May 17, 2001 NEW BRUNSWICK/PISCATAWAY, N.J. – In research that could turn Garden State farmers into highly profitable manufacturers of pharmaceuticals and other therapeutic agents, Rutgers University scientists have developed a way to use living plants to reliably and inexpensively manufacture biologically active compounds ranging from human insulin to cancer-fighting supplements.
A research group led by Rutgers Professor of Biology Ilya Raskin plans to partner with New Jersey farmers through Phytomedics, Inc., a Middlesex County company he founded in 1996, to grow plants for their therapeutic benefits rather than their food value. Dayton-based Phytomedics (phyto means "plant" in Greek) is currently training selected New Jersey farmers to use the new technology.
Raskin expects his patented technology to economically revive New Jersey farmers since they will be able to move from producing low-value food commodities to high-value therapeutic agents. "Traditional agriculture is aimed at increasing plant yields, something that's important in third world nations but no longer as important here," he notes.
In the Phytomedics product pipeline undergoing testing in animals are therapeutic compounds to fight bacteria, fungi, diabetes, cardiovascular disease, HIV, and herpes. Others under study show promise as tools to combat baldness, high cholesterol levels, and Parkinson's disease, says Raskin.
The most advanced pipeline prescription product is a botanical drug that in clinical trials has proven highly effective against rheumatoid arthritis. But the first product expected is a non-prescription anti-cancer food supplement made from a compound produced by winter cress, a leafy plant sometimes used in salads. As a non-prescription product, it won't be required to undergo the time-consuming federal approval process for prescription drugs, notes Raskin. Equally promising is Phytomedics plant manufacturing technology aimed at the market for so-called recombinant proteins, which are produced by combining genes from different species. The technology, in which recombinant genes are inserted in plant chromosomes to manufacture pharmacologically active proteins, is currently being used to induce tobacco plants to make insulin and other disease-fighting proteins.
The new technology re-connects ethical drugs with plants, their original source before synthetic drugs came to dominate the marketplace, notes Raskin. Although pharmaceutical companies have found many plant sources for drugs, the primitive bioprospecting methods used to collect them haven't changed for centuries -- essentially gathering them from plants in the wild or from cultivated fields and then grinding them up to extract their curative powers, Raskin says. However, with the new technology, the researchers have been able to turn plants into "pharmaceutical factories" that continuously supply therapeutic compounds by growing them in tightly controlled and regulated hydroponic (grown in water) greenhouses. Notes Raskin, "Plants can't run away from unfriendly environments or changing conditions so they have become chemical chameleons, making chemicals in response to these different stresses to defend themselves. Those differing chemicals are the reason why the same food plants grown under different conditions taste different."
Phytomedics technology uses this fact by "stressing" plants to induce them to make biologically active compounds in their leaves and root systems. These newly synthesized compounds, which normally help protect the plants, are extracted by removing and grinding the leaves and roots, which eventually grow back. The extracted chemicals are then tested for their disease-fighting properties.
The highly controlled greenhouse environment also eliminates a major problem for drug manufacturers – the inconsistent quality of compounds from plants grown under a wide variety of environmental conditions.
"Let's say you get an anti-fungal compound from a plant that's very active during rainy season when a lot of fungi are growing around it," notes Raskin. "A plant produces the compound to protect it from the fungal pathogens, but only when these pathogens are around."
While stressing technology offers promise, the greatest medical revolution may result from using plants to manufacture proteins – the first time proteins have been produced via plant secretion, says Raskin. Plants constantly take in chemicals or nutrients and secrete or release other chemicals or wastes into the environment. The scientist has "piggy-banked" on the secretion part of this continuous exchange to cause plants to produce proteins.
Raskin believes it will lead to inexpensive production of recombinant human proteins to combat diabetes, Alzheimer's disease, Parkinson's disease and other life-threatening ailments. He notes that a number of researchers are making proteins from plants, but the technology is expensive because it requires growing the plant, harvesting it, and grinding it up to extract the protein. "With our method, getting proteins from a plant is just like milking a cow," says Raskin. "You don't have to kill the cow, grind it up, and then extract the milk to get it -- you get it by ‘milking' the plant. And you get it continuously, over and over again."
To speed up the process of bioprospecting for promising compounds in plants from all over the world, the Rutgers/Phytomedics team has developed patented technology that uses the numbers-crunching power of computers employing so-called bioinformatics and data-mining techniques.
The technology allows the research team to rapidly compare the molecular structures of newly discovered plant compounds to known compounds in order to uncover those with therapeutic potential. This approach has reduced the time needed for identifying promising compounds from years to a few days, Raskin says.
As a result, the "hit" rate has become at least a hundred times greater than that of conventional bioprospecting, the scientist reports.
The new technology also permits his team to access close to 80 percent of the chemical diversity overlooked by conventional methods. "But we still have a long way to go," asserts Raskin, "since only a tiny percentage of the estimated 250,000 plant species in the world have been assayed."
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