Regulating Herbicide Resistance

2,4-dichlorophenoxyacetic acid (3D model)

A few months ago, I wrote about 2,4-D resistant corn and soybean. At that time, the USDA had just completed it’s draft environmental impact statement for the two crops. While the USDA regulates crops developed through biotechnology, it is the EPA that regulates pesticide use. So before the new formulation of 2,4-D can be applied to the new corn and soybean varieties, it will need to be approved for use by the EPA. The comment period for the 2,4-D draft label is currently open until June 30, 2014.

I was a little surprised to see a recent Nature editorial about the EPA’s review process, (even though Nature has discussed “superweeds” before). It seems the Nature editorial staff thinks that although the draft assessment “offers sensible precautions,” the EPA “could do much more” to reduce herbicide resistance:

“When an insect-resistant variety of genetically engineered crop was released, US regulators required farmers to plant nearby refuges of non-resistant plants to ease the selection pressure on insects to develop resistance to the crops. Similar measures for herbicide-tolerant crops might require farmers to rotate crops or herbicides every few years — a familiar restriction, because many herbicides have limits on how often they can be used for environmental reasons. Such measures would be a sign that regulators and farmers alike have realized the consequences of underestimating the ability of weeds to develop resistance.” –Nature Editorial Staff

They seem to suggest that EPA should include regulations that reduce the potential for herbicide resistance development. In principle, I agree that some sane regulations that encourage more sustainable herbicide use could be a good thing. Herbicide resistance, though, is a very complex problem. Regulations aimed at solving complex problems are always difficult to implement, may have some unintended consequences, and will certainly be contentious among interested parties (think health care or energy policy). This doesn’t mean they should be discarded without consideration, though, and I would support regulations if convinced they would be effective with minimal negative impact. Nathanael Johnson has just written a very nice piece summarizing how difficult it would be to implement regulations that reduce herbicide resistant weed development. Any restrictions imposed by the EPA would need to be considered very carefully, with lots of input from scientists working in weed management to try and avoid inadvertently exacerbating weed problems. I’ve spent some time thinking about this recently (mostly in the backseat of a car, in airports and on planes while travelling the last 2 weeks). Although I’m quoted in Johnson’s piece, I wanted to provide some details here.

Regulating the herbicide resistance trait/crop

One way to manage herbicide resistant weed development would be to try and regulate use of the trait directly. For herbicide resistance, this would fall under USDA’s authority rather than EPA’s. As far as I know, there is no current precedent for the government to require farmers to rotate from one crop to another. Doing so could limit the ability of a grower to respond to market changes, and would probably bring up many legal issues on the role of the federal government. Although I think we should encourage diverse crop rotations, it would be an extremely difficult practice to regulate. There are examples of crop rotation requirements, though, outside of Federal regulations. Many sugarbeet cooperatives require a 2 to 4 year crop rotation to reduce plant disease pressure. Certified seed producers are often prohibited from growing the same crop in the same field in consecutive years for similar reasons. But both of these restrictions are imposed by industry market forces, not by government regulations.

Regulations that limit planting of the herbicide resistant (HR) crop itself are, in theory, similar to the Bt refuge practice. The Nature editorial mentions the refuge for Bt crpps as an example where this has already been done, and at first glance, this seems a reasonable comparison. Growers could be restricted to planting HR varieties on a set percentage of total crop land (say 50% of acres). Regulating the amount of the HR crop planted could reduce selection for resistant weeds by limiting acreage of the trait, thereby limiting use of the herbicide it was designed to withstand. Perhaps this could be effective, but I’m not aware of any good science that would give a clear picture of how to best implement a restriction like this. Any percentage chosen would be pretty arbitrary. Is 50% enough? How should it be spatially arranged? Would 50% be more effective than 70%? Should the restrictions be the same for corn and soybean, or would the competitive differences between crops warrant different percentages? And should it be different depending on which weeds are in the field? There are really no good answers to these questions.

Biological and ecological differences between weeds and insects further confound the comparison between insecticide and herbicide resistance management. The Bt traits target specific insect pests, whereas herbicide resistance traits are used to control a wide variety of weeds. What may work for one weed species may not work for others. The insects targeted by Bt are also pretty mobile during their reproductive stage. Corn rootworm beetles and European corn borer moths can move easily between the treated areas and refuge areas, which allows mating between the resistant and susceptible individuals. This is the whole idea behind refuge areas. When susceptible and resistant biotypes interbreed, the resistance trait is diluted within the population reducing the chances resistance becomes an economic problem. (Yes, my entomologist friends, it is indeed a little more complex than that, but I’m simply drawing the distinction between weeds and bugs. Cut me a little slack…)

Weeds, on the other hand, don’t move very much during their reproductive stage. In fact, weeds don’t move at all in corn and soybean fields during flowering and pollination, so the inter-mating between a susceptible plant and a resistant plant would be limited by pollen movement. The distance viable pollen can travel varies quite a lot for different weed species. The one consistent rule is that as distance between two plants increases, the amount of cross-pollination between them decreases. If susceptible and resistant weeds are separated by more than just a few meters, it is doubtful there would be enough inter-breeding between them to have much impact on resistance evolution in the field. So a refuge area for weeds is unlikely to be helpful as it is for insects.

Finally, unlike Bt crops, planting the HR variety doesn’t require the use of the associated pesticide. When you plant Bt crops, the Bt is always there; the HR trait allows use of a herbicide, but does not require it. This is an important difference that makes regulating Bt and HR crops inherently different. A farmer could plant 100% of her acreage to a particular HR trait without applying the herbicide at all. This is unlikely, but it is certainly plausible that not all of the HR crop acres will receive the herbicide. Since it is the herbicide that selects for resistant weeds, restricting use of the crop is probably far more complex and less effective compared to regulating herbicide use directly. Therefore, if the goal is limiting herbicide resistant weed evolution, perhaps it is more reasonable to regulate herbicide use, rather than the HR trait.

