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North Carolina’s life-sciences industry is taking a close look at the microbiome, where bacteria and other single-celled creatures facilitate vital tasks, such as fighting disease and absorbing water and nutrients, for animals and plants. By harnessing those powers, crops can be cultivated in harsher conditions, making it easier to feed a hungrier world. Business North Carolina and N.C. Biotechnology Center assembled a panel of experts to discuss where this research stands, how it’s being implemented and what fruit it will bear.
The discussion was moderated by Scott Johnson, vice president of agricultural biotechnology at N.C. Biotechnology Center. The center provided support and hosted the discussion at its Research Triangle Park headquarters. The transcript was edited for brevity and clarity.
What value does the microbiome hold?
EMANUEL: The United Nations estimates the world’s population will be 9.7 billion people by 2050. They will require three times the resources that are currently consumed. Growers and related industries are looking at anything that could make agriculture more dependable, sustainable and productive. We believe the microbiome holds enough potential to warrant serious investments in research, acquisitions and product development. They involve chemistry, biologicals, information technology and much more.
BUGG: Bayer is a life-sciences company, so it is interested in the microbiome for many reasons, including plant and animal health. I’ve been involved with the development of biological products — mainly seed treatments — for 12 years. The research group I oversee at RTP does most of its work in a lab and greenhouse. VOTiVO was my first project with Bayer. It uses a bacteria that prevents small worms — nematodes — from damaging the roots of young plants. It’s applied directly to the seed. It wasn’t the first commercial biological product, but its development and introduction were unique. It opened doors within Bayer and the entire agriculture community. Its mainstream success forced people to look differently at biological products.
BASRA: Biologicals, chemistry, natural and synthetics all work together. We focus on chemistry, but we watch the biological field. We’re a synthetic chemical company, so we created a plant biostimulant. We have partnered with others, such as Bayer CropScience, to launch biostimulant products because their distribution networks are bigger. We are developing a biostimulant that is compatible with Bayer’s fungicide, pesticide or biologicals. Our chemicals make that biological product more efficient or consistent. Biologicals or microbiological products cannot replace chemistry. They can reduce its need or work with it.
BLASIAK: We see short-term opportunities for our biocontrol products, such as a microbe that helps crops fight disease or produce consistent yields despite challenging environmental conditions. Accomplishing that will require understanding how a single organism can affect an entire community. In the long term, if we can understand the interplay among plants, soil chemistry and the microbiome, then we’ll be able to precisely tailor agriculture to each grower’s need. That’s where we’re headed.
SMITH: Biologicals give you the opportunity to utilize modes of action that are in nature. The industry hasn’t emphasized that yet. The chemistry around formulating a chemical ingredient is well understood, and much of that knowledge is maintained as trade secrets. There is a real opportunity to develop technology around formulations that create stable biological products. That would enable their use where infrastructure, such as refrigeration, is lacking. That can be commercialized. It’s hard to do that with only chemistry. Most successful chemistry has a biological model or biomolecule that was discovered and then modified to allow commercial use.
SHAFER: The [Soil Health] Institute’s mission is to sustain and enhance the productivity and vitality of the soil through the advancement of scientific research. It’s a small organization. We don’t wear white coats and work in a lab or greenhouse every day. Instead, we work through partnerships and collaborations with universities, companies and government agencies. Environmental variability is one of the biggest risks that farmers face year to year. Managing soil health reduces variation in crop yield. During a year with normal rainfall, for example, two farmers — one using cover crops that add carbon versus one using conventional practices — will see similar yields. But corn crop yield may be as much as 10% more from fields planted with cover crops during a drought year. If growers’ year-to-year yield is more consistent, that builds confidence in these practices. A better understanding of soil microbiology will allow us to deploy more of these practices, further reducing risk.
How is this research commercialized?
