat phytotoxic to Pioneer 3245IR. Rimsulfuron (30 g ai ha−1), metsulfuron (10 g ai ha−1), halosulfuron (120 g ai ha−1), and imazethapyr (140 g ae ha−1) were marginally active in Kenya, with some mature Striga hermonthica seed-bearing capsules appearing at harvest (12 wk). Imazapyr at 15 g ae ha−1 gave 70 to 95% suppression of capsule formation, whereas no capsules appeared at 30 g ae ha−1. The use of imazapyr in Kenya increased the harvest index by 17% when corn plants in Striga-infested soils were kept insect and disease free by using insecticides and fungicides. Thus, complete control can be achieved at affordable cost by farmers in subsistence conditions.

Weed science is responsible for reducing weed competition with crops, within constraints, allowing food production for a growing world population. We have been successful, but with an increasing reliance on the fantastic arsenal of herbicides. Heavy herbicide usage and the concomitant loss of control due to changing weed species spectra, as well as evolved herbicide resistance, along with cancellations of registrations, limit chemical options. Old “innovations” such as well-conceived rotations and various mechanical procedures partly alleviate chemical dependency. We must try innovative, meaningful herbicide mixtures, whether synergistic or additive, mixtures of crop varieties, more competitive varieties, including allelopathic varieties, which could all help to lower chemical dependency. Three cases where innovative genetic-engineering coupled with chemistry seem to be needed are: (a) for the control of parasitic higher plant weeds such as broomrapes (Orobanche spp.), dodders (Cuscuta spp.), witchweeds (Striga spp.) that cannot be controlled by mechanical or selective chemical means with a sufficient margin of user error; (b) for the control of weeds in wheat (Triticum spp.) that are evolving multiple and cross resistances to all wheat-selective herbicides; and (c) to replace the major s-triazine and chloroacetamide herbicides in corn (Zea mays L.) that are under attack and where many local restrictions and cancellations have been imposed. We need better replacements than the resistance-prone inhibitors of acetolactate-synthase and acetyl-CoA-carboxylase. Much of the long-term innovative planning and research must come from the public sector as no one else seems willing to fill the needs.

A triazine-resistant (R) biotype of a Graminaceous weed, Brachypodium distachyon (= Trachynia distachya), was found in the lower Galilee area of Israel after repeated treatments of roadsides with simazine [2-chloro-4,6-bis (ethylamino)-s-triazine] and atrazine [2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine]. It was not affected at levels up to 3.0 kg/ha of soil-incorporated atrazine or simazine. The (R) biotype was unaffected by atrazine, as ascertained by measuring whole-leaf and plastid fluorescences and the Hill reaction. The triazine-sensitive (S) biotype was inhibited in all these reactions. The data suggest that the (R) biotype has a plastid mode of resistance common to many weed species. The (R) biotype metabolized 14C-(ring)-atrazine more rapidly to both water-soluble and to chloroform-soluble compounds than the (S) biotype did, but that could not explain the immediate resistance at the plastid level. Probably there was evolution towards increased tolerance by detoxification as well as plastid level resistance.

A group of scientists from academia, government, and industry, along with ecologists, regulators, conservationists, and grower representatives have formed an International Organization for Resistant Pest Management (IOPRM) to review and delineate proactive and retroactive management strategies for specific cases of pesticide resistance. Within IOPRM, technical working groups were appointed to deal with each pest group. The Weed Resistance Management Working Group (WRMWG) is chaired by Drs. Jonathan Gressel and Leonard Saari, and will deal with the analysis and promoting of alternative control strategies for case studies where a high risk of herbicide resistant weeds exists. Based on our experience to date, crops such as wheat, corn, and soybeans and weeds such as kochia, annual ryegrass and blackgrass, will be used as models to develop optimum weed resistance management programs. The group is especially looking for herbicide and weed control data on negative-cross resistance, econometric models, novel management procedures, and quantitative data from weed scientists and other research and extension communities that could facilitate reaching optimal management decisions. All recommendations and experiences will be communicated through a worldwide network.

Herbicide-resistant populations have evolved only in monoculture and/or monoherbicide conditions at predictable rates for each compound and weed. No populations of triazine-resistant weeds have appeared in corn where rotations of crops and herbicides or herbicide mixtures were used. This is due to the greatly reduced competitive fitness of the resistant individuals, which could be expressed only during rotational cycles, and also to the greater sensitivity of resistant individuals to other herbicides, pests, and control practices (“negative cross-resistance”). The model presented here describes how an understanding of all of these factors can provide strategies to decrease the frequency of the resistant individuals during rotation. Rotations or mixtures may not delay the rate of appearance of resistance to inhibitors of acetolactate synthase (ALS), where the fitness of resistant biotypes is claimed to be near normal. The best way to delay resistance to ALS inhibitors is to use those compounds with less persistence so that the selection pressure will be lowered. Too little is known about the frequency of resistance to other herbicides with target-site resistance–to dinitroanilines, to acetyl CoA carboxylase inhibitors, or to those situations where a single enzyme system confers resistance to a broad spectrum of seemingly unrelated herbicides.

