5   Herbicide-Resistant Transgenic Crops

Herbicides entered U.S. agriculture after World War II. The first commercially available herbicide was 2,4 dichlorophenoxy-acetic acid (2,4-D), introduced in 1946.1 It was developed during the war by independent research groups in the United States and the United Kingdom under conditions of wartime secrecy. Scientists were looking for chemical warfare agents (biocides) that could be used to destroy agricultural fields of Germany and Japan and create famine as an ancillary military strategy to conventional ground warfare and aerial bombing.

In August 1944, the journal Science published one of the earliest nonclassified studies of 2,4-D and its use on bindweed: “By the fifth day following application of the spray, the basal leaves were yellow, and at ten days the above ground parts were dry and dead.”2

In her widely acclaimed 1962 book Silent Spring, Rachel Carson devoted several pages to 2,4-D, hinting at its toxicity and alerting readers to its unanticipated environmental effects: “With the widespread use of 2,4-D to control broad leaved weeds, grass weeds in particular have increasingly become a threat to corn and soybean yields.”3 Carson referred to 2,4-D as one of the most widely used herbicides of her day. The herbicide 2,4-D selectively controls broadleaf weeds but allows grasses to remain relatively unaffected.

From the farmer’s perspective, “herbicide treatments are an integral part of modern agriculture because they provide cost-effective increases in agricultural productivity.”4 Food crops fare better without competition from weeds for water, light, nutrients, and space and without contaminating weed seeds. Weeds often play a role as a host or shelter for plant pathogens that affect food crops in quality and quantity. Herbicides also help protect soil conservation by supporting no-till agriculture. Tillage (the turning over of soil) contributes to erosion, the reduction of soil fertility, and the loss of top soil. At first glance, herbicide-resistant (HR) plants can be seen as contributing to no-till agriculture, which helps to sustain the soil. But as Martin Paul Krayer von Krauss, Elizabeth A. Casman, and Mitchell J. Small note, after you take into consideration “volunteer plants” (plants found growing without having been planted), tillage creeps back in: “To counter the [herbicide]-tolerant volunteer problem, farmers will have two options: use additional herbicides or revert to tilling. Experts fear that the cost of the first option will exceed the cost of the second … a large-scale reversion to tilling would be expected, and the soil conservation and agronomic benefits of no-till agriculture would be lost.”5 Tillage also creeps back in when weeds become herbicide-resistant.

The use of herbicides in the United States increased dramatically in the last quarter of the twentieth century. In 1974, 800,000 pounds of glyphosate was used in U.S. agriculture, and by 1995, its use had tripled. Nearly twenty years later in 2014, its applications grew to 250 million pounds.6 Between 1974 and 2014, about 3.5 billion pounds of glyphosate was applied in the United States. According to the U.S. Department of Agriculture, “an overreliance on glyphosate and a reduction in the diversity of weed management practices adopted by crop producers have contributed to the evolution of glyphosate resistance in 14 weed species and biotypes in the United States.”7

The chemical glyphosate was first synthesized by a Swiss chemist in 1950 but not developed as an herbicide. It was rediscovered in 1970 by a Monsanto chemist who recognized its herbicidal properties.8 Glyphosate was patented and marketed in 1974 under the trade name Roundup. The herbicide won awards for the Monsanto chemist for its broad-spectrum effects that controlled both broadleaf and grass weeds and for what was then understood to be its low toxicity to animals compared to other herbicides. Prior to the development of recombinant DNA, herbicide resistance in plants was discovered by trial and error without an understanding of the mechanism that made crops tolerant to a specific herbicide. Some efforts were made to breed certain cultivars with herbicide resistance. Several canola varieties that were resistant to triazine (a family of herbicides) were released in the 1980s, but lower yields limited their commercial value. There were also some natural strains of rice that were resistant to imidazolinone. In the 1960s and 1970s, seed and herbicide manufacturers were different companies. There was no incentive for seed producers to breed herbicide-resistant crops or varieties to benefit chemical companies. That changed in the 1980s, when large chemical companies bought up seed producers.

Monsanto scientists discovered a gene for a glyphosate-insensitve form of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), an enzyme that is critical to plant growth and that was found in some microorganisms. After the EPSPS variant is incorporated into the plant genome, the gene product confers crop resistance to glyphosate. In 1996, Monsanto introduced transgenic glyphosate-resistant soybeans into U.S. agriculture and followed it with other crops (table 5.1). The seeds soon became commercially successful, and with that success, the company’s glyphosate formulation called Roundup became the leading herbicide applied in the United States.