SHAFER: Modern microbiological techniques help us understand how the physical, chemical and biological characteristics of soil function together. Most of the world’s biodiversity is in the soil. There are intimate relationships between microbes and crops. The institute supports research that includes an economic component. You can discover great things, but sustainability requires economic justification. Science can take us a long ways, but then others have to decide how to present it to farmers so they understand its risks, costs and benefits. The institute doesn’t see itself as a policy development shop. We want to be front and center when policymakers want the best available information. We’re feeling our way through intellectual property. I think the model is going to be similar to some public agencies such as Department of Agriculture’s Agricultural Research Service. It’s investing in long-term projects that may include risk but end with some intellectual-property protection so that somebody else can move the findings to market. Nobody wants to commercialize research if it’s always going to be in the open market. The institute’s model is evolving because of how it works as a coordinator with funding organizations. I see it operating more in that mode, so developers retain their intellectual property. We do everything that we can to marry them to people who can commercialize their work, putting it in farmers’ hands.
BASRA: Investments in microbe genetics research have outweighed those for commercializing the findings. Those need financial equality. Only 1% of investments into rhizobial inoculants — which help plants fixate more nitrogen, a limiting nutrient — has gone to making them work better as part of a seed coating. That’s only one example of the gap. There is a lot of exciting innovation happening at the front end.
SMITH: It’s important for commercial entities to focus on securing intellectual property in the short term. Then we’ll work with the patent office and other agencies to define the landscape of individual microbes. The taxonomy of bacteria is poorly understood. Their naming and categorization is based on an out-of-date concept of what differentiates them. Science has surpassed that. The latest knowledge needs to be better disseminated to the patent office and regulatory agencies before we can expect an understanding of how to generate intellectual property and commercial protection around the assets of one type of bacteria.
BUGG: There are many challenges and opportunities. Regulations and how microbes are seen as biocontrol are changing as larger companies and agriculture as a whole moves into this space. Commercialization has to be considered early in the development process, because chemicals will never be completely replaced by biologicals. Everybody kind of shook their head when they came out. They never lived up to their hype, eliminating the need for chemicals in agriculture. That may have held them back in the past. So as we look at combining approaches, it’s important to have biologicals that work within the mold of a chemical-based product. That has to be considered up front, along with the value that a biological product can add to those chemistries. There are many things that can bring value over an untreated seed.
EMANUEL: Treatments can be considered cocktails, combinations of insecticides, fungicides, inoculants and other substances that create coatings. And like those ingredients collaborate, so do companies within the patent environment. Zero-sum games are eliminated by collaboration. How do I or the grower benefit when it’s my patent but you’re going to bring it to market? The patent is an affirmative sense of space. That’s good when we can do that. But a patent doesn’t make growers buy your product. There’s a difference between securing a patent and understanding that you don’t want somebody else excluding you. So sometimes we publish it on websites, putting it in the public domain. Then nobody can claim it and exclude you from that part of the market. They go together.
BLASIAK: Novozymes is a diverse company. It’s always going back to customers to ensure that its products are providing value. However you protect your innovation, you need something that people want to buy. What does the grower want? What value will our product provide? Can we produce it in a way that will provide value to us, too? That’s where we start our research.
How do these developments affect agriculture?
BASRA: Grower involvement is vital. Farmers can be wary of new products. They will use a biological if they are convinced of its potency. We do hundreds of field trials worldwide. Growers bring to the table specific knowledge, such as an understanding of how easy a prospective product should be to apply. We haven’t always incorporated their feedback early in our research-and-development process. That also can be used to shape the delivery portion of the business model. We go through our standard distribution and retailer channels to provide growers with product, which we charge on a per-acre basis. [Charlestown, Mass.-based] Indigo Agriculture is trying a new model. Its debut commercial product was the first microbial designed for cotton plants. It helps them use water more efficiently. So Indigo went to West Texas, where farmers deal with dry conditions. The company asked them to try it. If there is a benefit, then farmers would pay a percentage of the increase it produced.
SMITH: We develop biological pesticides by screening microbes for genetic traits that can be used to modify plant DNA, producing a desired trait. The infrastructure for marketing a genetically modified plant won’t change soon, so we need to partner with Bayer, BASF and other companies in the life-sciences industry to bring those to market. It’s one more way that microbiome research is yielding benefits for the entire industry. Many of the insect-control traits, for example, are under resistance and regulatory pressures. We’re about to launch our first product, which is a biological fungicide. It should be coming to market this spring, pending Environmental Protection Agency registration, which is expected soon. Our commercial director says that the key is how many people buy it the second year. Farmers are innovative, but can you get them to buy the product again?
