Let There Be Light: Plant-Made Pharmaceuticals' New Home is Underground

The Next Generation of Upstream Production
Nov 01, 2004
Volume 17, Issue 11

Brent Zettl
It's not every day that a concept of utilizing an underground mine to grow pharmaceutically active plants jumps out and captures one's attention. However, in the evolution of plants becoming bioreactors for new pharmaceuticals, the concept of contained growing can be extended to consider converting hard rock mines into biosecure underground growth chambers (BUGC). These subterranean laboratory-styled chambers after they are constructed, licensed, and GMP certified, could offer a secure, year-round and cost-effective system for plant made pharmaceutical (PMP) production. This is more than just thinking out of the box; in fact it brings a whole new meaning to the "underground economy."

Larry Holbrook
A PMP production system for both R&D and commercial sales must effectively manage all the risks and costs to bring these new drugs to market. Fermentation and Chinese hamster ovary cell systems arguably work for an existing range of drugs. New drug development from a plant-based platform will require the same level of manufacturing discipline and quality control, especially with regard to: GMP compliance, regulatory approvals, high-speed throughput screening (weeks not months), security, layers of redundancy protecting the environment and the food chain, protection against foreign substances (for example, dust or pesticide residue), consistency between batch lots of production, and inventory control. Plants as bioreactors, when combined with the BUGC production system, address all these parameters.

Plant molecular farming has been touted in recent years as the next generation of biotechnology development.1,2 Recent nomenclature variants include biobased molecular production systems (BMPS) and novel protein production systems (NPPS).3 Plant bioreactors can be used for protein pharmaceuticals, industrial enzymes, unique polymers of starches and plastics, and many other speciality chemicals.

Figure 1. Growth Comparison of Tobacco Plants at Seven Weeks
Flinn and Zavon reviewed a number of upstream operational strategies for the use of plants as bioreactors.4 BUGC was developed in response to concern about PMPs and use of food or feed crops, and perceptions that enforceable regulations are not yet in place and, that environmental risk is potentially insurmountable. The operational strategy for BUGC evolved out of a background in micropropagation development, diverse crop management, and an interest in providing containment capacity for early-stage research to other plant biotechnology development.

In the early 1990s, Hudson Bay Mining & Smelting Co. Ltd. of Flin Flon, Manitoba invited Prairie Plant Systems (PPS) to explore the possibility of developing growth chambers in the unused portions (drifts) of an otherwise active mine. Miners had reported that discarded orange and apple seeds had grown to six inches in complete darkness. One of the first crops grown underground was long-stem roses. This inaugural trial produced 1,100 roses from 80 plants in 75 days, which were given to the miners (see Figure 4).

Table 1. Comparative Growth in Taxus brevifolia Plants Grown Underground (U/G) with Surface Greenhouse (S/G) over 15 Months
UNDERGROUND REAL ESTATEWith sufficient lighting, a mine offers all of the environmental parameters necessary to efficiently grow plants. Con-ceptually, a hard rock mine is underdeveloped real estate carved out of the earth. In the case of the Flin Flon, Manitoba operations, the mine space is greater than the volume of all homes for a city of one million people. The SubTerra facility at White Pine, Michigan, has been mapped at 22,500 acres (approximately 35 square miles). In terms of space, almost all the global acreage currently contemplated for PMP production could fit in these two mines alone.

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