Mixtures of herbicides have been proposed as strategies to prevent or delay the evolution of resistance to the resistance-prone sulfonylurea and imidazolinone herbicides that inhibit acetolactate synthase. These herbicides have become or are becoming widely used in soybean, wheat, rice, and other major crops. For a mixture to be efficacious in preventing resistance, the less resistance-prone component(s) should have the following traits compared to the vulnerable herbicide: a) control the same spectra of weeds; b) have the same persistence; c) have a different target site; d) be degraded in a different manner; and e) preferably exert negative cross-resistance. We compared the proposed mixing partners for use with several widely used acetolactate synthase inhibiting herbicides to these criteria and found that: a) all have somewhat different weed spectra; e.g. none control common cocklebur as well as imazaquin or imazethapyr in soybean, or kochia as well as chlorsulfuron in winter wheat; b) all are far less persistent than these vulnerable herbicides. Less persistent sulfonylureas are now on the market but are in limited use. Late in the season, the mixing partner is not present while the vulnerable herbicide remains active; c) most have different target sites; d) in soybean most mixing partners are degraded differently than vulnerable herbicides. In wheat virtually all herbicides used without safeners are degraded by monooxygenases, thus it is impossible to meet this criterion in this crop; e) none of the mixing partners exert negative cross-resistance. The present mixtures may have superior or more cost-effective weed control properties than the acetolactate synthase inhibitors used alone, but they do not meet all the criteria for resistance management. Not meeting the key criteria of identical control spectra and equal persistence aggravates future resistance problems, as has happened with insecticides.

Except for a small number of cases in which biocontrol agents were introduced from the site of origin of a weed (classical biocontrol), there have been few cases where a pathogen was virulent enough to perform cost effectively in the field as a mycoherbicide. Mycoherbicides are typically weed species specific, so compatibility with herbicides used to control other weeds is often studied. There can be a synergy between mycoherbicides and herbicides at the field level due to overlapping weed spectra (such synergies are not discussed in depth herein). Two approaches have been used to ascertain whether there is synergy in controlling the target weed: (1) random screening with herbicides; (2) using herbicides as antimetabolites to inhibit specific pathways, enhancing virulence. Glyphosate is the most common herbicide to synergize mycoherbicides, possibly due to its dual function as an inhibitor of biosynthesis of phenylpropanoid phytoalexins by suppressing enolphosphate-shikimate phosphate synthase, or by suppressing callose production (by inhibiting callose synthase) as well as inhibiting other calcium-dependent pathways due to the calcium-chelating properties of glyphosate.

Whole-plant, negative cross-resistance was studied in Conyza canadensis and Echinochloa crus-galli, important global weeds. Negative cross-resistance can be a most useful preemptive, cost-effective tool for delaying the evolution of resistance, as well as for resistance management, after resistant populations evolve. Seeds of triazine-resistant and -susceptible biotypes were collected in or near orchards that had been continuously treated with atrazine for more than 10 yr. Plants grown from the seeds were treated, in a greenhouse, with herbicides from the following chemical families: triazine, benzothiadiazole, phenyl-pyridazine, arylophenoxy-propionate, cyclohexanedione, phenoxycarboxylic acid, pyridine carboxylic acid, phosphinic acid, glycine phosphate, chloroacetamide, sulfonylurea, and bipyridylium. Eleven of the 18 herbicides tested exerted significant negative cross-resistance against atrazine-resistant weeds, ranging from 0.03 to 0.67 of the concentration required to affect the triazine-sensitive type. No synergism was found between bentazon and fluroxypyr in mixture on Conyza, even though both separately exerted negative cross-resistance. Using a mixture with half the amount of each component lowers the environmental effect of each component while controlling a broader spectrum of other weeds.

Striga is a major constraint to food production in Africa. Most technologies developed for the eradication of Striga asiatica from the United States are not adaptable to Africa. Imazapyr and pyrithiobac coated imidazolinone-resistant (IR)-resistant maize seed prior to planting at rates of 30 to 45 g ha−1 provide near season long control of Striga and can increase maize yields three- to fourfold if supplied with fertilizer. Slow release seed coatings reduce maize injury when post-planting rains are sparse and improve Striga control when there is excessive rainfall early in the season. Models suggest that herbicide resistance may not be a significant threat in short season maize, but vigilance in removing flowering Striga plants that are not controlled is recommended due to the known risk of evolution of resistance to these herbicides. Stacking the IR gene with glyphosate resistance and using imazapyr treated seed and applying glyphosate mid-season would provide season long Striga control and delay the evolution of resistance to both herbicides. To date, adoption of this technology has been limited by a number of factors. However, it should be included as one component of a multi-factor approach to increasing maize productivity in areas of Africa where Striga is problematic.