Regulating herbicide use for resistance management

The EPA is no stranger to regulating pesticide use, so limiting the amount of herbicide applied to a given area would be well within their area of expertise. All herbicides already have a maximum annual application rate, and applying more than this amount is prohibited by law. It is possible that these restrictions could be leveraged to reduce selection for herbicide resistant weeds. Frequency of herbicide use is generally agreed to be the primary driver of resistance evolution, so EPA could simply limit the amount of each herbicide that could be applied in a given time period. This could certainly be implemented if we were only worried about reducing resistance to a single herbicide (in this case, probably 2,4-D or glyphosate). However, herbicide resistance is a problem for all herbicides, not just those we’ve engineered crops to resist. If we want to tackle herbicide resistant weeds, we shouldn’t be focused on only one or two herbicides. Only regulating glyphosate or 2,4-D use, or any other particular herbicide, seems an arbitrary and non-scientific way to regulate herbicide resistance. And, in fact, it could make the resistance problem worse.

Let’s say, for example, the EPA chose to limit the amount of 2,4-D and glyphosate that could be applied in an effort to reduce the selection pressure for resistant weeds. Under these theoretical EPA restrictions, growers might only be allowed to apply glyphosate and 2,4-D once every 2 years. In the year when the grower is not using 2,4-D or glyphosate, the grower could potentially choose to spray an ALS-inhibiting herbicide and atrazine. Resistance to these herbicides is already widespread, and, therefore, it is likely that resistance to these herbicides could become worse if glyphosate and 2,4-D are not allowed to be used.  Which brings us to:

The resistance management paradox

Complete removal of herbicides from agriculture would have a dramatic negative impact on crop production. At least in the short term, complete conversion to non-herbicide methods is simply not realistic. The following discussion, then, is based on the premise that herbicides are a necessary part of crop production, at least for the foreseeable future. (If you disagree with this premise, that is fine, but it will be difficult to engage in a fruitful discussion of reasonable herbicide regulations without first acknowledging that herbicides are an important production tool.) The only way to assuredly prevent herbicide resistance from evolving is never to apply the herbicide; but if we are going to use a herbicide, the best way to minimize herbicide resistant weed evolution may be to increase herbicide use.

Research from Hugh Beckie and Xavier Reboud has shown that mixtures of two herbicides are far more effective at slowing the evolution of herbicide resistant weeds compared to an annual rotation of herbicides. In this research Beckie & Reboud seeded a field with an experimental population of field pennycress. The seeded population had a known proportion of herbicide-resistant and -susceptible plants (5% resistant, 95% susceptible to ALS-inhibitor herbicides). They then applied an ALS herbicide in different use patterns to see how quickly the resistant plants increased within the population. Their results were pretty definitive; If they used the ALS-inhibiting herbicide by itself just one time over a 4 year period, they observed nearly a 6-fold increase in prevalence of resistant weeds. However, if they applied the ALS-inhibiting herbicide every year, but mixed it with another effective herbicide, the resistant weeds remained the same as if they had never used an ALS-inhibitor at all. The lesson here is that using a herbicide by itself, even one time, will select for resistant weeds. But because it is much more unlikely that any given weed will have multiple resistance traits, the best way to use a herbicide is to combine it with a second herbicide that is equally effective on the target weed. If we consider herbicide-resistant weeds to be an environmental problem that must be addressed, one strategy we must seriously contemplate is increasing herbicide use. Requiring an increase in herbicide use through government regulations, however, is something that I’m sure all sides can agree is a bad idea.

The tank-mix strategy is particularly relevant for the herbicide-resistance traits under consideration, though. Enlist corn and soybean have both glyphosate and 2,4-D resistance. This will allow spraying a mixture of glyphosate and 2,4-D and will almost certainly slow the development of herbicide resistance in most weeds. But there are exceptions. In order for herbicide tank-mixtures to delay the evolution of resistance, both herbicides must be effective on the target weed. If one of the herbicides is not effective, then there is still heavy selection pressure for weeds resistant to the other herbicide. For example, a grower might use the new Enlist herbicide (mixture of glyphosate and 2,4-D) to control Johnsongrass. Because 2,4-D doesn’t provide much control of Johnsongrass, the grower would continue to select for glyphosate resistant individuals. Another example would be using the Enlist herbicide to control glyphosate-resistant weeds. Since the glyphosate would not be providing any control of the resistant biotypes, there would be heavy selection for 2,4-D resistant individuals, eventually resulting in weeds resistant to multiple herbicides. The herbicide tank-mixture approach only works for resistance management when both herbicides are effective on the target weeds. This will require some education efforts so that growers are not lulled into a false sense of security. It will also be important that industry resists the urge to market herbicide products for “herbicide resistance management.” To be sure, herbicide resistance management does not come in a jug.

The tank-mixture strategy also only works with the most common resistance mechanisms. Other types of herbicide resistance (like metabolic resistance) are potentially more likely to occur when multiple herbicides are used. Although metabolic resistance mechanisms are currently the exception rather than the rule, there are more instances being confirmed each year, and it is likely that more will be documented in the future, especially as tank-mixtures become more widely used for resistance management.

As Nathanael Johnson states in his piece “It’s tricky for a bureaucracy in Washington, D.C., to make good decisions for a multitude of farmers in different areas.” Each region deals with different crop rotations, different herbicides, and different weed species. There are simply no silver bullets when it comes to managing weeds. I think we need to continue finding ways to manage weeds (with and without herbicides) that are practical and economical. These practices will vary greatly based on geography and other social factors. Unfortunately it just isn’t as simple as “doing much more.”

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