Outrunning Insect Resistance


By Emily Unglesbee
DTN Staff Reporter

ROCKVILLE, Md. (DTN) -- Researchers have scored a major victory in agriculture's war against insect resistance.

Thanks to a revolutionary new technique developed in a Harvard lab, Monsanto scientists are working to rapidly produce Bt proteins designed specifically to defeat insects that have evolved resistance to the Bt traits in the field.

"This is a groundbreaking tool for us," said Tom Malvar, Monsanto's Insect Control Discovery Lead. "It enables us to stay ahead of the evolution of insect resistance and actively prepare for it."


Bt technology has been widely adopted by farmers to combat insects like the corn earworm and corn rootworm. Planting crops that make their own Bt proteins simplifies insect control and requires less use of chemical insecticides. As of 2015, plants genetically engineered to produce Bt proteins accounted for 81% of the corn acres and 84% of the cotton acres grown in the U.S., according to the USDA.

Insects have now learned to outsmart many of these widely used Bt proteins.

Bt proteins work by binding to certain receptors in an insect's gut. Some insects in a population will inevitably possess an altered gut receptor, to which the Bt protein cannot bind. Instead, the Bt toxin passes harmlessly through their digestive system, and the insect survives. As it mates and its offspring inherit the altered gut receptor, a Bt-resistant population of bugs begins to grow.

When a Bt protein stops working reliably in the field, researchers must find new ones with a different mode of action. This search is laborious and time consuming; scientists must comb through the bacteria that produce Bt and screen any new proteins they find. Industry has introduced fewer than a dozen Bt proteins in the 20 years since the technology first hit the marketplace in 1996.


Enter David Liu, a Harvard chemical biologist with a groundbreaking technique called phage-assisted continuous evolution (PACE). PACE essentially allows scientists to push the fast forward button on evolution. Scientists use the rapid life cycle of a phage (a virus that infects bacteria) to accelerate the protein's evolutionary process, while placing selection pressure on certain desirable traits.

In Liu's most recent study, co-published by Monsanto and Cornell researchers, the scientists used cabbage loopers that had developed resistance to the Bt protein Cry1Ac. The resistant loopers had evolved altered or less abundant gut receptors, which allowed them to dodge the Cry1Ac's binding action.

Liu and his team found a new gut receptor to target in the cabbage loopers. They used PACE to evolve Cry1Ac through 500 complete generations of evolution, under selection pressure to bind tighter and tighter to the new gut receptor. The entire process, which could take about 10 years using traditional protein evolution techniques, was completed in 22 days, Liu said.

In less than a month, the scientists had produced dozens of highly evolved variants of Cry1Ac that bound precisely to the new gut receptor in the cabbage looper. The new Bt proteins proved far more toxic than the old Cry1Ac protein to the resistant cabbage loopers. They were also slightly more potent to non-resistant cabbage loopers than the original Cry1Ac protein, according to Liu.

As exciting as these results are, the study is limited in its scope, noted Bruce Tabashnik, an entomologist and insect resistance specialist from the University of Arizona. "In principle, this exciting new approach could be widely useful," he told DTN. "However, it remains to be determined if the new method will generate Bt toxin variants effective against resistant pests other than the one strain of cabbage looper tested in the study."

Liu is optimistic that the technique will work for other Bt proteins against other insects. "There was nothing about the method we used to evolve Bt proteins or the insect target we chose that wouldn't be applicable to other targets," he told DTN. "We're very excited by how successful this first case was."

Monsanto helped fund Liu's study and has negotiated an exclusive license to Liu's PACE technology. While other companies in other industries may license it from Harvard, no other agricultural company can. Malvar expects PACE will allow Monsanto scientists to craft far more potent and efficient Bt traits. "The most exciting thing about PACE is we think we can target a protein to multiple gut receptors in an insect -- in a sense producing a single Bt protein with multiple modes of action," he said. "In theory, that should reduce the number of Bt genes used in a product."


Although PACE could rapidly accelerate the production of new Bt proteins, getting those new traits into elite hybrids and through the regulatory system will still be a slow march, Malvar noted. The regulatory requirements for PACE proteins will likely be the same as Bt proteins currently on the market, Malvar said. It will be at least a decade before growers see PACE-produced Bt proteins in the field, he predicted.

"This is not about speed to market as much as it is about long-term durability of Bt technology," Malvar said. "This technology allows us to have Bt genes on the shelf and ready to deploy. It's a tool to continually manage insect resistance."

The first PACE-produced products from Monsanto will likely be Bt proteins, but PACE isn't limited to Bt technology. "Anytime a trait involves a protein, PACE can be applied to alter the way that protein performs," Malvar explained. That means PACE could be used to produce new herbicide-tolerant traits or disease resistance traits, among others, he said.


PACE technology has arrived at a critical time for American farmers. Not only are insects evolving resistance to a number of Bt proteins on the market, but a new pest with an aptitude for outsmarting traditional insecticides has recently arrived in the U.S.

The Old World Bollworm, a close cousin of the native corn earworm, was found in Florida in July 2015. The caterpillar is an aggressive pest of 150 plant species, including soybeans, corn, cotton, small grains and a wide variety of horticultural crops. Experts estimate that $843 million worth of U.S. crops could be very vulnerable to the bollworm in the future, given its expected range in the country.

As the bollworm has eaten its way across Australia, India, China, the Middle East, Europe and Brazil, it has evolved resistance to nearly every insecticide used against it, including some Bt proteins.

Bt traits are still the best option American growers have to control future outbreaks of the bollworm, but the proteins are under tremendous pressure in parts of the world such as Brazil and Argentina. Growers there have planted 35 million acres to Monsanto's single-protein Bt soybean product known as Intacta this year.

"As biotechnology and the use of genetically engineered crops expand worldwide and into tropical zones especially, there will be more insect pressure on Bt [traits], and we will experience more and more insect resistance," Malvar added. "So yes, this technology is an extremely timely development."

Emily Unglesbee can be reached at emily.unglesbee@dtn.com

Follow Emily Unglesbee on Twitter @Emily_Unglesbee