Table 5.1

Herbicide-resistant genetically engineered crops approved for sale in the United States, 1994 to 2006

Crop

Glufosinate

Glyphosate

Bromoxynil

Sulfonylureas

Cotton

2004

1997

1994

Soybean

1996

1996

Ccanola

1995

1996

2000

Maize

1997

1998

Sugarbeet

1998

1999

Rye

1999

1999

Flax

1999

Rice

2006

Alfalfa

2005

Sources: Stephen O. Duke, “Taking Stock of Herbicide-Resistant Crops Ten Years after Introduction,” Pest Management Science 61 (2005): 211–218; Stephen O. Duke and Antonio L. Cerdeira, “Transgenic Crops for Herbicide Resistance,” chap. 3 in Transgenic Crop Plants, vol. 2, Utilization and Biosafety, ed. Chittaranjan Kole, Charles H. Michler, Albert G. Abbott, and Timothy C. Hall (Heidelberg: Springer, 2010), 134.

The developers of glyphosate-resistant crops announced the agricultural benefits of the herbicide prior to its commercial release: “Glyphosate has favorable environmental features such as rapid soil inactivation and degradation to natural products, little or no toxicity to important life forms, and minimum soil mobility.”9

Scientists at Monsanto heralded herbicide-resistance technology as a breeding mechanism that contributes to the sustainability of world agriculture through the use of high-quality and safe herbicides.10 Weed scientists largely supported the introduction of transgenic crops resistant to broad-spectrum, nonselective herbicides. During the 1990s, the two most popular herbicides approved in conjunction with herbicide-resistant crops were glyphosate and glufosinate.

The scientific work leading to the development of glufosinate dates back to the 1970s. The herbicide contains phosphinothricin, a chemical that kills plants by blocking a plant enzyme that is critical for nitrogen metabolism and for detoxifying ammonia, a by-product of plant metabolism. Herbicide-resistant glufosinate seeds contain a bacterial gene that encodes an enzyme that detoxifies phosphonothricin and protects the crop. Like glyphosate, glufosinate is a broad-spectrum herbicide that also kills fungi and bacteria. Table 5.1 shows the dates of approval of herbicide-resistant seeds for four herbicides from 1994 to 2006.

By 2013, 93 percent of all soybean acres, 85 percent of corn acres, and 82 percent of cotton acres were of herbicide-resistant (also referred to as herbicide-tolerant or HT) varieties. Public debates over herbicide-resistant crops raised the following questions: Do the transgenic HR crops provide added value to farmers (in the form of better yields and more income)? Do HR seeds require more or less use of herbicides? Does the use of HR crops spread weed resistance to herbicides? Are HR seeds used with toxicologically safe herbicides for humans and wildlife? Do HR crops improve or at least leave undiminished the ecosystems of both farms and surrounding areas?

On the question of yields, a USDA report stated: “The evidence on the impact of HT seeds on soybean, corn and cotton yields is mixed … several researchers found no significant difference between the yields of adopters and nonadopters of HT; some found that HT adopters had higher yields, while others found that adopters had lower yields.”11 The nonadopters may be using nontransgenic crops that are tolerant to selected herbicides. Yields have a lot to do with multiple factors. The most dependable studies require side-by-side plantings using the same herbicide with transgenic and nontransgenic crops.

In a comprehensive review of the scientific literature, Doug Gurian-Sherman, of the USDA and EPA but writing as a senior scientist for the Union of Concerned Scientists, concluded: “it does not appear that transgenic HT corn provides any consistent yield advantage over several non-transgenic herbicide systems … motivations other than increased yield are more likely to be encouraging farmers to adopt HT corn.”12 One comparative yield study by a group at the University of Nebraska found that the yields of glyphosate-tolerant cultivars were 5 percent lower than yields of the non-GMO sister cultivars. The authors surmised that the yield suppression in the GMO crops was related to the transgene or its insertion process, which raised doubts about the acclaimed yield gains from GMOs.13

A second contested issue is farmer return on investment. It has been widely reported that herbicide-resistant crops are associated with lower weed-control costs, especially compared to mechanical methods of weeding. Although there are some recognized cost savings in reduced weed management with HR crops, those are somewhat offset by higher prices for the seeds. The USDA study claims that there is a mixed effect on net returns. It argues that by reducing the time for weed management, farmers are able to work in other areas and even take on other jobs, which increases their net returns.14

