Crops That Shut Down Pests' Genes

By Katherine Bourzac
Technology Review
November 5, 2007

Researchers have created plants that kill insects by disrupting their gene expression. The crops, which initiate a gene-silencing response called RNA interference, are a step beyond existing genetically modified crops that produce toxic proteins. Because the new crops target particular genes in particular insects, some researchers suggest that they will be safer and less likely to have unintended effects than other genetically modified plants. Others warn that it is too early to make such predictions and that the plants should be carefully tested to ensure that they do not pose environmental problems. But most researchers agree that it's unlikely that eating these plants would have adverse effects on humans.

RNA interference occurs naturally in animals ranging from worms to humans. It's a process whereby double-stranded RNA copies of specific genes prevent cells from translating those genes into proteins. The new genetically modified plants carry genes for double-stranded RNA targeted to particular insect genes. Two papers published concurrently in Nature Biotechnology this week show that in some insects, eating double-stranded RNA is enough to cause gene silencing. This is surprising: in previous research, RNA interfered with organisms' gene expression only when it was injected.

"People have been trying this, but there have been no reports of success before," says Karl Gordon, a research scientist in entomology at the Commonwealth Scientific and Industrial Research Organisation, in Canberra, Australia. The recent work, he says, is the first to demonstrate the promise of RNA interference as a means of pest control.

Researchers at the Chinese Academy of Sciences, in Shanghai, made cotton plants that silence a gene that allows cotton bollworms to process the toxin gossypol, which occurs naturally in cotton. Bollworms that eat the genetically engineered cotton can't make their toxin-processing proteins, and they die. Researchers at Monsanto and Devgen, a Belgian company, made corn plants that silence a gene essential for energy production in corn rootworms; ingestion wipes out the worms within 12 days.

The most effective genetic approach to pest control has been to make plants that produce a protein called Bt toxin, which causes insects to slow down, then stop eating crops, then die. More than 120,000 square miles of crops genetically engineered to produce Bt were grown last year. But Bt isn't effective against many pests, including corn rootworm, which can cause such extensive damage to corn plants' root systems that the plants blow over in the wind. And researchers are concerned that insect pests are becoming resistant to Bt.

"We need a way to come around resistance to Bt," says Abhaya Dandekar, professor of pomology at the University of California, Davis. RNA interference is attractive, he says, because insects are unlikely to become resistant to it. "The only way to go around RNA interference is to shut down the whole system." What he means is that the new plants take advantage of a gene-silencing mechanism that the insects' bodies already use: RNA interference is thought to be a critical part of insects' and other animals' immune systems. Insects that shut down RNA interference in order to safely eat genetically engineered plants would probably get sick, says Dandekar.

Another drawback to Bt is its nonspecificity. The toxin may have what are called off-target effects: it can kill insects that pose no threat to crops.

RNA interference, says Ty Vaughn, a researcher at Monsanto, "can be species specific," allowing for "a higher level of control." Other researchers agree and say that Monsanto has, so far, demonstrated a high level of specificity. "They should be able to avoid nonspecific, off-target effects," says Gordon.

But other researchers warn against jumping to that conclusion too soon. "RNA interference to control pests is an interesting idea, but it's important to understand the ecology," says Bernard Mathey-Prevot, director of the Drosophila (fruit fly) RNA Interference Screening Center at Harvard Medical School. "It's very hard to know in advance whether other insects might be targeted."

In addition to killing nonpest insects, Mathey-Prevot says, the gene-silencing mechanism could spread between different species of plant, or from plants to other organisms, such as bacteria in the soil. Such spread might be harmless, but then again, it might not. "We need to understand it a little bit more," Mathey-Prevot says.

Vaughn says that the research is in its early stages and that Monsanto has not set a timeline for bringing gene-silencing crops to the market. Monsanto will put its new transgenic corn "through a battery of tests" to establish that its effects are specific to corn rootworms, he says. Tobacco cutworms that ingested the corn did not seem to be affected.

But to prove conclusive, researchers say, such testing would have to be arduous. "You would have to anticipate all the species you wouldn't want it to affect" and then test them, says David Root, project leader of the RNA Interference Consortium at the Broad Institute, Harvard and MIT's jointly operated center for research on genomic medicine. And Gordon anticipates that regulatory agencies will demand broad screening.

Although humans have genes similar to insect genes, researchers say that it is highly unlikely that ingesting Monsanto's corn would cause gene silencing in people. "If you fed tons of it to a mouse, I don't think you'd get anywhere," says Root. RNA "just gets digested" by mice and humans.

The U.S. government does not require the labeling of foods containing genetically modified organisms, but it does require safety testing. Fred Gould, professor of agriculture at North Carolina State University, says that because the new crops produce what's effectively a pesticide, they would be regulated by the U.S. Environmental Protection Agency. Such foods must be tested both in animals and through exposure to what Gould calls "reconstituted human stomach juices."

