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Crops That Shut Down Pests’ Genes

Monsanto is developing genetically modified plants that use RNA interference to kill the insects that eat them.

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.

Corn that bites back: Genetically modified corn made by Monsanto silences genes in the insects that eat its roots, slowing and eventually killing them. The normal corn root system on the left has been nibbled by corn rootworm; the hardy root system on the right is from a genetically modified corn plant.

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.

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