Mary Ann Liebert, Inc. | June 2018 | Article Link

INDUSTRIAL BIOTECHNOLOGY: What personal and professional drivers compelled you to start Marrone Bio Innovations in 2006?

PAM MARRONE: After a series of unfortunate events, including 9/11, and a number of events that prevented me from getting the AgraQuest IPO done, I left AgraQuest and needed to continue my work. Some new investors came in and took over the company so I needed to start something new. I felt I hadn’t finished what I needed to do in life and career, and that is: to transform agriculture with effective biological products. So I had to do it again!

So I turned around, left AgraQuest in March, and started April 1st with this company.

IB: There are members of the biotechnology sector that see plant probiotics as part of the next major innovation wave for agricultural biotechnology? Do you share this perspective?

MARRONE: I absolutely do! And everyone else is getting caught up and realizing that there’s potential here. And why? Microorganisms and the natural products they produce when incorporated into pest management and crop production programs, can give better yields and quality than chemical-only programs. There’s a return on investment to the farmer there. And there’s all these other benefits that they have, for example, they don’t leave any residues, they are generally safe to workers so you have more flexible labor management, you don’t have to worry about pest resistance, they can be used in organic farming, and this is what the consumer is striving for.

IB: What are major scientific and technical concepts that make your approach to agricultural probiotics unique?

MARRONE: One of the things we are doing that is different from most others in this space is we have a large natural product chemistry component. Most companies are microbe-only, so they mostly look for live microbes. Our microbes could be live or dead, but we have a chemistry capability that identifies the compounds produced by the microbes and then we optimize that chemistry in the product. That is a unique approach and as a result we’ve been able to develop broader-spectrum and I think higher-performing, better shelf life, easier-to-use types of products.

Using living microbes is great, but living microbes produce compounds so you’re only getting part of the story when you’re looking at microbes alone, not the compounds they produce.

IB: There is a growing interest in developing microbial cocktails for controlling plant pathogens or enhancing the utilization of plant nutrients. What do you see are the challenges to move from pure culture to mixed culture probiotics?

MARRONE: All of our internal products are based on one microbe because that is how the EPA regulates microorganisms—to the strain level. We have been successful finding individual microbes that are effective, broad spectrum and have novel modes of action. We have been a master distributor for Isagro USA, with a product called Bio-Tam 2.0 that is actually two species of Trichoderma. So we have one cocktail in our portfolio. You don’t have to pick one microbe to do everything. It’s really nice to be able to mix multiple microbes and get a broader range of activity and functionality. If it’s for biostimulation, stress-reduction purposes, or nutrient-uptake enhancement, microbial mixtures are great. There’s a lower barrier to entry for registration. It’s much more challenging regulatory process when you’re dealing with the EPA. So when you start mixing multiple microbes for EPA, you have to do toxicology for each individual microbe strain. So with half a million dollars for tox studies, that can be really expensive for a small company. But over time, that level of scrutiny is going to be applied to the biostimulant microbe area as well. It really doesn’t make sense that if you use a microbe for crop protection but you also could use it for plant stimulation, you don’t have to do toxicology and all the rigorous studies that you have to do for crop protection.

IB: What scientific or technological breakthroughs would significantly enhance your innovation efforts?

MARRONE: From our standpoint, formulation is a big deal. We work with a number of microbes that produce compounds that are very biodegradable, and they’re gone so quickly in the environment under sunlight or other conditions. So having better ways to stabilize the microbes and the compounds is key. We like to have all our products be organically listed, and there’s really not that many organic inerts that we can use. There’s a narrow range of compounds we can use to stabilize the microbes and the compounds. Every personal care company and beverage company looking for natural products is looking for the same thing: natural preservatives and other antimicrobials. So that’s a big area—antimicrobials to put in your products that don’t harm your microbes or your natural products in the product but at the same time preserves and keeps out spoilage. So that’s a huge need.

We’re at the very early stages of using microbes for nutrient-uptake enhancement and better efficiency for phosphate and nitrogen uptake. Phosphate and nitrate run-off is really a big problem, particularly in the Great Lakes and Gulf of Mexico. We can solve this by being able to reduce fertilizer input by using microbes. And we have in our collection 18,000 microbes, we know we have sitting in the freezer many microbes that enhance the uptake of phosphorous and nitrogen. And we have some field trials where we were able to reduce the nitrogen and get better control by adding microbes. And that’s just at the very early stages of development. There’s a lot of opportunity for the future here. And we’re not the only ones who see this potential. Bayer just invested $100 million into Gingko Bioworks.

What Gingko is doing is exciting, but we (the industry) haven’t even gotten to the basics of what natural microbes and natural cocktails of microbes can do before you synthetically modify them! With modern genetic and -omics tools, we can better understand the microorganism’s physiology and machinery and as such manipulate it to produce more or different compounds.

IB: What do you attribute to your success in pulling together your innovation team, and how to you maintain a culture of innovation at Marrone Bio Innovations?

MARRONE: We’ve been able to get seven products from six new active ingredients to the market in eleven years; I don’t know that anyone else has achieved that level of productivity. These are six EPA-registered products, which is pretty remarkable. I do think it has to do with the way we do R&D. I have an excellent head of R&D—Dr. Amit Vasavada. He is a very good leader.

