The search for less-toxic agents for disease control in crops has led many researchers to take up investigations into more natural solutions. By the end of the twenty-teens, the hot topic in plant protection was preparations of beneficial microbes. Certain species of bacteria and fungi with names like Bacillus and Trichoderma were marketed for organic growers to spray on their plants for protection, and ongoing research tempted with ever more efficacious products.
In 2019, Pam Marrone addressed the annual EcoFarm conference, the premiere gathering of organic growers in the western US. Pam had achieved rock star status through nationwide press coverage. Her secret sauce was the highly efficient methods of bioprospecting and screening microbes and plants for beneficial activity around which she founded her company, Marrone Bio Innovations. Her efforts had brought several effective natural products onto the market, such as Regalia, the recommended product for protecting cannabis from powdery mildew. The theme of her presentation at the conference was not tips for farmers on how best to use beneficial microbes on their farm, or how many farmers her company had helped, but rather how much better her business model was compared to the mature agrochemical companies. While the Monsantos and the Pioneer Hi-Breds were consolidating to boost profits, Marrone was still growing.
Meanwhile, a young Latina organic farmer attending the conference had expressed privately how expensive commercially produced natural products were. With commercial products out of reach, she had turned to Spanish-language videos online offering do-it-yourself methods of finding and raising one’s own beneficial microbes. She had created a home brew that seemed to give her good results, but it was not the kind of overwhelming effect that gave her confidence that it would still work in the future.
Later in 2019 there was a breakthrough in the area of bioprospecting. California Governor Gavin Newsom signed a law opening state parks, which had theretofore been off limits to profit-making activities, to the commercialization of research materials found there. The spur for this legislative effort was the discovery by the lab of researcher Johan Leveau of a microbe that could help in the fight against Fusarium. This is a genus of fungus that lives in the soil and infects the roots of plants, which can lead to wilting and death. Conventional growers keep Fusarium at bay with fumigation and fungicides, but organic growers must rely on preventive methods such as genetic resistance and crop rotation to keep their crops healthy. Each of these methods has its limitations. The fungus is continuously evolving, threatening to render the currently resistant crop varieties susceptible. And Fusarium is notoriously adept at surviving in high-organic-matter soil, the kind of soil that organic growers actively try to build, greatly hampering the effectiveness of crop rotation for combating this group of pathogens.
The Leveau lab stumbled upon the microbe in question from a survey of bacteria in northern California’s Jug Handle State Park to figure out the connection between environmental factors and the composition of the soil microbiome. Factors such as acidity and organic matter are thought to be responsible for the types of bacteria species present in a soil sample, but it’s hard to tease apart what the of effect of these factors is versus the effect of the complex mineral composition that the soil gets from the parent rock it originally came from. What sets the soils of this state park apart is a process that gives different areas of soil different pH and organic matter while keeping the mineral makeup the same.
The Mendocino Steps formation was created from a series of uplift events that happened at intervals of about 100,000 years. While the area has all the same parent material, as you go inland and up in elevation, the soils are older and more weathered, an array known as a chronosequence, where the soil in the lowland is presumed to be just like what the soil in the uplands had been 100 or 200 thousand years ago. The cool rainy climate of California’s north coast created soils that became sandier, more acidic, and lower in organic matter over the millennia. The Leveau lab showed that these factors did indeed have an effect on the bacterial species present, but of special interest to Dr. Leveau was the possibility of finding members of a recently described bacterial genus, Collimonas.
Professor Leveau was part of the team that first described this group of bacteria. They had taken samples in the dunes of the Netherlands and found a species so unique that it had to be classified in its own genus. It was adapted to life in a nutrient-poor environment by its ability to mobilize nutrients from insoluble forms and its ability to feed on fungi. In California the Leveau lab used special culture techniques involving insoluble nutrients to make sure they could pick out these rare bacteria from the soup of microbial life in their samples.
Where regular culture methods failed, and even high-sensitivity methods like qPCR could not discern, the special techniques yielded a dozen instances where a single bacterium grew into a visible colony that turned out to be Collimonas. These colonies, referred to as isolates, included all three species of Collimonas known at the time. The expanding number of isolates being discovered around the world presented the opportunity to explore an intriguing question: If Collimonas bacteria can feed on fungi, might they be useful in fighting fungal pathogens of crop plants?
The Leveau lab set up a screening of the three Collimonas species, represented mostly by the isolates from Netherlands and California, against a range of fungi and fungus-like organisms, mostly plant pathogens. They would put a Collimonas isolate in a Petri dish with a target organism and watch the two battle it out. Whether the target ever attacked the bacteria is not reported, but sometimes the bacteria were not as successful in vanquishing the target. After pairwise matches of every isolate against every target, the researchers had found a winner, the isolate code-named Cal35. This isolate advanced to the next round, battling the particular foe Fusarium o.f.sp.l., a pathogen of tomatoes, but this time in pots in a greenhouse.
