Amber Waves of Drug-Producing Grain

The endless, controversial uses of biopharming

Chicago—Plants are biochemical factories fueled by sunlight that can be genetically tweaked to make whatever biomolecule is desired. And they scale up easily. If you need more of a drug, just plant more corn, barley, rice, or tobacco. Wait four months and harvest pounds and pounds of cures. That's the idea behind biopharming. Plants can produce thousands of pounds of complex low cost biomolecules that pharmaceutical chemists cannot.

The Biotechnology Industry Organization's annual convention, BIO 2006, held a panel discussion on this burgeoning industry, "Plant-Made Pharmaceuticals—Challenges and Opportunities," which included representatives from a couple of biotech companies that are using plants to produce pharmaceuticals.

The French biotech company Meristem Therapeutics produces a recombinant lipase (brand name Meripase) that helps people with cystic fibrosis to Ventria Bioscience, which has developed a variety of biotech crops that produce lactoferrin. Lactoferrin is naturally found in milk and has anti-bacterial, anti-viral, and anti-fungal properties. Ventria envisions incorporating lactoferrin in medicines to treat acute diarrhea and in topical ointments to alleviate inflammation and fight fungal infections.

Not everyone is happy with the vision of amber waves of drug producing grain. Naturally, environmental and anti-biotech activists are against them. But pillars of American business such as the Grocery Manufacturers Association of America are too. At another BIO 2006 panel, Mark Nelson, GMA's Vice President, Scientific and Regulatory Policy, declared, "Pharmaceuticals should not be produced in the food or feed crops." The beer giant Anheuser-Busch threatened to boycott rice produced in Missouri if Ventria's lactoferrin rice were grown in the state.

Both activists and food companies fear what would happen if food crops were contaminated by pharmcrops. Activists cite nebulous concerns about health effects, and grocers more concretely worry about loss of business that inevitable product recalls would cause.

Whatever one thinks about the activists' health concerns, the grocers' fear of costly and disruptive recalls is well-founded. It has happened before: Millions of dollars of products were recalled when they were discovered to contain minute amounts of the biotech insect-resistant corn variety StarLink. In October 2000, an activist lab found that StarLink, approved by the Environmental Protection Agency only for animal feed, had been detected in two brands of taco shells, prompting recalls and front-page headlines. Lost in the furor was the fact that there was little reason to believe the corn was unsafe for human consumption—only an implausible, unsubstantiated fear that it might cause allergic reactions. In the end, the U.S. Centers for Disease Control found that there was absolutely no evidence that anyone had suffered any adverse reaction to eating foods containing StarLink corn.

And then there is the Prodigene case. Prodigene produces a vaccine for pig diarrhea in corn. Prodigene contracted with a farmer in Nebraska to raise and harvest their biotech corn. The next year the farmer planted soybeans and a few volunteer corn plants sprouted. As farmers do, he harvested soybeans without worrying overmuch about the few corn plants. He delivered his 500 bushels of soybeans to a grain elevator, but when government inspectors checked it they discovered the corn. Less than an ounce of corn led them to condemn the entire elevator—500,000 bushels of soybeans. Prodigene was fined and ordered to pay for and destroy all the soybeans. In 2003, after the Prodigene fiasco, the U.S. Department of Agriculture imposed stricter isolation requirements on pharmcrops.

The BIO 2006 panel featured an Iowa farmer, Bill Horan, who contracts to grow various pharmcrops for both Meristem and Ventria. Horan's PowerPoint presentation showed the great lengths to which he goes to make sure that no pharmcrops escape his fields. For example, the Meristem lipase corn grew in a one acre plot surrounded by 100 foot swaths of fallow land in the middle of 440 acre soybean field.

Horan described the four layers of redundancy he uses to insure that no pharmagenes get out of his fields. First there is geographical separation from the nearest corn field. Second there is temporal separation: He planted the Meristem corn more than a month after neighboring farmers planted their corn. This means that the neighbors' corn will have completed pollen production and fertilization well before the Meristem corn begins to do so. Third, Meristem corn tassels (the male sex organs on corn) are sterile, so they don't produce pollen that could contaminate neighboring corn anyway. The Meristem corn is fertilized by normal commercial corn plants that are planted next to it. And fourth, even though the Meristem tassels are sterile, they are removed once the corn ears start to grow. The corn is harvested by equipment that is completely dedicated to it alone. When not in use, the equipment is locked away in a shed. The high price that Horan can charge for his pharmcrop more than justifies all the trouble and expense.

So far the total amount of land used to plant pharmcrops over the last ten years is 800 acres. One calculation assumed that 40 plant-made pharmaceuticals, worth $1 billion each, would require about 40,000 acres of land. The United States has 470 million acres of arable land. As one participant quipped, "It's not farming, it's gardening."

But do we have to use food and feed crops to produce cheap medicines? Horan insisted, "If you want to insert a gene for protein in a nonfood crop, that's a recipe for disaster. That's basically a weed and you don't know what genes it has, what it will crossbreed with, and so forth." The advantage to crop plants, said Horan, is that we know a great deal about corn. He pointed out that many crop plants simply cannot survive in the wild, and so they do not escape into the wild. "Give me a weed to grow and I can't guarantee anything," said Horan.

Yet there are ways to grow plant-made pharmaceuticals other than open fields. For example, the North Carolina biotech company Biolex Therapeutics uses the aquatic plant lemna, also known as duckweed, to manufacture human proteins like alpha interferon and human growth hormone. The Biolex lemna system is completely contained within plastic modules, and the plants reproduce clonally; that is, they don't flower and they don't pollinate, so they can't crossbreed with other plants. And no one eats duckweed. Finally, lemna plants double biomass in about 36 hours, which means that one can scale up to produce human proteins very quickly.

Plant-made pharmaceuticals by making medicines cheaper and faster could help solve all kinds of global health problems. However, if farmers and drug manufacturers want to continue to use food crops to produce medicines, there had better not be anymore cases like StarLink or Prodigene. If that happens, the public and food manufacturers will make sure that Congress and the regulators fallow their fields permanently.