It's also unclear how widely applicable the use of RNA interference as a pesticide will be. In many insects, ingestion of RNA may not cause gene silencing. But cotton bollworms and corn rootworms are major agricultural pests, feeding on two of the most widely grown crops in the world. Even if RNA interference is helpless against any other insects, it could still have a major impact on agriculture.

Mathey-Prevot counsels patience. At this point, he says, it's too early to make claims about the safety of the technique. But, he says, that also means it's too early to conclude that the ability to cause RNA interference is any more dangerous than current genetic modifications of food crops.

Do Escaped Transgenes Persist in Nature?

BY S. I. Warwick, A. Légère, M.-J. Simard, T. James
Molecular Ecology (OnlineEarly Articles)
November 2007

Abstract

The existence of transgenic hybrids resulting from transgene escape from genetically modified (GM) crops to wild or weedy relatives is well documented but the fate of the transgene over time in recipient wild species populations is still relatively unknown. This is the first report of the persistence and apparent introgression, i.e. stable incorporation of genes from one differentiated gene pool into another, of an herbicide resistance transgene from Brassica napus into the gene pool of its weedy relative, Brassica rapa, monitored under natural commercial field conditions. Hybridization between glyphosate-resistant [herbicide resistance (HR)] B. napus and B. rapa was first observed at two Québec sites, Ste Agathe and St Henri, in 2001. B. rapa populations at these two locations were monitored in 2002, 2003 and 2005 for the presence of hybrids and transgene persistence. Hybrid numbers decreased over the 3-year period, from 85 out of ~200 plants surveyed in 2002 to only five out of 200 plants in 2005 (St Henri site). Most hybrids had the HR trait, reduced male fertility, intermediate genome structure, and presence of both species-specific amplified fragment length polymorphism markers. Both F1 and backcross hybrid generations were detected. One introgressed individual, i.e. with the HR trait and diploid ploidy level of B. rapa, was observed in 2005. The latter had reduced pollen viability but produced ~480 seeds. Forty-eight of the 50 progeny grown from this plant were diploid with high pollen viability and 22 had the transgene (1:1 segregation). These observations confirm the persistence of the HR trait over time. Persistence occurred over a 6-year period, in the absence of herbicide selection pressure (with the exception of possible exposure to glyphosate in 2002), and in spite of the fitness cost associated with hybridization.

Low-Dose Exposure and Immunogenicity of Transgenic Maize Expressing the Escherichia Coli Heat-Labile Toxin B Subunit

By Beyer AJ, K Wang, AN Umble, JD Wolt and JE Cunnick
Environmental Health Perspectives 115(3):354-360
November 8, 2007

Minute quantities of a bacterial protein inserted in corn provoke immune reactions in mice. The protein is added to increase the effectiveness of plant-based transgenic vaccines. The results indicate that special care will be needed with transgenic corn to reduce exposure to workers and the public if this protein is used commercially in corn or other food crops, to avoid unwanted immune responses in people and decreased effectiveness of oral vaccines that use the protein.

What does it mean? Eating extremely small amounts of LT-B several times over less than a month caused exposed mice to develop immune reactions to the protein. LT-B is being tested in transgenic crops to increase effectiveness of oral vaccines. Unless unintentional exposure is prevented, widespread production of LT-B could sensitize the public and workers to the protein.

Special handling of transgenic corn or other crops used to produce LT-B enhanced vaccines may be necessary to prevent repeated low-level exposure. People inadvertently exposed to LT-B could develop allergies to other food proteins eaten at the same time. Frequent exposure could possibly interfere with the effectiveness of LT-B based vaccines as well.

In the study, approximately half of the rodents exposed to 0.02 mcg (20 nanograms) of LT-B orally, three times over 21 days, demonstrated immune priming. Humans are roughly 7,500 times the size of these 20-gram mice. If people react the same as mice, the equivalent dose of LT-B for a 150-pound (70 kilogram) person would be about 150 millionths of a gram. This is a small amount.

The results in the mice were produced by only a few intermittent doses. Workers could be exposed daily to much larger doses in grain dusts. Population risks would depend upon the likelihood of seed contamination or cross-pollination by LT-B crops to food crops grown in nearby fields. Barring other considerations, transgenic plants would usually be grown outside in large fields to reduce costs. Given the remarkably low dose of LT-B required for immune responses, careful studies are needed to determine if such production strategies are worth the risks of population wide exposure and possible immune system effects.

Synopsis by Rick Stahlhut, Ph.D. and Wendy Hessler

Paraguay: The Dark Side of the Soy Boom

By David Vargas
Inter Press Service
November 8, 2007

ASUNCION, Nov 8 (IPS) - A sea of green stretches as far as the eye can see on both sides of the dirt road leading to the communities of Lima, Capiibary and Guayaibí, 250 km from the capital, in the northern Paraguayan department (province) of San Pedro, one of the country's poorest.

The huge fields are planted with genetically modified soy, Paraguay's leading export product. But as it takes over more and more land, the crop is leaving sick people, displaced communities and trampled rights in its wake, according to the documentary "Soberania violada" (Violation of Sovereignty).

