Science in the Triangle

This spring, U.S. farmers are planting corn fortified with a new genetic weapon against hungry caterpillars: A chemical that an entomologist in North Carolina’s Research Triangle Park found 18 years ago in a batch of spoiled milk from his refrigerator.

The chemical is a protein that works like a natural insecticide. It is made by a bacterium that lives in the soil.

Greg Warren

Bacillus thuringiensis has long been known as a natural pest control. Agricultural chemical giants Monsanto, Dow, Syngenta and BASF have borrowed genetic material from the bacterium to protect crops from insect damage.

But the protein that Greg Warren discovered in the spoiled milk was different from anything that was known or used in agricultural pest control. He tried it on cutworms, caterpillars that chew through the stems of seedlings. It worked.

“They take a bite, they die,” said Warren, a bench-scientist-turned-patent-lawyer at Syngenta’s corporate biotech research hub in RTP.

Genetic engineering, manipulating genetic material in ways that don’t happen naturally, can be as controversial as it is common. Genetic engineering has brought about animals that researchers use to better understand human diseases, animals and plants that produce medicines and agricultural crops that tolerate drought and weed killers, control harmful insects and even produce an extra vitamin.

A year ago, the U.S. Department of Agriculture cleared the genetic trait Warren discovered for commercial use and Syngenta packaged it with other traits in genetically engineered corn seeds that it started selling last fall under the name Viptera.

“It’s a big deal in terms of sustainable pest control,” said Fred Gould, professor of agriculture at N.C. State University. It provides a novel defense against pests that have gotten used to the plants’ old weapons and new pests that moved in once the competition was gone.

Bacillus thuringiensis with spore and crystals

The older bacillus thuringiensis pest control trait, also known as the Cry gene, has been around since 1985 and is in nearly 20 percent of all biotech crops.

The rod-shaped bacterium activates the Cry gene at the end of its life. Just before it dies, it makes a spore to produce offspring and an endotoxin in the shape of diamond crystals to ward off pests.

Strings of bacilli thuringiensis

Earlier in its life cycle, when it divides into what looks like strings of beads, bacillus thuringienses also makes chemicals that act as bioinsecticides. They are called vegetative insecticide proteins or VIPs and are more powerful than endotoxins.

In the early 1990s researchers knew very little about VIPs beyond the fact that they existed, Warren said. “It was an area that hadn’t been explored.”

Warren, who in 1989 had joined Ciba-Geigy’s labs in RTP, wanted to find them. He took dozens of samples, of plants, dust and soil, to isolate bacteria, but none produced a chemical that killed cutworms. His managers at Ciba-Geigy and researchers at universities weren’t very hopeful.

They told him, “You’re crazy, you’re not going to find anything,” Warren recalled.

He didn’t listen. In 1993, he tested a sample of spoiled milk he had brought from home and found a bacillus thuringiensis strain in it. When he cultivated the bacteria and fed the liquid they had thrived in to cutworms, the caterpillars died.

“Out of contaminated food, we found a blockbuster product,” Warren said.

So why did it take 18 years to come to market?

“This is a very unique protein that has very unique properties,” Warren said. “It took time to figure out all those properties.”

Also, it didn’t help that the development of the VIP trait coincided with two large mergers, he said. Again and again, he had to convince superiors to continue funding the research.

In 1996, Ciba Geigy and Sandoz merged to become Novartis. Four years later, Novartis and AstraZeneca merged their agricultural business and formed Syngenta. Warren went to law school to become a patent lawyer the same year the second merger happened. Eric Chen, Warren’s successor as the head of Syngenta’s biostress traits group, oversaw the lab work to make the bacterial VIP gene acceptable to the corn plant.

Last year, Syngenta’s VIP trait won an international award for best novel agricultural biotech product and Michael Mack, the Swiss company’s chief executive, said in an interview with BusinessWeek that Viptera provides Syngenta a chance to challenge Monsanto, the market leader in genetically engineered crop seeds.