Medicines for Agriculture

Grove of orange trees. Image by Mustafagull.

How insights gleaned from human biology can be translated into agriculture and sustainability and vice versa.

Flagship Pioneering has conceived and grown more than 100 innovative companies by translating insights from the life sciences, chemical engineering, and computer sciences into unprecedented technology platforms. For example, Repertoire Immune Medicines can create novel medicines by decoding the immune system; Cygnal Therapeutics is unlocking new therapeutic areas such as exoneural biology; and Moderna has pioneered mRNA therapeutics so that cells can produce their own drugs. Moderna’s mRNA vaccine for COVID-19, which moved from sequence selection to human trials in a record-setting 63 days, is a testament to our unique methodology for creating first-in-category life sciences companies.

Flagship’s institutional process for systematic innovation also guides the scientist-entrepreneurs who create agriculture and sustainability companies. The same spirit of origination that Flagship employs to invent innovative therapeutics is used to develop ideas and technologies that will revolutionize agriculture and reduce its environmental impact.

All over the world, farmers must produce ever-increasing quantities of high-quality products on less land. At the same time, economic and environmental pressures require them to grow those crops with less water, nutrients, and crop-protection products such as insecticides and fungicides. Today, the most pressing challenge in agriculture is how to help growers cope with a changing environment, unpredictable pest outbreaks, climate change, population pressures, and past land mismanagement, all while protecting the planet for future generations.

Flagship Pioneering’s Green Team is a multidisciplinary group of scientists, inspired by Flagship’s therapeutics platform companies to develop a new generation of cost-effective products that have faster development times, greater efficacy, and a more benign environmental impact than traditional seeds, pesticides, and herbicides. We expect our innovations to deliver extraordinary returns to growers and society as a whole, redefining agricultural practices in the 21st century.

Innovations from outside agriculture

Seres Therapeutics was founded by Flagship in 2012 to revolutionize the treatment of a wide range of diseases by modulating the function of the human microbiome. One year later, we created Indigo Agriculture with the idea that microbes are as central to the health and development of plants as they are to human health. It turns out that microbes in plants can dramatically improve crop resilience to myriad stresses, including drought, heat, cold, bacteria, fungi, and insects, and also increase crop yields. The company then connects growers and buyers directly to bring these harvests to market.

A key to crop production is the germplasm of plants—their seeds. Both annual and perennial crops need to be able to cope with environmental change as well as existing and emerging biological pests. To solve these problems, we created Inari Agriculture in 2016, which uses precision genome editing along with the latest in molecular, computational, and germplasm delivery technologies to customize the best possible germplasm for growers. Inari’s technology was made possible by insights generated by human genome editing, which was itself suggested by how bacteria defend themselves from phage attack using the natural version of CRISPR. Inari combines gene editing and rapid seed development to offer better alternatives to slow, imprecise, traditional plant breeding methods or genetically modified organisms, which suffer from regulatory burdens and consumer resistance.

Our principle in rethinking agriculture is to ask, “If an innovation is possible, will it have tremendous future value?” and feel unconstrained by current practices in industrial farming.

Biological pests reduce global agricultural output by between 20% and 30% every year. Existing crop protection practices are ineffective and can harm people and the environment. New products and delivery technologies to replace harmful pest control practices have been slow to emerge through traditional research and development. We founded Invaio Sciences in 2017 to find ways to fight insect, fungal, and bacterial pests by following cues from nature about how it controls pests. Invaio uses microbiome, symbiome, and other computationally derived targets to reduce fecundity, competitiveness, and growth of pests in ways that don’t harm the environment. Most remarkably, Invaio has developed a way to prevent citrus greening, citrus farming’s most destructive disease. Invaio’s pioneering, integrated solution delivers active compounds to the vascular systems of citrus tees to target the causative agent of the disease, Candidatus Liberibacter, and controls the populations of the psyllids that spread the bacterium by manipulating their microbiomes.

Invaio is working on even more innovative approaches. As much as 95% of agricultural products using small molecules, peptides, or nucleic acids never reach their intended targets in a crop, mostly because natural barriers in plants prevent breach of their cuticle and cell wall. However, plants communicate within their own tissues and across kingdoms using extracellular vesicles. Research into this phenomenon at Flagship suggested novel methods for delivering products to plants by natural means—a technology now being actively developed by Invaio.

Shaping agriculture with human biology

Flagship Pioneering will be creating equally innovative agricultural products and methods in the future. Scientists have understood for many years that RNA has a wide array of functions in nature, not limited to coding for proteins like mRNA, but also controlling gene expression (RNAi), remodeling the epigenome (lncRNA), and even guiding its own synthesis (snoRNA). At FL70, a Flagship Pioneering prototype company so new it has not yet been named, we are exploring a new technology derived from some of the most basic life-forms to deliver stable, active, and self-reproducing RNA. These will be able to fight off invaders, take in nutrition more effectively, and respond to a changing environment.

Our principle in rethinking agriculture is to ask, “If an innovation is possible, will it have tremendous future value?” and feel unconstrained by current practices in industrial farming. Some of our explorations can seem science fictional, like imagining ways to terraform new planets, or non-photosynthetic techniques for producing food. Others take inspiration from mechanisms being discovered in human biology, such as a new form of code for cellular information processing and subcellular metabolism. Our team of scientific advisors includes Howard Hughes Medical Institute investigators and professors Steve Jacobsen (UCLA) and Zach Lippman (Cold Spring Harbor Laboratory), who have pushed us further in our explorations.

At Flagship, we feel an urgent sense of responsibility to solve some of the world’s greater challenges, including feeding and clothing a population of billions on a planet roiled by climate change. We want to leverage breakthrough technologies from multiple fields to make the world a better place to live. Human health and society have been shaped by agriculture for millennia. Now we are exploring how we can shape agriculture with human biology.