In the woodsy wedge of land between Raleigh, Durham, and Chapel Hill, N.C., new greenhouses, laboratories, and offices are sprouting up. Inside the facilities, scientists are busy working to help farmers improve yields of crops such as corn, soybeans, cotton, canola, and sugarcane. The influx of investment in the area, called Research Triangle Park (RTP), has led local business leaders to call their home turf the Silicon Valley of agricultural research.
Just as the San Francisco Bay Area’s universities and high-tech workforce attracted pioneers of the semiconductor industry and the Internet, RTP has a decades-long history of luring agricultural science firms. What is now Syngenta, for example, arrived there in 1984. Over the years, the region has grown its highly trained agricultural science workforce with graduates from North Carolina State University, Duke University, and the University of North Carolina, Chapel Hill.
The trend has been accelerating. In 2012 Bayer CropScience moved the headquarters of its seeds business from France to RTP. BASF made a similar change, moving its plant sciences base to the area from Germany after becoming frustrated with European resistance to genetically modified crops.
As firms such as Syngenta, Bayer, and BASF increased their focus on agriculture-related research, their ranks of employees in RTP also grew. “The vision and people came first, and now the facilities are catching up,” says Arlene Cotie, a development manager at Bayer.
The region’s new greenhouses and labs will help accelerate work on chemical pesticides, plant traits, biological products, and other technologies that, researchers say, will be needed to help the world double its agricultural output by 2050 and feed an expected population of 9 billion. In the past three years, agbiotech firms have invested about $270 million to enhance their capabilities in RTP, and more expansions are planned.
But even as spending on research grows, so do the challenges scientists need to address. There is an urgent need to help farmers fight the emergence of weeds and insects resistant to pesticides. And to ensure a sustainable food supply, growers need access to technologies that will help crops withstand weather-related stress such as drought and rising temperatures.
Solving these problems requires cross-disciplinary scientific teams, which is why uniting staff in one location is critical, say research executives. “The size of the community generates its own momentum, enthusiasm, interaction, discussion, and scientific exchange,” says C. David Nicholson, head of R&D at Bayer CropScience.
Tours of the new facilities, such as Bayer’s 30,000-sq-ft greenhouse, show how the infrastructure was planned to support the firms’ research strategies. Bayer’s two-year-old glass structure, part of a $78 million investment in RTP, occupies a third floor above the firm’s research labs there.
The greenhouse is subdivided into 21 bays, or separate glassed-in rooms, each with its own air-handling system. Ceiling heights can accommodate tall crops such as full-grown corn. Because Bayer sells products to farmers in many climates around the world, each room gets fine-tuned levels of light, humidity, temperature, and even CO2, all controlled by a centralized computer, explains Seth Levkoff, an R&D specialist at the firm.
Even on a mostly cloudy spring day, the greenhouse is summertime warm and bright. During the daytime, broad-spectrum sunlight passes through textured, low-iron glass, creating a bright, diffuse light that penetrates almost every square foot of space and minimizes shadows. And the day’s length is stretched to 16 hours with high-pressure sodium lights that force robust vegetative growth.
When scientists want to test a new chemical, genetic trait, or biological crop aid, they head to the greenhouse. Take, for example, an experiment to create a genetically modified plant trait. It will result in as many as 100 “events,” or outcomes, that come from inserting genes into different locations in the plant’s genome. Researchers create plant tissue cultures from each event and grow them into young plants.
As the plants grow, samples of their tissue—from the leaves, say, or roots—are taken from the greenhouse and sent to the lab to validate that the desired gene is expressed in the adult plant and to measure the level of expression.
Plants that pass those tests are allowed to grow until their seeds can be harvested by hand. Each plant, and all the seeds from each plant, is labeled and tracked. Only then can seeds be used for trials in outdoor fields.
Plant scientists want to get their new seeds into field trials within two to three years of a trait’s discovery, which translates to a need for large greenhouses that operate year-round. The researchers also grow non-genetically-modified versions of the crops to generate comparison data used to register genetically modified crops around the globe.
Special attention is paid to keeping genetically modified plant material, even down to grains of pollen and dust stuck to seeds, out of the spaces given to non-modified plants.
Controlling variables other than the one being tested is difficult, even in a cutting-edge greenhouse. A visitor notices African marigolds growing in a bay with corn plants. Levkoff explains that Bayer plant scientists use the yellow flowers to attract tiny thrips, a common corn pest, without using a chemical spray. The thrips prefer to feast on the marigold flowers, which can be manually bagged and removed.
Syngenta’s new $72 million advanced crop lab includes a large greenhouse that boasts 30 separate, climate-controlled rooms, some as large as 1,200 sq ft. “In here we can look in the precision chambers, dissect physiological traits, and really understand them,” says Kim White, a research program lead at Syngenta. “We can pick which ones we want to move forward with.”
Sugarcane growing in one compartment thrives under high-light conditions and a climate dialed up to Brazilian.