Cal35 had defeated this Fusarium handily on a plate, but many a biocontrol organism has shown promise in the lab, only to fail in a real-world situation. Even commercially available biocontrol products like the Bacillus preparation known as Serenade Soil are expected to only give partial control, and only in a subset of circumstances. To improve the odds, the Leveau folks tested Cal35 not just by itself, but also in combination with Serenade Soil.
The goal in the greenhouse round was for the biocontrol agent to either reduce the discoloration in the stem that the pathogen causes as it grows up from the roots or to allow more growth of the plant in spite of the infection. Cal35 by itself was not up to the task, but then neither was Serenade Soil. Only in combination could the two bacteria take down the pathogen by a significant degree. The duo reduced the discoloration in all five trials and increased the top growth in four of the trials. It was time for the final round, the field.
In the field round, the criteria were reduction of stem discoloration, plant growth, marketable fruit yield, amount of sunburned fruit, and amount of green fruit. Once again, Collimonas Cal35 and Bacillus Serenade Soil individually were no better than no treatment at all, but in combination the two reduced discoloration in both trials. In the scoring of plant growth, it looked like the combined treatment was ahead in the first trial, but it was not ahead by enough for a conclusive win (in scientific terms, not significantly different). For the second trial, the researchers doubled the number of infected plants to firm up the trend they were seeing, and in that trial the combination treatment conclusively increased growth. And while it did not increase yield or decrease green fruit, it decreased the amount of sunburning.
With a new non-chemical treatment proven effective against Fusarium in tomato, the expectations of Professor Leveau’s profession made the next step obvious – take out a patent on the combination therapy, dubbed Collinade. Big growers would surely go for a commercial product that would give them additional non-sunburned tomatoes to tempt organic produce consumers. The only obstacle was Section 5001.65 of the California Public Resources Code, the law outlawing the profiting from resources obtained in state parks. With the lure of less-toxic disease control, Leveau was able to successfully make the case before the legislature for a carveout allowing commercialization of organisms collected for scientific research, with just a few strings attached. One can wonder whether the Professor was thinking of the royalties that would accrue once the product was commercialized, or whether he was acting out of the belief that the promise of profits accruing to a private company would make the best channel for rolling out his remedy.
It is certainly the usual scenario that breakthrough discoveries arising from government-funded research at universities and independent labs get transferred to private companies that can scale them up quickly and collect all the profits. Think Moderna and mRNA vaccine technology. A Harvard postdoc, Luigi Warren, using funds that included a significant portion from the National Institutes of Health, figured out how to reprogram cells into stem cells by inserting mRNA codes into them. His professor, Derrick Rossi, anxious to fulfill the promise of stem cell therapy to cure an array of maladies, decided to form a startup company to market products. He consulted some colleagues at Harvard and MIT who had experience creating startups plus a lot of royalty money in their bank accounts, and he and his colleagues formed ModeRNA. The guys with the money had started out as researchers who made groundbreaking contributions to healthcare, but with their string of startups they had grown accustomed to doing well by doing good. They immediately pivoted to applications that would turn cells into factories for proteins like vaccines. The CEO they chose was so profit-driven that Professor Rossi dropped out of the team, although he did maintain a financial interest in the company.
The team of science entrepreneurs proved itself adept at attracting investment money, including $25 million from the government agency DARPA to develop a technology for a vaccine that would protect the country from a hypothetical pandemic. When the pandemic materialized, the government paid Moderna nearly a billion dollars to scale up production, with a promise to purchase 300 million vaccine doses for nearly $5 billion. The guys with the money had struck gold like never before.
Somewhere along the line, though, the desire to do well eclipsed the desire to do good. Moderna used a technique for generating a more stable spike protein for robust antibody production that had been developed earlier by researchers at Dartmouth, Scripps Research, and the NIH who were working on the MERS virus, and Moderna never bothered to compensate those earlier researchers until they brought suit. Even worse, Moderna refused to license its technology package to factories in countries of the Global South that could extend the vaccine to the populations of the entire world, instead keeping their technology secret. In spite of warnings that leaving billions of people unvaccinated was sure to create vaccine-eluding mutants, and in spite of leverage that the US Government should have had due to its crucial funding of the development of the technology, Moderna would not be bound by pleas to do the right thing.
