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Transgenic moths on the horizon

New technology developed to combat the main threat to maize crops

The fall armyworm (Spodoptera frugiperda) is responsible for losses of up to 50% on maize farms

Produtora São Paulo / Oxitec

Brazilian farmers will soon be able to use a new tool to combat what is considered by agribusiness as maize farming’s worst pest. The company Oxitec do Brasil is preparing for the commercial launch of its genetically modified moth, which can be released in maize fields to combat the fall armyworm (Spodoptera frugiperda). The armyworm is found in every maize-growing region of Brazil and can cause crop losses of up to 50%. In 2021, Oxitec’s transgenic moth, called Spodoptera do Bem, was granted approval by Brazil’s National Biosafety Commission (CTNBio), the office of the Ministry of Science, Technology, and Innovation (MCTI) responsible for authorizing the release of genetically modified organisms in Brazil.

“Spodoptera do Bem is a safe and effective product”, says geneticist Natalia Ferreira, executive director at Oxitec do Brasil. “We are in the phase of engaging farmers, talking to distributors, and continuing with trials on farms to understand how the product fits into the agricultural producer’s routine,” she explains. The company says that the product’s commercial launch will take place within the next few years.

Spodoptera do Bem is the commercial name of the genetically modified OX5382G strain, developed by the original company in the UK and tested on two Brazilian farms, one in Mato Grosso and another in São Paulo. Oxitec was founded in 2002 as a spinoff from the University of Oxford and is now a subsidiary of the American company Third Security, based in Virginia.

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Brazil is the first and only country in the world to release transgenic moths into the field. The genetically modified version of the fall armyworm carries two different genes that were introduced in the laboratory. One of these genes, known as tTAV, prevents the development of females so that only males hatch from the eggs of the next generation, drastically affecting the insect’s ability to reproduce.

“In the lab, we improved a gene that already exists in Spodoptera and other insects and arachnids, inserting a promoter [a specific DNA sequence] that tells the cell to produce a lot of that gene,” said Ferreira. “It’s like an overdose. Like if instead of producing organ cells, my entire body started producing only collagen,” he says. “The result is that I would no longer produce blood, saliva, or anything needed to sustain my life; I would die due to a lack of these substances.”

The second inserted gene, DsRed2, is a marker derived from a species of marine coral that produces a fluorescent protein, helping to distinguish modified animals from wild insects.

The technique for combating the pest consists of releasing genetically modified males into the field to breed with wild females. These pairings only produce male larvae, which after the pupal stage become moths carrying the self-limiting gene in their DNA that in the future will again prevent any female offspring from being born. Thus, within a few generations, the insect population will significantly decrease, according to the company.

The same technology is used in Aedes do Bem, sold by the company in Brazil since 2021 to reduce Aedes aegypti mosquito populations. The objective is to reduce cases of dengue and other diseases transmitted by mosquitoes, such as Zika and Chikungunya. The small group of transgenic animals approved for sale in Brazil by CTNBio includes the modified Spodoptera, two versions of Aedes aegypti created by Oxitec, and a salmon developed by the Canadian company AquaBounty.

Eduardo Cesar / Revista Pesquisa FAPESPAs well as maize, the moth feeds on some 50 other plant varietiesEduardo Cesar / Revista Pesquisa FAPESP

Maria Lúcia Zaidan Dagli, a veterinarian from the Experimental and Comparative Oncology Laboratory at the School of Veterinary Medicine and Zootechnics of the University of São Paulo (FMVZ-USP) and a member of CTNBio, sees the release of Spodoptera do Bem in Brazil as a positive move. She was involved in the decision to approve Oxitec’s first version of Aedes aegypti.

Dagli explains that to be authorized for sale by CTNBio, a product must be approved by the agency’s four sectors, which verify its impact on humans, animals, plants, and the environment, certifying that it is safe based on data and studies presented by the applicant company. After approval is granted, the product is monitored closely for five years, during which time the company has to submit annual reports to CTNBio.

“It’s the same process that takes place with new drugs released by other regulatory agencies. If a problem is reported, depending on the severity, sale of the product may be suspended,” underscores the researcher. She points out, however, that no CTNBio-approved product has ever been suspended.

There are approximately 200 chemicals available on the market in Brazil to help farmers combat the fall armyworm, according to the Brazilian Agricultural Research Corporation (EMBRAPA). However, Spodoptera has demonstrated resistance to conventional insecticides. There is also concern about the unwanted effects these pesticides may have on the health of nontarget organisms and the environment.

In addition to insecticides, there are nine biological products registered in the country and another four soon to be launched. Transgenic maize that expresses proteins from the bacterium Bacillus thuringiensis (Bt) to kill larvae has also been used since the 2008/2009 harvest. However, the insects already show resistance to the modified crop.

“When we use insecticides or transgenic plants to control a pest, we end up involuntarily selecting individuals capable of surviving these technologies in the wild,” explains Alberto Soares Corrêa, head of the Molecular Ecology of Arthropods Laboratory at USP’s Luiz de Queiroz College of Agriculture (ESALQ). “A single female Spodoptera frugiperda can lay up to 1,500 eggs in its life cycle. It’s an extremely complex species to address due to its polyphagy [ability to feed on different plant species] and dispersal capacity. Native to the Americas, it has recently become a cosmopolitan pest with reports of its detection in countries in Africa, Asia, Europe, and Oceania,” says Corrêa.