Around the corner from the sugarcane, tall, green stalks of corn have bags around each tassel and cob. Because corn is an open pollinator, second-generation plants may carry genes from plants other than the parent. So scientists are careful to control pollination and ensure that seeds grown for field trials match up with genes studied in the lab.
Genes that help corn ward off attack from hungry insects are of particular interest to scientists and farmers. Syngenta team leader Hope Hart takes a visitor through the firm’s new lab to describe how those traits are discovered. Sometimes it’s by accident.
Hart was assigned a project to create a single trait to control both western corn rootworm and the European corn borer. The genetic raw material came from two segments of DNA, both borrowed from the soil bacteria Bacillus thuringiensis. Her goal was to modify and combine the segments to code for a new insecticidal protein. She successfully combined genes coding for the two Bt proteins Cry1Ab and Cry3A. But none of the combinations killed the corn borer, and only one was successful against rootworm.
“The effort was a failure—we already had a trait for western corn rootworm,” Hart recalls. “But you never throw anything away that has rootworm activity.” She examined the mode of action of the combination that killed the rootworm and discovered her altered protein was binding to a different gut receptor in the larvae than the existing trait.
This new mode of action will help keep rootworms from evolving resistance to the trait, Hart says. “If an insect loses the ability to bind one protein, it will still be killed by the other protein.”
Corn raised in the greenhouse bore out the result. The root tissue contained the new protein, which, when eaten by the rootworm, becomes soluble in the gut. Gut enzymes then cleave the protein, producing a toxin that creates a hole in the gut and kills the pest. Syngenta began selling the corn trait, called Agrisure Duracade, in 2013.
Farmers also rely on chemical insecticides with different modes of action to control pests and avoid resistance. “We have seen that within a season you can create resistance in the population when using one chemical—a devastating outcome for the farmer and the company,” says Harold Bastiaans, director of advanced biology for insecticides at BASF. When BASF planned its $33 million expansion in RTP, Bastiaans took the opportunity to expand and modernize the insectary, a facility whose sole mission is to raise millions of healthy bugs.
A staff of 70 BASF researchers tests and screens candidate insecticidal compounds that are synthesized in Germany. They try the compounds on insects alone or on plants with pests on them.
Bastiaans says his team is proud of its robust insects. “If we don’t have the insects together with the plants, or if the insects aren’t healthy, the research doesn’t work and we may as well all go home,” he says.
The insectary was designed by William Fisher, global head of insect and plant propagation for BASF. He also manages its day-to-day operations. Fisher and his staff are caretakers for 15 species of insects such as thrips, whiteflies, stinkbugs, and various moths, each in a separate room.
The same insects that are difficult to kill out in the field can be difficult to raise in the lab, according to Fisher. The creatures require optimal temperature and light, along with healthful food and a sanitary environment, in order to thrive in high-density conditions.
“We keep 110 moths inside a 1-gal paper bucket—more than would normally cover an entire acre of cotton. In this unnatural environment, we need them to feed, mate, and lay eggs,” Fisher says. Pest insects can get viral and bacterial diseases and can quickly succumb to parasites.
Not all compounds that kill pests will make it as commercial products, however. A good insecticide candidate must be highly selective, killing only the target pest. “There are many good bugs that we want to keep,” Bastiaans says. “For example, we need to find out very early in the screening process if a chemical will have an impact on bees, and we will screen those out as part of our stewardship program.”
Down the road at Bayer, a new bee care center with a laboratory and 2-acre pollinator garden will help researchers and visitors learn about threats to honeybees. The facility will eventually house up to 10 beehives, says Rebecca Langer-Curry, head of the Bayer bee care program. Bayer sells neonicotinoid insecticides that have come under intense scrutiny for possible negative effects on bee health and behavior.
Bayer scientists will use the lab to test products for their impact on bee health, Langer-Curry explains. In addition, the company is investing in research to protect honeybees from the deadly parasitic varroa mite, which spreads bacterial and viral diseases in colonies.
While some insects are beneficial, the same cannot be said for weeds. The emergence of resistance to the common herbicide glyphosate has inspired firms such as Bayer to take a broader look at technologies that can help farmers.
The combination of glyphosate with seeds genetically engineered to withstand it became the dominant tool to control weeds. But Bayer “never left off on the basic research and development work,” says Cotie, the development manager, who promotes Bayer’s integrated weed management practices. “It has invested in chemicals, seeds and traits, and now biological treatments.” As the effectiveness of glyphosate has declined, research on these other technologies is paying off.
Bayer’s Nicholson says seed treatments are an exciting area for research, in particular for non-genetically-modified, or native, seeds. “Rather than automatically jump to genetically engineered solutions, we can create seeds that have modulated native traits and coat them with biological and chemical treatments that improve yield.” For example, Bayer is testing biological seed treatments that promote the growth of young plants and give them an early competitive edge over weeds.
In 2012, the company acquired AgraQuest and, with it, seed treatment technologies based on microbes. “We’re scratching at the surface of the utility of biologics to farmers,” Nicholson stresses.
