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The future of weed management may be seed prevention technologies

Eons before chemists invented herbicides, waterhemp and Palmer amaranth slugged it out with stressors for survival.

“Some microorganisms produced compounds toxic to these plants,” says Pat Tranel, a University of Illinois (U of I) weed scientist. To survive, these pigweed family members formed enzymes to detoxify the substances. Unfortunately, the enzymes have a modern metabolic use.

“Some of these enzymes just so happen to also detoxify herbicide molecules,” says Tranel. This enables these pigweeds to render herbicides useless, akin to the way corn metabolizes atrazine as it simultaneously slays broadleaf weeds. Hello, metabolic resistance.

“It’s scary,” says Bill Johnson, Purdue University Extension weed specialist. “It can quickly render multiple herbicides ineffective across a large number of fields.”

It’s a reason why waterhemp and Palmer amaranth now resist seven and nine herbicide sites of action, respectively. So far, metabolic resistance impacts mostly grasses and outcrossed weeds, such as waterhemp and Palmer amaranth. (Outcrossed weeds are those that pollinate different plants of the same species.)

Metabolic resistance development is likely slower in self-pollinated broadleaf weeds such as marestail, says Tranel.

“As we go along, though, all weeds have the potential to develop metabolic resistance,” says Tranel.

This may spur weed management away from a herbicide focus and toward technologies that focus on nixing seed development, such as irradiated pollen and genetic weed seed modification.

“A decade from now, we may look back at this time as the beginning of the end of the chemical era of weed control,” adds Tranel.


Pat Tranel

Target-site resistance

Herbicides kill weeds by binding to an enzyme in an essential biochemical pathway, says Tranel. Target-site resistance disrupts this process. It occurs when the gene that encodes a particular enzyme changes its structure so the herbicide no longer binds to it. This ensures survival of a weed that through its seed spawns more herbicide-resistant weeds.

“When you have targetsite resistance to one herbicide, that weed is typically going to resist other herbicides that share the same target site,” says Tranel.

For example, waterhemp that resists Cobra (Group 14) will also resist Flexstar, another Group 14 herbicide.

The good news? Targetsite resistance does not confer resistance outside a herbicide group.

For example, Group 14 resistance doesn’t jump to Group 10 herbicides such as glufosinate. Thus, it's manageable.

“Applying effective herbicides in mixtures and annual rotations that have different target sites effectively delay the evolution of target-site resistance,” says Tranel.


Meet metabolic resistance

Metabolic resistance works differently in unpredictable patterns. Weeds use a multistep process that may involve many different enzymes — including glutathione S-transferases (GST) and P450 — to detoxify a herbicide.

“Plants [weeds included] have dozens, if not hundreds of different types of enzymes, any of which could potentially metabolize a herbicide,” says Tranel. “It’s not just a P450 causing the metabolic resistance, but perhaps the P450 plus a GST plus an ABC transporter, all of which work together to get rid of a herbicide faster.”

This creates enzyme stacking, akin to seed stacks that feature herbicide-tolerant and insect-resistant traits. 

“Once these enzymes accumulate in a [weed] population, they typically don’t go away,” says Tranel. “They just keep stacking on each other, and that causes the loss of effectiveness of a broad range of herbicides.”

Unpredictability reigns, because resistance can wildly jump to other herbicide sites of action, he adds.

In one case, watergrass in a California rice field metabolically resisted 16 herbicides spanning six herbicide sites of action.

“It [metabolic resistance] can even encompass herbicides that have not even been identified,” says Tranel. “There have been at least two instances from two different companies that had a new active ingredient. They looked promising, but when the companies tested them on pigweed populations, they discovered the weeds already had metabolic resistance to them.”

Metabolic resistance and its ability to form cross-resistance to multiple herbicide sites of action complicates herbicide discovery, says Dane Bowers, Syngenta technical product lead.

To combat the issue, Syngenta is using intelligent design, a scientific process that addresses undirected randomness that occurs through phenomena such as metabolic resistance.

“We have the ability to screen new herbicides in our development pipeline against the different resistance mechanisms,” says Bowers. “This provides us with the knowledge early on in the development process to assess the viability of a new active ingredient.”



Molecular handles

Weed scientists also are aiming to identify molecular handles to defuse metabolic resistance’s unpredictability. A molecular handle identifies a common enzyme that detoxifies different herbicide sites of action, says Tranel. Seed companies use them in developing trait technology, such as the Enlist Weed Control System that confers tolerance to multiple herbicides that include 2,4- D choline (Group 10) and quizalofop (Group 1), he says.

Successfully identifying molecular handles could spur creation of a color-coded chart linking enzymes with the herbicides they metabolize. “We could then rotate herbicides based on their metabolic potential,” says Tranel. Genomics and RNAi technology also hold potential ways to decipher metabolic resistance, he adds.