Many claims and counterclaims have been made about whether HR crops reduce the use of herbicides. There is clearly a distinction between insect-resistant crops (which is discussed in chapter 7) and herbicide-resistant crops. The purpose of insect-resistant crops is to place the insect repellant in the plant rather than spraying it on the plant. But HR crops are designed to be used with herbicides. One claim is that the transgenic HR crops are more efficient and therefore require less herbicide use. Another claim is that transgenic HR crops are linked to a safer herbicide than nontransgenic crops. According to a USDA study by Jorge Fernandez-Cornejo, Seth Wechsler, Mike Livingston, and Lorraine Mitchell, “The adoption of HT [referred to as herbicide-tolerant rather than herbicide-resistant] crops has enabled farmers to substitute glyphosate for more toxic and persistent herbicides.”15

Studies have shown that for HR cotton and soybean, herbicide use (measured in pounds per acre) declined slightly in the first years and then increased. The USDA calls the increase “modest.”16 The USDA data suggest otherwise: “Herbicide use on corn by HT adopters increased from around 1.5 pounds per planted acre in both 2001 and 2005 to more than 2.0 pounds per planted acre in 2010, whereas herbicide use by nonadopters did not change much.”17 That is a hardly modest 30 percent increase. A suggested reason for the increase is that weeds became resistant to the primary herbicide—glyphosate. Nonadopters were more likely to diversify their management of weeds to stay on top of weed resistance. With integrated weed management, farmers utilize multiple strategies to control weeds. Those locked into the HR seeds increased their herbicide use in response to growing weed resistance. By 2014, seeds that were resistant to multiple herbicides with different modes of action (known as pyramiding or gene stacking) were approved. Enlist Duo seeds are resistant to glyphosate and 2,4-D.18 This was the industry’s response to the rise in weed resistance from a single herbicide.

Charles M. Benbrook, former executive director of the board of agriculture of the National Academy of Sciences, studied pesticide use in the United States during the growth of genetically modified crops. One part of his report covered herbicides and herbicide-resistant crops. He concluded that “HR crop technology has led to a 239 million kg (527 million pound) increase in herbicide use across the three major GE-HR crops, compared to what herbicide use would likely have been in the absence of HR crops. Well-documented increases in glyphosate applications per hectare of HR crop account for the majority of the 239 million kg increase.”19 His results are consistent with the finding that the spread of glyphosate-resistant weeds has led to increases in the use of glyphosate and other herbicides. Edward D. Perry, Federico Ciliberto, David A. Hennessy, and GianCarlo Moschini found that “Since 1998 the most striking trend has been an increase in the use of glyphosate.”20

Benbrook also found that glyphosate application has risen nearly fifteen-fold since Roundup Ready crops were first introduced in 1996 and that transgenic HT crops account for about 56 percent of the global use of glyphosate.21

Do HR crops contribute to weed resistance? The consensus viewpoint is that the monolithic continuous uses of a single herbicide will eventually contribute to weed resistance. This was predicted in 1996 at the dawn of the revolution in transgenic crops: “The widespread use of HRCs developed for resistance to single herbicides will accelerate the selection pressure on weeds to evolve resistant biotypes.”22 And these resistant biotypes have to be able to reproduce with their fitness to survive unaffected.

This prediction is particularly relevant with development of glyphosate resistance at a global scale as shown in the number of weed species across the globe that have developed glyphosate resistance over two decades (figure 5.1).

Figure 5.1

Global increases in glyphosate-resistant weeds.

Source: Weedscience.org, International Survey of Herbicide-Resistant Weeds, http://www.weedscience.org/summary/resistbyactive.aspx.

The next generation of HR crops is being developed with stacked resistance to multiple modes of herbicide action into a single seed. As Jerry M. Green has noted, “Combining herbicide mixtures with multiple-resistant (MR) varieties can reduce reliance on a single MOA [mode of action].”23

Have HR crops been developed with the safest herbicides available? This was certainly one of its early appeals. Because the most prevalent herbicide in current use is glyphosate, scientists have asked whether glyphosate is the safest broad-spectrum herbicide that could be used for HR crops and whether its level of safety is safe enough. One way to document toxicity is by oral LD50 values, which is the amount of the chemical required to give a lethal dose to the test animal population, usually mice. Scientists at the Institute of Food and Agricultural Sciences at the University of Florida compared the oral LD50 of several commonly used pesticides (the lower the lethal dose, the higher the toxicity): paraquat ~100; triclopyr 630; 2,4 D 666; pendamethalin 1,050; atrazine 3,090; glyphosate 4,900; imazaquin >5,000.24 On the LD50 criteria, glyphosate comes out fairly well.

