C&EN: COVER STORY - AGBIOTECH - Pharm Crops Complicate Issues

U sing food crops to produce pharmaceuticals adds another wrinkle to the debate over labeling and traceability of genetically modified (GM) crops. In the U.S., environmental and consumer groups and the Grocery Manufacturers Association (GMA) would like to see only nonfood crops used for the production of pharmaceuticals. This would make it easier to trace the pharmaceutical crop--so-called pharm crops--from the field to the factory and ensure that residues do not end up in the food supply.

There have also been demands for tighter government regulation of pharm crops. Some organizations, such as GMA, say federal regulations are not strong enough to prevent another contamination scare like last year's ProdiGene incident, when a corn variety engineered to produce a pig vaccine was found outside its test plots.

Cline

PHOTO BY BETTE HILEMAN

Despite the difficulties some see in trying to control such a widely grown crop as corn, there are a number of reasons why it is the genetic engineer's first choice. Molly N. Cline, director of government and industry affairs at Monsanto Protein Technologies, explains why corn is particularly well suited to the production of drugs, especially for monoclonal antibodies. Monoclonal antibodies are large complex molecules created in the cells of mammals and plants. They are used to treat a host of life-threatening and chronic diseases, including cancer, arthritis, and heart disease. Estimates are that by 2008, more than 50 monoclonal antibodies will be on the market, she says.

Several crops, including corn, tobacco, potatoes, and soybeans, have been studied as possible candidates for monoclonal antibody production, Cline explains. But corn turns out to be the most desirable for a variety of reasons. "Corn is the plant we know most about, its kernel is designed to store and accumulate large complex proteins, and pollination in corn can be controlled" so the genes from pharm corn are not likely to spread to surrounding fields, she says. Another consideration is that fewer acres are needed for large-scale antibody production because corn has a high yield.

Tobacco was considered, Cline says. But once the pharmaceutical proteins get into the tobacco leaf, they degrade. Soybeans have also been studied, but it is difficult to separate proteins from soybeans. Potatoes have been investigated. But in potatoes, the antibody protein degrades easily.

It is much cheaper to produce monoclonal antibodies in corn than in a traditional mammalian cell culture manufacturing facility, Cline says. A typical facility, using mammalian cell cultures, produces 500 kg of antibody per year and costs $450 million. The same amount of antibody could be produced in 500 acres of corn and processed in a facility costing only $80 million, she explains.

Monsanto is conducting field trials with antibody-producing corn in a very confined way, Cline says. All trials are conducted outside major corn-producing areas. No crop is grown within a mile of the test plot. The trial plants are detasseled so they cannot pollinate conventional fields. The farmer who grows the pharm crop is not allowed to plant a food or feed crop in the test plot area or the 50-foot fallow zone surrounding it the next year. And Monsanto has to maintain a chain of custody for the entire trial crop.

In addition, dedicated mechanized equipment is used for growing and storing the pharm corn. The corn is grown, handled, and transported in a closed-loop, traceable system, "completely separate from and outside of commodity grain channels," she says. Monsanto conducts a "significant number of field site inspections of every trial plot to verify compliance with the regulations," she explains. U.S. regulators have adequate authority to regulate pharm plants, she concludes.

Kochenderfer

PHOTO BY BETTE HILEMAN

Karil L. Kochenderfer, coordinator of biotechnology at GMA, points out, however, that despite the many advantages of producing drugs in crops, pharm crops do present possible risks to public health and financial risks to food producers. If pharm crops contaminate the food supply, as nearly happened in the ProdiGene incident (see page 30), this could lead to product recalls, brand name risks, and loss of consumer confidence, she says.

"Pharming is open-air drug manufacturing," she says, "and needs to be regulated as tightly as the brick-and-mortar counterparts." A "science-based, coordinated, comprehensive" system for pharm crops needs to be set up, she says. "Permit controls need to be established and policed by USDA with FDA safety review and input into the process," she explains.

There needs to be increased government oversight and enforcement of USDA permit requirements at every step of the growing and manufacturing process for pharm drugs, Kochenderfer says. In addition, there should be chain-of-custody documentation at every step of the way and waste disposal should also be tightly regulated, she says. USDA and FDA enforcement needs to be heightened "at critical control points in the production and harvesting of pharm crops," she notes.

Until the U.S. government promulgates mandatory, science-based regulations that prevent the inadvertent or intentional contamination of the food supply, "it should not permit the use of food crops or crops that are sexually compatible with food crops in the manufacture of pharmaceutical or industrial compounds," she states.

Gregory Jaffe, director of the biotechnology project at the Center for Science in the Public Interest, concurs. "The current federal regulatory system does not ensure thorough environmental assessment before the planting of pharm crops, nor does it adequately prevent these crops from contaminating the food supply," he says.

"Congress, FDA, and USDA need to set forth a rigorous and robust regulatory system that ensures both and human and environmental safety from this technology," Jaffe says. Some of the regulatory changes Jaffe favors are embodied in the Genetically Engineered Foods Act (S. 3095) introduced by Sen. Richard J. Durbin (D-Ill.) last year.