To delay the insect’s resistance to transgenic maize, farmers are advised to reserve some land — between 10% and 20% of the crop, although there is no consensus on the exact area — for the cultivation of conventional, nontransgenic plants, known as a refuge. The idea is that the resistant moths will breed with those from the refuge that do not have the alleles (different forms of a given gene) that confer protection. “The problem is that farmers often do not bother planting a refuge area, and as a result, the insects develop resistance faster,” says the ESALQ researcher.

According to Oxitec, transgenic Spodoptera frugiperda is a highly effective method of controlling resistance to Bt maize. “Spodoptera do Bem has never seen insecticides, it has never seen Bt in its life, it’s totally susceptible,” explains Ferreira. “When transgenic males on a farm mate with nonmodified females, any male descendants inherit the part of the father’s genome that does not provide resistance. The effect of all insecticides, pesticides, and Bt maize is thus restored. This is a technology that will allow farmers to use less pesticide and to recover or extend the lifespan of biotechnological seeds.”

Produtora São Paulo/OxitecOxitec employees in the field conducting a pilot study of Spodoptera do BemProdutora São Paulo/Oxitec

Corrêa explains that autocide — when a genetically modified insect is used to control the population of a species through breeding — is an old technique. “The classic example is the screw-worm fly [Cochliomyia hominivorax], which was eradicated in the United States after millions of sterile insects were released starting in the 1950s,” he says.

The important difference is that instead of transgenic versions, males rendered sterile by gamma-ray irradiation were released. It is hoped that the use of transgenic insects will overcome some of the previous method’s weaknesses, at least initially. “Exposure to radiation can harm the insects in various ways, impacting their biological characteristics and behavior, which can make the strategy less successful. The idea is that with transgenic insects, individuals can better compete with wild males, mating with more females that do not produce any offspring, reducing the population of the target species.”

Corrêa is reluctant to speculate on the risks and potential ecological consequences of releasing a transgenic insect into nature. “There are no scientific data available in the literature to answer the biggest questions. This has never been done before on a large scale,” says the researcher. “In the case of Spodoptera frugiperda, if CTNBio approved it, then they must believe it meets the minimum safety criteria for the technology to be applied.”

He notes that the same questions arose with transgenic plants. “Today, we know that they are extremely safe. Thus, their use has expanded worldwide. With animals, however, there is a large difference in reproductive and biochemical issues and with regard to genome structure. We can’t simply say: it worked with transgenic plants, so it’ll work with transgenic animals.”

Biologist José Maria Gusman Ferraz, a visiting researcher at the Laboratory of Ecological Engineering of the University of Campinas (UNICAMP), studied Spodoptera frugiperda during his PhD. He sees the new technology as adding another string to the bow to help fight the pest but has doubts about its efficiency, since adult fall armyworms can travel long distances and maize is generally planted in large open areas. “The history of this type of technology is that it only works well in isolated areas, like islands,” he says.

Ferraz would also like to see more data on possible damage to parasitoids (the moth’s natural enemies) and the risks of transgenic DNA remaining in the environment. “New technologies can work in a short time frame, but they can also have negative effects and then stop working,” he points out. “The basic principle of life is diversity, and when we reduce that diversity, the system becomes fragile.”

Another advantage of genetically modified organisms (GMOs) over irradiated organisms is practicality and cost, explains Margareth Capurro, a biochemist from USP’s Institute of Biomedical Sciences (ICB) and technical coordinator of a study on transgenic Aedes mosquitos carried out in Bahia. According to Capurro, 44 countries are preparing to release sterile males to control insect populations, although no other countries are using GMOs to do so.

“For sterile males, all you need is to set up a biofactory and pay ongoing production costs; for transgenic insects, you need to pay the company that manufactures them. Transgenic versions, however, make life easier because they eliminate the need for equipment that costs between one and two hundred thousand dollars. How would you have an irradiator in every state in Brazil?” she asks. “It’s not feasible. The logistics of the sterilized male Aedes aegypti mosquitos requires that they be produced near the irradiator and transported and released within 24 hours.”

One difference between the screw-worm fly eradicated from the United States last century and Spodoptera frugiperda is that the former is monogamous — females mate only once and with only one male. The latter can breed multiple times. Unlike Aedes aegypti, which is an exotic mosquito from the region of Egypt, the fall armyworm is native to the American continent. In addition to attacking maize, Spodoptera also causes problems for other important crops, such as cotton, soy, wheat, rice, and beans. It feeds on approximately 50 plant varieties from more than 20 botanical families, according to EMBRAPA data.

To eradicate the pest, a public policy would be needed that would promote action across the national territory and even in neighboring countries of the American continent. “Brazil is an enormous country with an extremely long border. We have problems uniting government agencies, companies, and farmers to implement pest monitoring and control strategies,” ponders Corrêa. “Eradicating the pest in Brazil would be practically impossible. I don’t think that is the company’s objective.”

Scientific article
REAVEY, C. E. et al. Self-limiting fall armyworm: A new approach in development for sustainable crop protection and resistance management. BMC Biotechnology. jan. 27, 2022.