By Andrew Pollack, The New York Times, January 27, 2014
|Monsanto is exploring the use of RNA interference to kill a mite that plays a role in bee die-off. Photo: Monsanto|
Scientists and biotechnology companies are developing what could become the next powerful weapon in the war on pests — one that harnesses a Nobel Prize-winning discovery to kill insects and pathogens by disabling their genes.
By zeroing in on a genetic sequence unique to one species, the technique has the potential to kill a pest without harming beneficial insects. That would be a big advance over chemical pesticides.
“If you use a neuro-poison, it kills everything,” said Subba Reddy Palli, an entomologist at the University of Kentucky who is researching the technology, which is called RNA interference. “But this one is very target-specific.”
But some specialists fear that releasing gene-silencing agents into fields could harm beneficial insects, especially among organisms that have a common genetic makeup, and possibly even human health. The controversy echoes the larger debate over genetic modification of crops that has been raging for years. The Environmental Protection Agency, which regulates pesticides, will hold a meeting of scientific advisers on Tuesday to discuss the potential risks of RNA interference.
“To attempt to use this technology at this current stage of understanding would be more naïve than our use of DDT in the 1950s,” the National Honey Bee Advisory Board said in comments submitted to the E.P.A. before the meeting, at the agency’s conference center in Arlington, Va.
RNA interference is of interest to beekeepers because one possible use, under development by Monsanto, is to kill a mite that is believed to be at least partly responsible for the mass die-offs of honeybees in recent years.
Monsanto has applied for regulatory approval of corn that is genetically engineered to use RNAi, as the approach is called for short, to kill the western corn rootworm, one of the costliest of agricultural pests. In another project it is trying to develop a spray that would restore the ability of its Roundup herbicide to kill weeds that have grown Some bee specialists submitted comments saying they would welcome attempts to use RNAi to save honeybees. Groups representing corn, soybean and cotton farmers also support the technology.
“Commercial RNAi technology brings U.S. agriculture into an entirely new generation of tools holding great promise,” the National Corn Growers Association said.
Corn growers need a new tool. For a decade they have been combating the rootworm by planting so-called BT crops, which are genetically engineered to produce a toxin that kills the insects when they eat the crop.
Or at least the toxin is supposed to kill them. But rootworms are now evolving resistance to at least one BT toxin.
RNA interference is a natural phenomenon that is set off by double-stranded RNA.
DNA, which is what genes are made of, is usually double stranded, the famous double helix. But RNA, which is a messenger in cells, usually consists of a single strand of chemical units representing the letters of the genetic code.
So when a cell senses a double-stranded RNA, it acts as if it has encountered a virus. It activates a mechanism that silences any gene with a sequence corresponding to that in the double-stranded RNA.
Scientists quickly learned that they could deactivate virtually any gene by synthesizing a snippet of double-stranded RNA with a matching sequence.
Using GMO Crops to Target a Pest
Scientists at Monsanto are harnessing a new technique called RNAi to try to control the western corn rootworm. Corn the worms feed on is genetically modified to produce a type of RNA that corresponds to an essential gene in the worm. When the worm eats the corn, the RNA kills it by activating a gene-silencing mechanism that is believed to have evolved as a defense against viruses. But some scientists worry that the modified RNA could also possibly affect other insects that eat the corn or become exposed to the RNA in soil or water.Scientists design a type of double-stranded RNA that matches part of an essential gene in the western corn rootworm. Corn is then genetically modified to produce the RNA.When the rootworm ingests the corn, the double-stranded RNA enters its cells. The cells react as if the RNA were a virus and act to defend themselves.
The cell defends itself by “turning off” the targeted gene. This gene, called snf7, is essential for moving proteins around in the rootworm. Turning the gene off causes the worm to die.
The scientists who first unraveled this mechanism won the 2006 Nobel Prize in Physiology or Medicine, and it was initially assumed that most of the use would be in medicine. Imagine drugs that could turn off essential genes in pathogens or tumors, or one that contributes to high cholesterol.
The initial euphoria has cooled somewhat, in part because it has been difficult to deliver the RNA through the bloodstream into the cells in the body where it is needed. Still, the challenges are gradually being overcome, and enthusiasm is rising again.
Using RNAi in insects, at least for beetles, should be easier than in people. Beetles, including the corn rootworm, can simply eat the double-stranded RNA to set off the effect.
One way to get insects to do that is to genetically engineer crops to produce double-stranded RNA corresponding to an essential gene of the pest.
Various genetically engineered crops already harness RNAi to silence genes in the crop itself. These include soybeans with more healthful oil and a nonbrowning apple that appears close to federal approval. The technique has also been used to genetically engineer virus resistance into crops like papaya.
But generally those crops had been developed using methods to modify DNA that were known to work but were not understood at the time to involve RNAi. Monsanto’s new rootworm-killing corn is one of the first in which the crop has been engineered specifically to produce a double-stranded RNA, in this case to inactivate a gene called Snf7 that is essential for moving proteins around in the rootworm. Monsanto, which is based in St. Louis, hopes to have the corn, which it calls SmartStax Pro, on the market late this decade.
The double-stranded RNA could also be incorporated in sprays.
Monsanto is developing a spray that would shore up one of its biggest product lines — crops resistant to its Roundup herbicide. Farmers have grown them widely because they can spray Roundup to kill weeds without hurting the crop.
Roundup, known generically as glyphosate, works by inhibiting the action of a protein plants need to survive. But many weeds have evolved resistance to Roundup. Some of these weeds make so much of the protein that Roundup cannot inhibit it all.
Monsanto’s spray would use RNAi to silence the gene for that protein, reducing production of the protein and restoring the ability of Roundup to kill the weed.
Monsanto is also looking at putting RNA into sugar water fed to honeybees to protect them from the varroa mite. The way to fight the mite now is to spray pesticides that can also harm bees.
“We were trying to kill a little bug on a big bug,” said Jerry Hayes, the head of bee health at Monsanto.
If the RNAi is directed at a genetic sequence unique to the mite, the bees would not be harmed by ingesting it, while the mites would be killed once they attacked the bees. One field trial showed that this technique could help protect bees from a virus. Monsanto acquired Beeologics, a company developing the RNAi technology for bees. It bought at least two other companies pursuing agricultural applications of the technology. And it has paid tens of millions of dollars for patent rights and technology from medical RNAi companies like Alnylam Pharmaceuticals and Tekmira Pharmaceuticals.
But Monsanto is not alone. In 2012, Syngenta signed an agreement to work on RNAi sprays with Devgen, a Belgian biotech company, and later said that it had acquired all of Devgen for around $500 million.
Some scientists are calling for caution, however, In a paper published last year, two entomologists at the Department of Agriculture warned that because genes are common to various organisms, RNAi pesticides might hurt unintended insects.
One laboratory study by scientists at the University of Kentucky and the University of Nebraska, for instance, found that a double-stranded RNA intended to silence a rootworm gene also affected a gene in the ladybug, killing that beneficial insect.
Concerns about possible human health effects were ignited by a 2011 paper by researchers at Nanjing University in China. They reported that snippets of RNA produced naturally by rice could be detected in the blood of people and mice who consumed the rice and could even affect a gene that regulates cholesterol. Such a “cross kingdom” effect would be extraordinary and was met with skepticism. At least three studies subsequently challenged the findings.
In a paper prepared for Tuesday’s meeting, E.P.A. scientists said RNAi presented “unique challenges for ecological risk assessment that have not yet been encountered in assessments for traditional chemical pesticides.”