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Beekeepers are desperately battling colony collapse disorder, a complex condition that has been killing bees in large swaths and could ultimately have a massive effect on people, since honeybees pollinate a significant portion of the food that humans consume.

A new weapon in that fight could be RNA molecules that kill a troublesome parasite by disrupting the way its genes are expressed. Monsanto and others are developing the molecules as a means to kill the parasite, a mite that feeds on honeybees.

The killer molecule, if it proves to be efficient and passes regulatory hurdles, would offer welcome respite. Bee colonies have been dying in alarming numbers for several years, and many factors are contributing to this decline. But while beekeepers struggle with malnutrition, pesticides, viruses, and other issues in their bee stocks, one problem that seems to be universal is the Varroa mite, an arachnid that feeds on the blood of developing bee larvae.

“Hives can survive the onslaught of a lot of these insults, but with Varroa, they can’t last,” says Alan Bowman, a University of Aberdeen molecular biologist in Scotland, who is studying gene silencing as a means to control the pest. 

The Varroa mite debilitates colonies by hampering the growth of young bees and increasing the lethality of the viruses that it spreads. “Bees can quite happily survive with these viruses, but now, in the presence of Varroa, these viruses become lethal,” says Bowman. Once a hive is infested with Varroa, it will die within two to four years unless a beekeeper takes active steps to control it, he says.  

One of the weapons beekeepers can use is a pesticide that kills mites, but “there’s always the concern that mites will become resistant to the very few mitocides that are available,” says Tom Rinderer, who leads research on honeybee genetics at the U.S. Department of Agriculture Research Service in Baton Rouge, Louisiana. And new pesticides to kill mites are not easy to come by, in part because mites and bees are found in neighboring branches of the animal tree. “Pesticides are really difficult for chemical companies to develop because of the relatively close relationship between the Varroa and the bee,” says Bowman.

RNA interference could be a more targeted and effective way to combat the mites. It is a natural process in plants and animals that normally defends against viruses and potentially dangerous bits of DNA that move within genomes. Based upon their nucleotide sequence, interfering RNAs signal the destruction of the specific gene products, thus providing a species-specific self-destruct signal. In recent years, biologists have begun to explore this process as a possible means to turn off unwanted genes in humans (see “Gene-Silencing Technique Targets Scarring”) and to control pests in agricultural plants (see “Crops that Shut Down Pests’ Genes”).  Using the technology to control pests in agricultural animals would be a new application.

In 2011 Monsanto, the maker of herbicides and genetically engineered seeds, bought an Israeli company called Beeologics, which had developed an RNA interference technology that can be fed to bees through sugar water. The idea is that when a nurse bee spits this sugar water into each cell of a honeycomb where a queen bee has laid an egg, the resulting larvae will consume the RNA interference treatment. With the right sequence in the interfering RNA, the treatment will be harmless to the larvae, but when a mite feeds on it, the pest will ingest its own self-destruct signal.

The RNA interference technology would not be carried from generation to generation. “It’s a transient effect; it’s not a genetically modified organism,” says Bowman.

Monsanto says it has identified a few self-destruct triggers to explore by looking at genes that are fundamental to the biology of the mite. “Something in reproduction or egg laying or even just basic housekeeping genes can be a good target provided they have enough difference from the honeybee sequence,” says Greg Heck, a researcher at Monsanto.

The beauty of RNA interference, says Bowman, is its specificity—the nucleotides in the double-stranded RNA treatment must exactly match a portion of the gene product that it targets for the silencing to work. Researchers have sequenced the whole genome of the honeybee and portions of the mite genome, so the task of finding ideal targets should not be difficult, says Heck.

Other companies are also looking into RNA interference as a way to protect bees from mites. Honeybee health company Vita, based outside London, recently partnered with Bowman’s home institution the University of Aberdeen and the U.K.’s National Bee Unit to develop their own gene-silencing technology.

Bee experts see promise in the method. “It hasn’t had a great success yet, but the proof of concept is there,” says Rinderer, whose USDA research group is taking a classic genetic approach to fighting Varroa: his group develops and maintains stocks of bees that are more resistant to the pests, some because they are simply better at cleaning out larval cells infected with the mite.

The specificity and precision of topical RNA interference could be used for other agricultural tricks, including perhaps making weeds once again sensitive to a Monsanto herbicide that they have developed resistance to, says Heck.

The main challenge going forward is the uncertainty of how regulators will respond to the gene-silencing technique. “Anyone wanting to use double-stranded RNAs is waiting to see what the regulators are going to allow,” says Bowman. “There is no precedent for it.”

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Credit: Monsanto

Tagged: Biomedicine, RNA, Monsanto

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