Will microbes save agriculture?

Right under our feet.

That’s where David Perry believes the next agricultural revolution will come from – the millions of unseen microbes in soil that play a crucial but complicated role in the well-being of plants.

Perry believes that he can repackage beneficial bacteria and fungi as something akin to human probiotics and deliver them to plants to alter their microbiome in ways that will boost growth, increase resistance to drought, disease and pests, and reduce farmers’ reliance on fertilizers and pesticides.

Like Perry’s Cambridge, Mass.-based Indigo, a slew of other start-ups and all of the top international agro-industrial companies – BASF, Monsanto, Bayer CropScience, Syngenta, Arysta LifeScience -- are rushing into a market that analysts believe could more than double in value, to $4.5 billion, by 2019.

That shift has created a buyout market for California start-ups.

BayerCropScience paid $425 million for AgraQuest of Davis, Calif., in 2012, largely for its enormous collection of bacterial strains. In 2013, Monsanto acquired key assets of Agradis and Synthetic Genomics, two related La Jolla-based companies that own large microbial libraries as well as patented genome analysis techniques. Terms of the sale were not disclosed.

DuPont bought Taxon Biosciences Inc. of Tiburon, Calif., for an undisclosed amount last year.

Big Bio and Big Ag aren’t more than a degree removed from Indigo, either. Astrazeneca, Nestle Health Sciences and Bayer CropScience formed a strategic partnership last May with Flagship Ventures, the MIT-rooted fund whose in-house incubator, VentureLabs, birthed Indigo as Symbiota in 2014 and reflagged it as Indigo in February.

Indigo will offer two commercial products this year, said Perry, who came aboard as chief executive last year. The company’s laboratory and field tests of a microbe-based seed coating showed a 10% increase in yield for several crops, including corn, soy, wheat, cotton, sorghum, canola, chickpeas, tomatoes and strawberries, Perry said.

“If we do that well, we make healthier plants, and healthier plants have a greater yield and need fewer chemicals and fertilizers and water to produce that yield,” said Perry, a serial entrepreneur who previously launched several companies in California (including one that suffered a spectacular implosion during the dot-com bust).

University of Arizona microbiologist Betsy Arnold was wooed to work on Indigo’s science team by MIT bioengineer and inventor Geoffrey Von Maltzahn, a principal in Flagship Venture Labs.

Fresh out of Duke University with an undergraduate degree in biology, Arnold was collecting leaf samples at the Smithsonian’s Barro Colorado nature preserve in Panama to see what was eating them and what was causing disease.

In a petri dish held up to the light, the leaves looked like a stained-glass window. Arnold thought maybe she was just a sloppy microbiologist, but soon realized that she had stumbled into leaves packed with biological hitchhikers, or endophytes, colonizing leaf tissues.

“It blew my little mind,” said Arnold, who soon changed her focus. She now runs a microbiology lab at the university that collects and studies this type of fungi.

She said she “played a little hard to get” when MIT’s Von Maltzahn came calling. “I’m really happy with the academic lifestyle and I didn’t feel the need necessarily to interact with industry,” she said.

Arnold soon was “intrigued” by Von Maltzah’s approach, which narrows down from the millions of microbes found in soil to just the ones that have migrated into plant tissue -- like the ones she found in the leaves in Panama.

Those should be the microbes the plant has “selected” as most beneficial, Indigo’s science team theorizes.

“I am really hopeful, and that doesn’t come with my experience with outside parties,” Arnold said. “That comes from my experience working with plants and microbes and recognizing the potential for what’s here.”

Scientists believe that so-called agricultural microbials offer enormous promise, though not without equally big challenges.

Evolution may be the biggest hurdle. With vast populations and fast generation times, microbes have the upper hand, warned Joel Sachs, a UC Riverside microbiologist who has studied rhizobia bacteria and pea plants.

“If you think about an evolutionary battle between a plant and bacteria, bacteria are going to win every time,” Sachs said. “There’s very little evidence, when you actually do experiments, that there’s been anything that’s really helpful” he added.

Surendra Dara, a University of California Cooperative Extension entomologist who has been seeking biological alternatives to chemical fumigants used on soil, said he has seen mixed results from experiments with several microbial treatments already on the market.

The microbes not only successfully out-competed others that are harmful to the plant, they also boosted plant growth, he said.

“Unfortunately, a lot of growers don’t have faith in these products,” he said. “A lot of scientists are getting into this area because there is some promise.”

Scientists have known since the 19th century that microbes could be beneficial to plants, not just causes of disease. They found that rhizobia bacteria, which form nodules on the roots of legumes such as beans and clover, helped convert nitrogen into a more usable form for plants in exchange for feeding off the plant’s sugars. That helped explain why crop rotation had helped keep fields fertile for centuries.

But microbes largely were left behind amid the rise of chemical fertilizers and pesticides. Those ushered in the biggest sustained expansion in food supply in human history, but left a legacy of environmental damage, including nitrates in water and toxic traces in food.

The industry has since turned back toward the soil, combing the combined plant-microbe “hologenome” for the key to fighting pests and disease. Snippets of that DNA now are routinely spliced into a plant’s genome. A gene in Bacillus thuringiensis, a soil bacterium that produces a protein lethal to several species of corn borer, has been added to corn.

But genetically modified organisms, or GMOs, have run up against suspicious consumers and food health advocates, who fear that they will introduce strains that could later prove dangerous while giving corporations a monopoly over seeds. Pitched battles over labeling such foods have been waged in several states and in Congress.

Many farmers now find themselves in an “uncomfortable position” of choosing between chemicals and GMO crops to boost yields any further, said Perry, who grew up on a farm in Tulsa, Okla.

“For the first time, farmers are sort of being vilified for their choices in how they grow their crops,” Perry said.

Sometime this year, Perry hopes to offer them an alternative that came from right below their feet.

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geoffrey.mohan@latimes.com

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