Other toxicological criteria include whether the substance is a carcinogen, neurotoxin, mutagen, or endocrine disruptor. Also to be considered are the formulations for glyphosate, which includes adjuvants that amplify permeability and increase toxicity. Roundup Ultra, the glyphosate herbicide for Roundup Ready crops, contains 41% of glyphosate and 59% of other ingredients.25 A 2009 study confirms that the adjuvants for Roundup (a trade variety of glyphosate) can sometimes be more toxic to organisms than the active ingredient: “adjuvants in Roundup formulations are not inert. Moreover, the proprietary mixtures available on the market could cause cell damage and even death around residual levels to be expected, especially in food and feed derived from R formulation-treated crops [that is, POEA].”26 A follow-up study by Nicolas Defarge and his colleagues looked at the effects of glyphosate’s active ingredient and adjuvant chemicals on human cells: “Briefly, all co-formulants inhibited aromatase and disrupted mitochondrial respiration (and membranes) at higher concentrations. APG and POEA were 15–18 times and 1200–2000 times more cytotoxic than G, respectively.”27

There are also environmental criteria. How does the herbicide compare with other herbicides with respect to their environmental effects on nontarget plants and animal species? Comparative evaluations of herbicides for environmental effects are rarely definitive. The decline of the Monarch butterfly has spurred studies on whether herbicides are one of its causes, and glyphosate has been identified as a major suspect:28 “Given the established dominance of glyphosate-tolerant crop plants and widespread use of glyphosate herbicide, the virtual disappearance of milkweeds from agricultural fields is inevitable. Thus, the resource base for Monarchs in the Midwest will be permanently reduced.”29

Although glyphosate—compared in all categories to 2,4-D, atrazine, and bromoxynil—has traditionally come out as safer, that conclusion was brought into question when the International Agency for Research on Cancer reclassified glyphosate as a probable human carcinogen.30 Recent studies have established new evidence questioning the safety of glyphosate: “Research has now established that glyphosate can persist in the environment, and therefore, assessments of the health risks associated with glyphosate are more complicated than suggested by acute toxicity data that relate primarily to accidental high-rate exposure … chronic glyphosate exposure at low concentrations can potentially result in risks to human health.”31

The toxicity of glyphosate-based herbicides must be understood through the different formulations of the active ingredient, some of which contain toxic adjuvants that are reputed to have a higher toxicity than pure glyphosate.32

The final word on the toxicology of glyphosate has no direct bearing on the safety of the herbicide-resistant-glyphosate seed. But it does raise the question about a popular seed class that is inextricably tied to the use of a particular herbicide formulation that has become increasingly suspect and the target of scores of lawsuits.

Notes

1.  Luca Lombardo, Gerardo Coppola, and Samanta Zelasco, “New Technologies for Insect-Resistant and Herbicide Tolerant Plants,” Trends in Biotechnology 34, no. 1 (2016): 49–57.

2.  Charles A. Hamner and Harold B. Tukey, “The Herbicidal Action of 2,4 Dischlorophenoxyacetic and 2,4,5 Trichlorophenoxy Acetic Acid on Bindweed,” Science 100, no. 2590 (1944): 154–155.

3.  Rachel Carson, Silent Spring (New York: Houghton Mifflin, 1962, 1994).

4.  Barbara J. Mazor and S. Carl Falco, “The Development of Herbicide Resistant Crops,” Plant Physiology and Plant Molecular Biology: Annual Reviews 40 (1989): 443.

5.  Martin Paul Krayer von Krauss, Elizabeth A. Casman, and Mitchell J. Small, “Elicitation of Expert Judgments of Uncertainty in the Risk Assessment of Herbicide-Tolerant Oilseed Crops,” Risk Analysis 24, no. 6 (2004): 1523.

6.  Charles M. Benbrook, “Trends in Glyphosate Herbicide Use in the United States and Globally,” Environmental Science Europe 28, no. 3 (2016): 1–15.

7.  Jorge Fernandez-Cornejo, Seth Wechsler, Mike Livingston, and Lorraine Mitchell, “Genetically Engineered Crops in the United States,” Economic Research Report No. 162, Economic Research Service, U.S. Department of Agriculture, February 2014, p. 6, www.ers.usda.gov/media/1282246/err162.pdf.

8.  Benbrook, “Trends in Glyphosate Herbicide Use in the United States and Globally.”

9.  Ganesh M. Kishore, Stephen R. Padgette, and Robert T. Fraley, “History of Herbicide-Tolerant Crops, Methods of Development and Current State of the Art: Emphasis on Glyphosate Tolerance,” Weed Technology 6 (1992): 628.