A South African lab was finally able to reverse-engineer the mRNA vaccine against Covid, but the extra eight months required to come out with the homegrown version meant hundreds of thousands of lives lost. And just as predicted, the feared mutant arose in the Global South. When the news broke, Moderna’s stock soared, and the CEO got $800 million richer in a week. Let that sink in a moment: Moderna held onto its secrets until a mutant strain appeared, the financial markets looked to them to save the world again, and they raked in billions as a result of their secrecy. Could the profit-driven CEO and the guys with the money have come up with a business plan that ruthless?
Which is not to say that Professor Leveau would ever commit patent infringement or rake in millions based on his discovery. Rather, the pattern of companies profiting from public investments is well established; it’s the milieu in which university researchers operate. Professor Rossi, in spite of his disillusion with Moderna, went on to found additional startups. It’s as if these academics see no alternative for disseminating laboratory discoveries to serve the public, never questioning the nature of the system, like the fish that never notices that it is bound by water.
Are there alternatives? There’s the example of Jonas Salk, who, upon developing the polio vaccine, placed its patent in the public domain. There followed a massive vaccination campaign without the need for wealthy shareholders to make a killing. In the area of agriculture, there is the example of velvetbean.
Native to South Asia, velvetbean was trialed by Nestlé in Central America as a coffee substitute. The peasants there were astounded by its ability to outcompete weeds and the copious amount of organic matter it left at the end of the season. When they tried it in their rotation, it quickly restored fertility to the soils that had been depleted by Green Revolution agrochemicals and the erosion from the hillside soils where the peasants were forced to farm after export agriculture dominated the flatlands. Velvetbean seeds were passed among neighbors, then from refugees fleeing the Guatemalan civil war to Mexican peasants. The peasants’ network Campesino a Campesino was formed, and the seeds traveled from Mexico onward to the organized peasant society under the Sandinistas in Nicaragua, and onward still to Cuban farmers who were turning to agroecological methods after the collapse of the country’s socialist-bloc trading partners. Hundreds of thousands of peasants were reached with no need for profit-hungry corporations guarding patented methods. There were international non-governmental organizations and some sympathetic government agencies involved, but this miracle crop profited only the people who used it.
Could a network of farmers’ associations, extension services, university labs, non-profits, and governmental agriculture departments distribute the makings of a proven microbial preparation to the farmers who need it? It’s conceivable. Consider plant protection practices that can’t be patented, such as improved pruning methods or delayed planting. Such innovations are incompatible with the profit-driven system of intellectual property protections, where the outcome is supposed to be a commercial product like Regalia for powdery mildew. They can only catch on through extension plus farmer buy-in. Indeed, some widespread non-patentable agricultural practices – think organic farming or no-till – have caught on without depending on the profit motive to disseminate them. Without the need to make a profit, non-patented agricultural innovations are within reach of those plucky farmers who put in the hard work to feed the community while stretching their scarce funds. And farmers are a resourceful bunch – alternative agriculture researchers who work directly with farmers often depend on the farmers themselves to come up with the innovations for the researchers to investigate. So perhaps farmers and researchers could collaborate to formulate methods for deploying biological disease suppression agents.
If that sounds like a longshot to you, to mainstream agriculture researchers it sounds like a fairy tale. The history of the Campesino a Campesino movement is one of clashing with the existing rural development and agriculture research establishment. So the question may not be whether Professor Leveau was motivated by the profit motive to seek a patent on Collinade. To be fair, the bill he successfully advocated guaranteed a generous portion of the profits for the benefit of the state park system. The professor may have merely been following the only pathway he could conceive. The legislature may have breached the wall separating profit-making activities from the public sphere because they are in a matrix where they see no alternative. None of these folks seem to have heard the lament of the Latina farmer for whom the breakthrough biological products are out of reach, and certainly not to have prioritized her and the other farmers in her position. Perhaps the question should be how we can get past the façade where private profits are presented as the only way to promote the public good and instead see the skewed foundation of assumptions upon which the intellectual property regime is based.
And then there is the question of whether significant profit can be wrung out of the agricultural sector at all. While Pam Marrone was touting her business model of biological innovations for plant protection at the EcoFarm Conference, her company was deeply in debt, and although her sales were growing every year, they never reached the break-even point. Eventually this bio-based company had to be consolidated, with Dr. Marrone selling the rights to her product line to an Argentina-based company. In the agricultural sector, which contends with margins as thin as a biofilm, one that is populated by behemoth conglomerates at one end and dreamers working 80-hour weeks while barely scraping by at the other, a sector that is kept afloat by generous bipartisan government support, those seeking to make a fortune need to check their expectations. It kinda makes the idea of sharing innovations through a horizontal network of farmer organizations supported by governments and non-profits sound like a sensible idea.