But it is also about developing functional teams working together. Teams with different expertise—natural product chemistry, analytical chemistry, plant pathology, entomology, fermentation, formulation—all working together very closely and in parallel in project teams. The interaction between the biologists and the chemists is key and so is having parallel work instead of sequential. A lot of work in industry is staged-gate development, where you work in sequence. And that historically has been in the agchem industry because of the high cost of developing a chemical. On average, it takes 12 years and $300 million. Whereas with biologicals, it’s a few million, and a few years to get a product to market. You don’t have to do this sequential, staged-gate process, you can work on fully describing the efficacy while also working on the natural product chemistry and optimizing the microbes. All of the functions can be working at the same time. I think that’s a big reason for our success.

Also where we sourced and how we isolated our microbes was very different than what I’ve done before. We’ve tried a lot of new things. Many companies isolate from soil samples that have been sitting around a long time, and what happens is a lot of cool microbes die off and then you end up with your sporiforms, your Bacillus, and your actinomyces. By processing our samples differently, we were able to get a lot more biological diversity and discover many new species. So we have thousands of novel strains and we discovered several new species of microbes that produce novel compounds as well.

IB: What are the marketing and economic challenges that you encounter in convincing farmers to trust and rely on your probiotics?

MARRONE: We’ve been doing a lot of surveys of late. We hired a company that does farmer peer-to-peer marketing for us to find out the answer to this question. We’re a public company, we want to grow faster. And what we’re finding is our biggest challenge is simply lack of awareness. Number two, is education and understanding of the category. Not even our products, just our category. It’s increasing through the Bioproducts Industry Alliance, a trade group I founded in 2000 and used to be called the Biopesticide Industry Alliance. We’ve been doing a lot of education on this category. But it is remarkable how most growers don’t really know about biologicals at all.

The technology is becoming mainstream. We’re at a tipping point, but it really is awareness and education. And then the education needs to be on understanding that these are different modes of action than chemicals. They work differently, you have to understand their modes of action and how to deploy them properly. It is not “do they work” but “how to make them work.” And how to use them in integrated programs. Once you do, you get really good results—higher yields and quality—a higher ROI for the grower.

We also have a big barrier in the land grant university system. The land grant extension system is very traditional in how they evaluate products. Most of them also have a very low understanding about biologicals, how they work, and how to deploy them. They are still very reductionist, in that it has to be one microbe, one biopesticide or biostimulant against a full cocktail of chemical solutions. Really that’s not how to do it. They’re integrated, whether it’s a microbe stacked with a chemical on a seed or foliar applications of microbes in combinations (tank mixtures and rotational sprays). Yes, you want to know what your product does alone, but that’s usually where it stops and they don’t go the next step to test the integrated approach, like farmers use them.

IB: What regulatory issues do you see impending the deployment of plant probiotics?

MARRONE: Right now there are still a lot of snake oils particularly on the biostimulants side. I would say that the biostimulant and microbial probiotics area are where biopesticides were 15–20 years ago. When I started there was a snake oil image of the biopesticides category, and we needed to spruce up its image and basically create standards of quality of the products that the customers would perceive are not snake oil. Biopesticide products have gotten better, with more science behind them, including better formulations and manufacturing processes. For biostimulants there are lower barriers to entry in terms of regulation to get a probiotic or biostimulant to market versus a biopesticide that is tightly regulated by the EPA. So there are a lot of companies in biostimulants, a lot of mom and pops, bathtub brews and cocktails of microbes.

This is changing now. There is a Biostimulant Coalition that is developing a better regulatory and quality framework for the probiotics and biostimulants category, like we did for biopesticides years ago. You’ll see a change in that. I know that our head of regulatory is part of that coalition, went to Washington, and met with USDA to ask if they would be the agency for the development of that regulatory framework. Indeed, that is included in the draft Farm Bill.

IB: How would describe to young people the opportunities available to them in this exciting field of agricultural biotechnology?

MARRONE: This is the most exciting time to be in this field. You don’t have to follow the traditional career paths, which would be either you come out of school and you become a professor or you go work for a chemical company or the government (USDA). Now, there are so many companies and start ups. I had a graduate student from the University of Wisconsin call me and say, “I have this platform that is part of my Ph.D. thesis for rapid diagnosis of plant pathogens and I was wondering, should I think about forming a company around this?” That’s unheard of, that a young person right out of school would be thinking about creating a company. But that’s where we’re at right now! There’s so many young people starting companies. And there’s so many women and minorities starting companies as well. So it’s a really exciting time. There’s a lot of jobs, and a lot of big problems still to solve.

There’s such a sense of beginning of understanding the microbiome and the products they produce and what they do. We went from the synthetic chemical era with agrochemicals and fertilizers, leapt over the natural products arena, and went to GMO crops. In pharmaceuticals, you had this huge natural products era and over 50% of drugs come from natural sources, whereas it’s only about 15% in agriculture. We still have this whole era of natural products in biology that we have missed. That creates a very exciting time.

IB: How can we at IB help you drive innovation in this very important area of agricultural biotechnology?

MARRONE: There’s a lot of hype about a few companies. They make the circuit and they get the awards. And they’re backed by very high-profile investors. I mean, that’s the business model, it’s like Silicon Valley, right? And that will get valuations up. But there’s a lot of other companies to cover. I think it’s important to not just follow the herd and really seek out all the different startups.

Surprisingly, Marrone Bio Innovations struggles to get some of that ink. We put out a lot of press releases but we struggle because we’re old news. We’re not a hot startup anymore. And we’re not about the hottest genomics and sexiest technology! But we’re like, wait a minute, we have seven products on the market as a basis for growth! So it’s about wading through that hype and broadening the coverage.