10.  Kishore, Padgette, and Fraley, “History of Herbicide-Tolerant Crops.”

11.  Fernandez-Cornejo et al., “Genetically Engineered Crops in the United States,” 16.

12.  Doug Gurian-Sherman, “Failure to Yield: Evaluating the Performance of Genetically Engineered Crops,” Union of Concerned Scientists, Cambridge, MA, April 2009, 17.

13.  Roger W. Elmore, Fred W. Roeth, Lenis A. Nelson, Charles A. Shapiro, and Robert N. Klein, “Glyphosate-Resistant Soybean Cultivar Yields Compared with Sister Lines,” Agronomy Journal 93 (2001): 408–412.

14.  Fernandez-Cornejo et al., “Genetically Engineered Crops in the United States,” 22.

15.  Fernandez-Cornejo et al., 6.

16.  Fernandez-Cornejo et al., 24.

17.  Fernandez-Cornejo et al., 24.

18.  Environmental Protection Agency, “Registration of Enlist Duo,” https://www.epa.gov/ingredients-used-pesticide-products/registration-enlist-duo.

19.  Charles M. Benbrook, “Impact of Genetically Engineered Crops on Pesticide Use in the U.S.: The First Sixteen Years,” Environmental Sciences Europe 24 (2016): 7.

20.  Edward D. Perry, Federico Ciliberto, David A, Hennessy, and GianCarlo Moschini, “Genetically Engineered Crops and Pesticide Use in U.S. Maize and Soybeans,” Science Advances 2, no. 8 (2016).

21.  Benbrook, “Impact of Genetically Engineered Crops on Pesticide Use in the U.S.,” 1.

22.  Sheldon Krimsky and Roger Wrubel, Agricultural Biotechnology and the Environment (Chicago: University of Illinois Press, 1996), 47.

23.  Jerry M. Green, “The Benefits of Herbicide Resistant Crops,” Pest Management Science 68 (2012): 1323–1331.

24.  Fred Fishel, Jason Ferrell, Greg MacDonald, and Brent Sellers, “Herbicides: How Toxic Are They?,” Document PI-133, UF/IFAS Extension, Institute of Food and Agricultural Sciences, University of Florida, September 2006, rev. February 2013, https://edis.ifas.ufl.edu/pi170.

25.  Sales sheet for Roundup Ready, Monsanto Company, St. Louis, MO, http://www.cdms.net/LDat/ld178006.pdf.

26.  Nora Benachour and Giles-Eric Séralini, “Glyphosate Formulations Induce Apotosis and Necrosis in Human Umbilical, Embryonic, and Placental Cells,” Chemical Research in Toxicology 22, no. 1 (2009): 97–105.

27.  Nicolas Defarge, Eszter Takács, Verónica Laura Lozano, Robin Mesnage, Joël Spiroux de Vendômois, Gilles-Eric Séralini, and András Székács, “Co-formulants in Glyphosate-Based Herbicides Disrupt Aromatase Activity in Human Cells below Toxic Levels,” International Journal of Environmental Research in Public Health 13, no. 3 (2016): 264.

28.  Wes Maxwell, “Monsanto’s Glyphosate Wiping out Monarch Butterflies; Population down 74 Percent in California,” Natural News, July 26, 2016, https://www.naturalnews.com/054775_monarch_butterflies_milkweed_glyphosate.html.

29.  John M. Pleasants and Karen S. Oberhauser, “Milkweed Loss in Agricultural Fields Because of Herbicide Use: Effect on the Monarch Butterfly Population,” Insect Conservation and Diversity 6 (2013): 135–144.

30.  International Agency Research on Cancer (IARC), “Glyphosate,” in Some Organophosphate Insecticides and Herbicides, vol. 112 of the IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, World Health Organization, August 11, 2016, http://monographs.iarc.fr/ENG/Monographs/vol112/mono112-10.pdf.

31.  Shahla Hosseini Bai and Steven M. Ogbourne, “Glyphosate: Environmental Contamination, Toxicity and Potential Risks to Human Health via Food Contamination,” Environmental Science and Pollution Research 23, no. 19 (2016): 18,988–19,001.

32.  Robin Mesnage, George Renney, Gilles-Eric Séralini, Malcolm Ward, and Michael N. Antoniou, “Multiomics Reveal Non-alcoholic Fatty Liver Disease in Rats Following Chronic Exposure to an Ultra-low Dose of Roundup Herbicide,” Nature Scientific Reports 7 (2017): 39,328–39,343.