EMANUEL: The adviser structure is challenged because of many developments happening in a limited amount of time. Our understanding of biologics’ multiple roles of action and how they interact with the other things on the seed or in the soil is progressing quickly. It’s happening because North Carolina is rich in universities and research collaborations. We need to ensure that young people continue to get involved in agriculture, which is the industry’s biggest problem.
BUGG: If you ask a grower to change his normal practices to accommodate a biological product, then the grower needs to see value in that change. And companies need to see the value in changing how business is done. We need biological products that are compatible and stable with the chemicals and production methods used. If you can do that, then you reduce special considerations during application and increase their potential to provide benefit.
Where else will the microbiome take the industry?
BUGG: Bayer approaches the biotechnology industry by acquiring companies and what it can develop internally. It also is interested in licensing and partnering with companies that have technology but not the infrastructure to take it mainstream. We move along those paths simultaneously.
EMANUEL: BASF started Functional Crop Care to harness the power of combining chemistry and biology. Unlocking the potential of soil, seed and crop will enable farmers to keep feeding us three times daily. It needs to be sustainable. Everything growers are facing — variability of technologies, weather and how to use soil as a stable resource — goes hand in hand. That’s where we see commercial potential.
BLASIAK: Novozymes sees the value of innovation around the microbiome for many industries. Animal production is big for North Carolina. We’re examining the microbiome’s role in animal health such as animal probiotics. We’re searching for microbiome opportunities in the household care industry, too. There’s an amazing research community. There are universities, companies and research institutes such as Soil Health, Biotech Center and RTP Foundation. It’s an important network, and our investment in the Triangle — including a $36 million research-and-development lab that opened in 2015 — shows we truly believe that.
BASRA: There isn’t a silver bullet. You have to blend chemistry with soil science. We have to realize the genetic potential locked inside the seeds we have today. Our vision is to become the most successful innovator in crop enhancement. We have access to scientists at [Harpenden, England-based] Rothamsted Research, one of the world’s oldest and foremost agricultural research institutions. That campus is home to a variety of companies. We opened our RTP site last year because of the local ecosystem. Microbiome companies can do seed treatments or soil drenches. Right now, the seed has been the more practical way of adding microbe treatment onto existing chemistry. But you only can add so much to a seed. How we optimize this is critical. Our eyes are open, looking for synergies, whether that’s a seed treatment
or getting a viable commercial product to growers.
SHAFER: Fertilizer recommendations need to be re-examined. Many were developed with genetic varieties and production environments that are no longer widespread. That might address yield-gap issues.
How does this work benefit North Carolina?
SMITH: Biological products can help preserve the diversity of crops that can be grown in a region and help farmers enter new markets. The growing organic tobacco market, for example, is ripe for our new fungicide. Few available pesticides are certified for organic tobacco. So adding a biological fungicide will make it easier to organically cultivate tobacco, which benefits farmers. It sells at a higher price than traditionally cultivated tobacco.
BASRA: It’s critical to address the year-to-year variation in North Carolina agriculture. How do we cut the losses due to climate change, soil imbalances or crop management? Innovative technologies will help. There’s a lot of genetic potential in whatever seeds we have in North Carolina or elsewhere. We are unable to protect and maximize the yield potential of genetics that we have. A lot of emphasis has been put on researching and combating biotic stress, such as pests or pathogens, on crops. Now we are examining abiotic threats such as drought, heat stress and nitrogen levels. Those are becoming a bigger risk. Agricultural chemicals can protect crops from the first, but the others need microbiological solutions. They are complementary technologies.
EMANUEL: Sustainability means two things to BASF. It’s the perpetuity of the business enterprise. First, we invest in North Carolina agriculture because we want it around for many more years. We want reliable and diverse agriculture. North Carolina agriculture involves many crops. Second, we work to meet society’s constantly changing expectations.
SHAFER: The concept of soil health isn’t new, but we are starting to hang numbers on it because of new investigational techniques for its biological component. It probably is the most exciting development I have seen in my career. We are in a position to see this blossom. The institute wants to be where those intersect. That requires partnerships. The institute could have been built anywhere, but it chose North Carolina, one of the best places for fostering such relationships. That creates great opportunities and a great future for the life-sciences industry.