The documentary, produced by a Paraguayan team, portrays the drama of campesino (small farmer) communities that experience the spread of soy plantations as a threat to their survival.

"The economic interests of large landowners -- most of them foreigners -- and multinational corporations are destroying entire communities, felling forests, polluting streams and rivers, making children sick, causing miscarriages, killing campesinos and forcing them to abandon their land and their culture," says the synopsis of the 40-minute documentary.

Paraguay has become the world\u2019s fourth largest exporter of soy, after the United States, Brazil and Argentina. According to the Agriculture Ministry, soy is grown on 2.4 million hectares of land and accounts for 38 percent of the country\u2019s agricultural production.

The Paraguayan Chamber of Cereals and Oilseeds Exporters (CAPECO) announced that their goal for 2008 is to expand soy cultivation to four million hectares and to double export revenues from the commodity, which in the first quarter of 2007 amounted to 780 million dollars.

But that figure fails to reflect the social and environmental consequences of the expansion of soy cultivation, which are reflected in the documentary through dozens of testimonies from campesinos.

"The idea for the film came from the provincial Coordinating Committee for the Defence of Sovereignty, an umbrella group for representatives of organisations and leaders of different communities in San Pedro," Arturo Peña, one of the producers of the documentary, told IPS.

"Soberanía violada" has been included on the programme of the One World Berlin Film Festival to be held this month in the German capital, where it is due to be screened on Nov. 18.

The filmmaking team\u2019s general coordinator was Catalina Servín, and the documentary was written, directed and filmed by Malu Vázquez and edited by José Elizeche, with music by W. Krauch.

Their aim, they said, was to create a tool that could be used to raise awareness on the problem, which has got worse over the last five years as transgenic soy has expanded in the area.

"Thousands of families have already left the province after selling their land, usually because they were surrounded by the soy crops and endangered by the spraying of toxic agrochemicals. They had no choice," said Peña.

The soybean boom has also brought unemployment. It requires little labour, and in the east of Paraguay soy has displaced cotton, which used to employ large numbers of people, the documentary says.

Small farmers, who make up a large proportion of the country\u2019s six million people, have been displaced by large-scale soy producers.

According to a study by the non-governmental social research organisation Base-IS, 70 percent of Paraguay\u2019s farmland is presently in the hands of foreign landowners, who are mainly Brazilian.

Some small farmers, however, have refused to budge. One example is Manuel Cuevas, who has cultivated beans, maize and other subsistence products near the village of Lima for 30 years. His 10-hectare property is surrounded by Brazilian-owned soy fields.

Cuevas has received several offers for his land, but he and his family have turned them all down. "So far we\u2019re doing alright," he says in a resigned tone of voice.

"I will never leave. I have everything I need here: land, running water, electricity. There is no reason for me to leave my land," says Reinaldo Casco, another farmer, who adds proudly that his parents were among Lima\u2019s first settlers.

"These are just two testimonies out of the dozens shown in the documentary, which reflect the abandoned state of these rural villages, left to fend for themselves for decades, with obsolete health systems, authorities who serve the interests of the big landowners, and roads in terrible condition," Peña told IPS.

"And now they are also threatened by the crushing advance of the agroexport model," he said.

Sociologist Tomás Palau, one of the authors of the book "Los refugiados del modelo agroexportador" (Agroexport Refugees), described the main effects of the rise of soy monoculture on rural communities.

"There is strong pressure on the campesinos\u2019 land, because the market value has sky-rocketed," he told IPS.

The campesinos are displaced in various ways: their land is bought or leased, or they are forced to leave because of massive spraying with agrochemicals.

"There are also armed groups operating in the area. It's really an eviction army," he said.

Spraying with toxic agrochemicals has negative effects on both human and animal health, "causing illnesses ranging from allergies and respiratory problems to cancer, foetal malformation and miscarriage," Palau said.

The environment also suffers. "The agrotoxics poison rivers and the earth, kill microorganisms in the fertile layers of soil and increase deforestation," he said.

But according to Palau, the least visible aspect of soy agribusiness is the fact that the revenues from soy exports do not remain within the country, because they belong to large foreign producers and corporations.

"Without realising it, we're finding ourselves in a situation where an extremely high percentage of Paraguayan exports is controlled by three or four multinational corporations: Monsanto, which supplies seeds to 90 percent of the producers, and companies like Cargill, Louis Dreyfus and ADM (Archer Daniels Midland)," he said.

Soy cultivation in Paraguay began to expand in the mid-1960s and boomed in the late 1990s with the introduction of genetically modified seeds by companies such as Monsanto.

Intensive soy production has caused a fall in traditional activities like timber extraction, cattle ranching and even production of cotton, which used to be the country\u2019s main agricultural export. The area under cotton cultivation has dropped from 509,000 hectares in 1990 to only 160,000 hectares in 2006.

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