Genetic engineering and gene silencing could fight deadly crop mycotoxins—if not blocked by activists

toxin
Maize cob colonized by Aspergillus species, aflatoxin in Senegal. Photo by Joseph Atehnkeng/IITA.

Bt insect-resistant crops, the sibling to the herbicide resistant crops often maligned by anti-GMO activists, have not only reduced insecticide use in the U.S. but also have a food safety benefit: The reduction of mycotoxin contamination of crops, which can harm both humans and animals.

Mycotoxin may not be familiar to most people, but 4.5 billion of us are chronically exposed to it. Produced by the fungus Aspergillus, mycotoxins are compounds that can cause billions of dollars in crop damage, and are known carcinogens. There aren’t many ways to deal with the chemicals once their parent fungi have infested a plant, though developed and developing countries alike try.

Just recently, these mycotoxin events happened:

  • In September, Dutch customs officials halted the import of shelled ground nuts from the United States, because mycotoxin levels above 30 parts per billion (ppb) were discovered in the shipment. An earlier shipment of pistachios from the U.S. was halted in Belgium, after aflatoxin (a type of mycotoxin) was discovered in that shipment.
  • Various European authorities have stopped shipments of spices, nuts, wheat and other foods from Hong Kong, India, Iran, Turkey, Argentina, Italy, and elsewhere, all because of screenings that revealed mycotoxin contamination.

Bt seeds are engineered to express the cry genes from Bacillus thuringiensis. These genes code for an insecticidal toxin which makes the crops resistant to certain pests. Farmers, most especially organic farmers, have been spraying the natural form of the bacterium for almost a century to great effect and with no measurable environmental hazards, as the toxin only interacts with targeted insects but not humans.

“The benefit of Bt corn’s reduction of mycotoxin damage has been virtually ignored in policy debates anywhere in the world,” Felicia Wu, a Michigan State University food and nutrition professor, has noted.

Mycotoxin contamination is expensive, costing the United States alone about $270 million in agricultural losses. The infestation is believed to be worse in developing countries—one study of blood samples showed 90 percent of participants from West Africa and Guangxi, China, were positive for a biomarker indicating aflatoxin. Contamination is also linked to liver cancer, growth impairment in children, and suppressed immune responses.

Two of the most prevalent mycotoxins in agriculture are fumonisins and aflatoxins. Fumonisins are found almost exclusively in corn, while aflatoxins can be found on corn as well as cotton, peanuts, pistachios, almonds and walnuts. Other than the wider use of Bt crops–which are blocked in African countries because of widespread campaigning by anti-GMO ‘environmental’ groups–current methods to curb mycotoxins haven’t been particularly effective. These include (besides border stops), breeding for fungal resistance, practices that impair fungal growth, biocontrol with antifungal strains, and trapping agents.

Now, scientists have turned to a type of non-GMO genetic engineering and found some promising results. If successful, they might also help sidestep the ideological debate over GMOs that has derailed their use in the developing world.

Monica Schmidt, a plant biologist at the University of Arizona, and her colleagues have been testing a type of short strand of RNA (known as “interference RNA” or “RNAi”) for its ability to silence the genes responsible for making mycotoxin.

myco
Testing corn for mycotoxin.

Called HIGS (short for Host Induced Gene Silencing), the technique involves inserting a fragment of DNA that has a sequence expressed only in edible corn kernels. This “DNA cassette” induces the corn to ultimately create small RNA molecules. These RNAs express a sequence similar to an Aspergillus gene responsible for synthesizing aflatoxin. Only when infected with Aspergillus, the small RNA can enter the infectious fungal cell, and matches its RNA sequence with the fungal cell’s RNA that’s making the toxin. When paired, the fungal cell recognizes the double-stranded RNA as foreign and kills it, effectively shutting down the ability to make mycotoxin.

The researchers say that they found no evidence of mycotoxin in corn, in their experiments. But there’s a problem. US and European regulators generally won’t accept any level of mycotoxin above 20 ppb, a very low number that reflects the chemical’s powerful carcinogenic properties. But Schmidt’s experiments had a lower limit of detection of about 93 ppb. While Schmidt showed that the genetic machinery in Aspergillus was shut down thanks to the HIGS RNAi, anybody using this technique commercially will have to show its ability to keep levels below 20 ppb.

Currently, the USDA’s Agricultural Research Service has been testing the HIGS technique in peanuts, with the aim of isolating and quantifying the silencing effects of RNAi in the field.
Still, the technique has shown more promise than other transgenic techniques. Attempts at transgenics (taking DNA or RNA from another species and inserting it into the host organism) have included genetic expression of chloroperoxidase, an enzyme effective at destroying cell walls and degrading Aspergillus and other fungi, and expression of antimicrobial peptides that exist in other plants and could fend off the fungus. More recently, a Spanish study showed that corn crops that were engineered to produce large quantities of carotenoids (including precursors to Vitamin A) also showed reduced levels of fumonisin, a mycotoxin produced by fungus. But the study only found these changes after two or three years of breeding.

Whether RNAi passes regulatory muster is still a question. It is not a transgenic so it does not fall under the byzantine regulatory structure that has stunned so much innovation in genetic engineering. So far, the FDA approved the Arctic Apple, which reduces browning, and a potato that has reduced acrylamide conten,t all thanks to RNAi, a technique that does not involve using genetic material from one species and transferring it to another species.

The technique still has shortcomings, particularly off-target changes that are preventing it from being used to make pharmaceuticals. In the case of the HIGS technology, RNA is expressed only in corn that is infected, and directs only to the invading fungal Aspergillus cell. However, as this recent Genetic Literacy Project story on Schmidt’s work showed, even RNAi work has run afoul of “anti-GMO” sentiment—in her case, from the Gates Foundation, which has in general supported work in genetic engineering.

These genetic techniques are at least showing some effect in the field and the plants themselves, where other more traditional methods have failed. With 4.5 billion people exposed and hundreds of millions of dollars in crop damage every year, there’s a lot at stake.

Andrew Porterfield is a writer and editor, and has worked with numerous academic institutions, companies and non-profits in the life sciences. BIO. Follow him on Twitter @AMPorterfield.

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