What to do now

“To think that weeds could be resistant to chemicals not even invented yet is troubling,” says Marc Kaiser, who farms near Carrollton, Missouri. He’s rotated herbicide-tolerant trait packages and different herbicide sites of action, which is a time-tested way to forestall target-site resistance.

Unfortunately, this strategy may not work with metabolic resistance.

“A study in the United Kingdom with blackgrass showed that if farmers use mixtures of herbicides, they’re likely to end up with more metabolic resistance,” says Todd Gaines, a Colorado State University weed scientist. It’s unknown if this extends to all weeds, he adds.

Still, keep rotating.

“We still encourage farmers to mix and rotate herbicides,” adds Tranel. “Even though metabolic resistance is becoming more common, target-site resistance is not going away.”

To forestall metabolic resistance, weed scientists advise farmers to:

  • Control weeds early. “Oftentimes as weeds get older, they express more enzymes and have more metabolic herbicide detoxification potential,” says Tranel. It’s not foolproof, though, as U of I weed scientists confirmed young waterhemp populations metabolically resistant to preemergence Group 15 herbicides in 2019.
  • Judiciously apply herbicides. “Preventing metabolic resistance comes down to exposing less weeds to herbicides,” says Tranel. Each time farmers apply herbicides to weeds, resistant weeds survive and eventually multiply, he adds. It’s a tough sell. “Economics in the Midwest makes corn-soybeans the optimal rotation, but it’s not the optimal rotation for weed control and weed management,” says Tranel. “I’m not saying we will stop using herbicides, but we need to expose fewer weeds to herbicides.”
  • Diversify crop rotations. Waterhemp and Palmer amaranth thrive in crops such as corn and soybeans, because all are summer annual plants, says Tranel. Planting a winter annual crop such as winter wheat or a perennial such as alfalfa clips pigweed growth potential. “If you plant alfalfa in a field for two to four years, it won’t get rid of the waterhemp [or Palmer amaranth], but it will dramatically reduce populations,” he says.
  • Plant cover crops in narrow soybean rows and use harvest weed seed control. Besides enhancing efficacy of postemergence herbicides, these steps can reduce the weed seed bank over time, says Prashant Jha, Iowa State University Extension weed specialist. “This can reduce selection pressure for development of resistant weeds,” he adds.

Decade look back and look ahead

“This is similar to glyphosate about a decade ago, when we recognized it was the beginning of the end for its use as a stand-alone herbicide,” says Tranel. “It didn’t mean we stopped using glyphosate, but we could no longer solely rely on it. Maybe a decade from now, this also will apply broadly to use of herbicides due to metabolic resistance."

Irradiated Pollen

Palmer amaranth is a formidable foe, as one plant may shower up to 250,000 seeds into the soil from a 10-foot height on a stalk as thick as a baseball bat. Still, scientists for the Israeli firm WeedOUT are hitting it where it hurts — its pollen and, subsequently, its seed.

WeedOUT has developed a process that uses irradiated male Palmer amaranth pollen to successfully compete with natural pollen. The irradiated pollen forms a nonviable seed when it fertilizes a female Palmer amaranth plant’s ovule.

The technology is designed for weeds that cross-pollinate, including dioecious weeds (containing both male and females) such as Palmer amaranth. This technology will be part of an integrated weed management approach, say WeedOUT officials.


At season’s start, farmers will spray preemergence and postemergence herbicides as needed, followed by the three applications of pollen during Palmer amaranth’s flowering season.

In 2021, Stanley Culpepper, a University of Georgia weed scientist, first applied dicamba to control Palmer amaranth in cotton plots followed by three applications of irradiated pollen. The irradiated pollen reduced normal weed seed formation by 79% compared to plots without pollen applications. This reduction will crimp future weed seed germination, say WeedOUT scientists.

“Farmers will be able to start the next year with much cleaner fields with far less [herbicide] resistant weeds,” says Orly Noivirt-Brik, co-CEO of WeedOUT.

The company is currently developing a liquid formulation for applying the irradiated pollen.

“Developing the wet formulation was challenging for biological and physical reasons,” says Zeev Weiss, WeedOUT president. “The natural environment of pollen is not a wet formulation, because pollen moves by the wind.”

Applicators will be able to apply the liquid formulation through conventional sprayers or unmanned aerial vehicles, he says. Company scientists are planning to further test the technology in more U.S. locations in anticipation of a 2025 U.S. commercial launch.

Odds of weeds resisting the technology are low, as weed enzymes are not involved as they are with herbicide resistance, says Weiss. “Because we’re addressing the reproductive system of the plant, it is much less vulnerable to development of resistance,” he adds.

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