When disease decimated Ireland’s potatoes in 1845, farmers were at a loss to explain what caused their staple crop to rot in the fields. The blight continued in successive growing seasons and by 1851, more than one million deaths were attributed to what came to be known as the “Great Famine.”
Fungicides can now prevent infestations of Phytophtora infestans, also called late blight, the pathogen at the root of Ireland’s potato famine. But that fungus-like microorganism and others still threaten plants today, putting hundreds of millions of dollars worth of crops at risk each year. Bayer’s efforts to add to its portfolio of 17 fungicides has led it to Trana Discovery, a Cary, NC-based biotech startup working to discover new crop treatments by targeting a cellular process fungi need to reproduce.
Bayer and Trana recently announced a research partnership intended to discover and develop new fungicides. The companies aren’t disclosing any financial terms of the deal, nor are they saying which fungal diseases or crops they are targeting. But Mark Turner, alliance manager for Bayer’s Alliance Management Department, says the Trana technology offers the potential for discovering new fungicides that are more effective, and also have fewer harmful effects on the environment.
Fungicides work by damaging cell membranes, blocking key enzymes or proteins, or interfering with important metabolic processes. Trana’s search for potential fungicides focuses on transfer RNA, or tRNA, a molecule that plays a key role in how cells in all organisms make essential proteins, says Trana CEO Steve Peterson. Trana has developed a way to screen chemicals to find the ones that show promise in blocking tRNA. Preventing fungi from using tRNA to make essential proteins leads the cells to destroy themselves with their own enzymes.
“It basically is a suicide switch for the microorganism,” says Peterson, a pharmaceutical industry veteran who has held various product development and marketing roles at companies including Eli Lilly (NYSE: LLY) and GlaxoSmithKline (NYSE: GSK).
Though Bayer CropScience is headquartered in Research Triangle Park, NC, not far from Trana’s offices, the German company’s fungicide research operations are located in Lyon, France. Trana’s initial work will involve running fungi genomes through a database in order to identify tRNA that hold the most potential as targets for a new fungicide, Peterson says. After identifying promising targets, Trana will screen thousands of chemicals to find the ones that naturally inhibit those tRNA molecules.
Trana’s approach is more targeted than the historical way of testing a library of chemistries on crops and seeing what effect they have on both the plant and the fungus, says Paul Ulanch, executive director of the biotechnology commercialization center at the North Carolina Biotechnology Center. Ulanch knows of no other companies developing new fungicides by targeting tRNA. (The Biotech Center, whose support of North Carolina-based biotech startups includes providing loans and grants, has loaned a total of $310,000 to Trana.)
One reason that crop protection companies are looking for new fungicides is concern about resistance to crop chemicals now in use. The most common way that fungi develop resistance is through mutations that alter the part of a cell targeted by a fungicide, which makes the microorganism less sensitive to the chemical, according to the Fungicide Resistance Action Committee, a part of the Belgium-based agricultural technologies trade organization CropLife International. While a fungicide may kill the initial population of pathogens, mutant fungi that aren’t sensitive to the chemical may be unaffected. These changes can happen quickly. FRAC notes that a single Phytophthora infestans lesion on a potato plant leaf can produce thousands of spores, each of them capable of becoming a new lesion within days.
Besides addressing fungicide resistance, the Bayer-Trana partnership might also be able fill in gaps in crop protection left by products that don’t work on certain fungal diseases, Ulanch says. He adds that there is now greater need for narrower, more targeted fungicides given the growing adoption of agricultural microbials, applications of beneficial microorganisms that promote plant health or help crops resist environmental stresses, such as drought. A recently launched microbial product from Monsanto (NYSE: MON) and Novozymes (NASDAQ OMX: NZYM), for example, which was developed to help improve corn yield, is based on a fungus found in soil.
Turner says that any new fungicides that emerge from Bayer’s partnership with Trana will be tested to avoid “off-target effects” on plants or beneficial microbes. Bayer will finance Trana’s research under the partnership, and will own any candidates that emerge from the research. The German company will also be responsible for bringing these chemicals through testing and regulatory approval. The partnership is not exclusive, which leaves Trana free to pursue collaborations with other companies.
The Trana technology, originally developed at North Carolina State University, has applications in both plant and human health. When the company spun out of the university in 2005, its initial work focused on developing antibiotic and antiviral drugs. The company still has those programs but has since turned its focus to plants. Trana’s research now includes programs addressing fungal diseases that affect bananas, oranges, and wheat.
Bayer and Trana haven’t discussed broadening the research collaboration to find anti-infective drugs for human health, Turner says. But Bayer might be interested in finding more agricultural applications of Trana’s technology.
“If the technology works well, it would be natural to consider it for pesticide discovery,” Turner says.