Though plants may hold the key to new, effective medicines, sourcing these compounds sustainably is difficult. Green Bioactives devises eco-friendly ways to produce plant-derived drugs via plant cell cultures.\n\n\n\nFor decades, the pharmaceutical industry has designed synthetic small molecule drugs and manufactured them via chemical synthesis. While this approach provides an easy way to supply medicines, it has failed to address a key problem: only a minority of drugs make it from drug discovery to the market.\n\n\n\nPlants provide new medicinal options\n\n\n\nOne way to boost the success rate of pipeline drugs is tapping into plants. These diverse organisms have evolved an arsenal of different chemicals that could reap rewards in markets including pharmaceuticals, agriculture and cosmetics. However, despite decades of pharmaceutical innovation, plants are still needed to harvest many of these chemicals.\n\n\n\n“Biochemical pathways for most plant-derived natural products are either not fully characterized ... or difficult to replicate synthetically at reasonable costs because their synthesis involves multiple low-yielding steps,” explained David McElroy, CEO of the U.K. startup Green Bioactives. He added that this lack of knowledge makes it hard to produce the chemicals in typical manufacturing systems like bacteria and yeast.\n\n\n\nHowever, sourcing directly from plants has its own disadvantages. For example, the plant-derived drug may be difficult to harvest, making it too scarce to test and commercialize at scale. Additionally, sourcing drugs from plants -- such as the chemotherapy drug paclitaxel derived from a slow-growing yew tree -- can be unsustainable in the long run.\n\n\n\nGreen Bioactives turns to plant cell cultures\n\n\n\nIn 2020, Green Bioactives was founded in the Scotland-based Roslin Innovation Centre to tackle the drawbacks of sourcing plant-derived medicines. Instead of harvesting vital substances from whole plants, the firm mass-produces them in specially cultured plant cells.\n\n\n\nPlant cell cultures allow companies to mass-produce medicines with less impact on the environment than harvesting full plants. They may also allow companies to produce complex plant-derived chemicals more easily than in microbial fermentation.\n\n\n\nAccording to McElroy, the company’s co-founder and CSO, Gary Loake, set up the company in response to high demand from customers that saw little success with other companies working with plant cell cultures.\n\n\n\nThe plant cell culture landscape\n\n\n\nPlant cells have been in development as drug manufacturing platforms for several decades. One breakthrough in the field took place in 2006, when the U.S. firm Dow AgroSciences received approval from the U.S. Department of Agriculture to market a vaccine produced in cultured cells from a type of tobacco plant. \n\n\n\nAnother big advance happened in 2012, when the U.S. Food and Drug Administration greenlit a rare disease treatment produced in carrot cells by Pfizer and the Israeli firm Protalix Biotherapeutics. Other active players in the field include the German/North American firm Phyton Biotech -- which produces paclitaxel from plant cells -- and the nonprofit Fraunhofer Institute for Molecular Biology and Applied Ecology.\n\n\n\nHow Green Bioactives stands out\n\n\n\nThere are several challenges remaining with the use of plant cell cultures. Current technologies depend on culturing a type of plant cell called dedifferentiated plant cells. These cells have a low yield and are vulnerable to stresses in manufacturing processes such as shear stress and cold storage.\n\n\n\nGreen Bioactives aims to overcome the obstacles of plant cell cultures by using a different type of culture called vascular stem cells, which the firm dissects from the leaves of whole plants. These cells have a higher yield than dedifferentiated plant cells, and are more resistant to manufacturing stresses.\n\n\n\nThe startup’s growth\n\n\n\nGreen Bioactives’ research was funded early on by the scheme Innovate UK. In December 2022, the firm bagged a seed round of £2.6 million ($3.2 million) to expand its operations and scale up its biomanufacturing approach.\n\n\n\nThe company is not limited to meeting the needs of the pharmaceutical industry: Green Bioactives is working with partners in verticals including agriculture, food and drinks and cosmetics to provide sustainable alternatives to existing production methods. \n\n\n\nThe blossoming plant cell space\n\n\n\nThere is an increasing demand for natural-derived products. However, even with advances in plant cell biomanufacturing, there remain a number of obstacles before this field can become mainstream.\n\n\n\nOne challenge is that it’s tough to tease out which compound in the plant of interest is causing a therapeutic effect. Another is that plant-based molecules don’t often fit well with traditional target assays. And assigning who owns the intellectual property for plant-based products is a thorny issue.\n\n\n\nHowever, plant cell-based manufacturing is advancing with an increasing focus on sustainability in addition to the rise of gene editing tools like CRISPR. If the field is able to overcome its limitations, it could contribute to solving many crises facing modern society including pharmaceutical commercialization, food security and climate change.