BASF made its own big move into seed treatments in 2012 with the acquisition of Becker Underwood. Now the company’s scientists have a special facility for treating seeds, right across the hall from their expanded greenhouse in RTP.
Biologicals are a vital third piece of the crop care puzzle, along with traits and crop protection chemicals, Bastiaans says. “We call it functional crop care.” Microbes and fungi play an important role in the way plants interact with their environment, Bastiaans says, including by helping them optimally use soil nutrients and water.
Growing healthier, more stress-resistant plants from the start may reduce the need for aggressive crop protection later. Syngenta scientists, for example, used a technique called marker-assisted breeding to develop a corn hybrid that can thrive under moderate drought conditions.
During the drought that enveloped the Midwest in 2012, “among the desiccated plants, you could see some that weren’t so dead, or were even a little green, showing the underlying genetic diversity,” Syngenta’s White says. But the genome of successful plants includes multiple genes and pathways geared to surviving drought, making it difficult to map cause and effect.
To develop the hybrid, White worked with a team of quantitative geneticists, plant breeders, field scientists, and molecular biologists to discover DNA markers that correspond to drought-resistant phenotypes. They were then able to screen Syngenta’s corn germplasm library and locate varieties with genes that maintain yield when rain is scarce. Syngenta used traditional plant breeding of those varieties to create the Agrisure Artesian corn hybrid.
Plant scientists have only recently begun to screen plant genomes rather than the plants themselves to find desirable traits, Bayer’s Nicholson says. “We’re moving more and more to generating hypotheses based on an understanding of how genes, alleles, and gene modulations translate to traits in plants.” He believes the tools will become a more prevalent way to understand gene expression in plants.
White is looking forward to expanding Syngenta’s marker approach to new projects with the resources of the firm’s technology center. “This is a fun and important time to be in agriculture,” she says. “We need to grow more food per acre and keep up with a growing population’s shifting diets. I like the idea we are helping to feed people—it’s a great mission.”
Creating An Innovation Ecosystem In Research Triangle Park
North Carolina was not always a global center for research innovation. In the 1950s, the state had the second-lowest per capita income in the U.S., and the economic base of tobacco farming, textiles, and furniture-making was shrinking. Recognizing the need for change, leaders in business, state government, and academia joined in 1959 to create a public-private partnership to attract research business to the region between Chapel Hill, Raleigh, and Durham—the area now known as Research Triangle Park (RTP).
“We needed to do something very dramatic if we were going to have a different future for our people,” recalls Robert T. Geolas, chief executive officer of the Research Triangle Foundation.
The area’s strong collection of universities—including the University of North Carolina, North Carolina State University, and Duke University—was already in place to provide an educated workforce. “We were graduating very smart people from these universities, but they couldn’t find jobs here,” Geolas says. The partners themselves founded the first research company, now called RTI International.
Then, in 1960, the first corporation arrived: Chemstrand, a chemical firm owned by American Viscose and Monsanto. As the computer industry grew, firms such as IBM came to town. By the 1980s and ’90s, the area was attracting pharmaceutical, life sciences, and agricultural firms.
More recently, the European firms Bayer, BASF, and Syngenta have shifted several of their agriculture-related business headquarters to the Triangle. Together they employ more than 2,200 workers. Monsanto and FMC also have agricultural research facilities in the neighborhood, and they will soon be joined by Novozymes, which plans to build a $33 million bioagricultural R&D center.
Research executives at the area’s agriculture firms tell C&EN that having access to local university graduates who are trained in cutting-edge technologies is a major reason they are expanding there. Bayer already employs 50 graduates of NC State.
The relationship between NC State and employers in the Triangle is symbiotic, says Steven A. Lommel, associate dean and director of the school’s Agricultural Research Service. The university provides industry with a pipeline of trained graduates, while company internships and employment opportunities help the school attract top students.
After investing heavily in molecular biologists, RTP companies recently found themselves short-staffed in plant breeding, so NC State created a Ph.D. training center. “We’re responsive in that way,” Lommel says. The school has also created a training program in biostatistics and related analytical methods.
As agricultural research has grown more corporate, NC State’s agriculture school has shifted its own research emphasis. Cotton farmers are now choosing seed varieties developed by major corporations rather than ones bred by publicly funded researchers, Lommel reports. So NC State’s chemists, insect pathologists, and other scientists collaborate with companies to validate the science and efficacy of their seeds and crop protection products.
But the bulk of the school’s research effort is spent working to improve crops and farming methods that are important to North Carolina’s specialized farming base. Scientists work on blueberries, tomatoes, peanuts, and other crops. The Covington variety of sweet potato, used to make french fries, was developed at NC State. And the school is the “last man standing” when it comes to tobacco research, Lommel adds.
Now the RTP community is pulling together again, this time to help inspire more collaboration and networking among workers who rarely cross paths on campus.
“We have a great diversity of small, medium, and large businesses, not-for-profit organizations, start-ups, institutes, and government agencies,” Geolas says, “but bringing people together doesn’t come naturally. If we can create a format for those talents to come together, we’ll have something the rest of the world would envy.”