Plant-made pharmaceuticals: progress and protests

For over a decade, researchers have devised methods for producing genetically modified (GM) plants that synthesize therapeutically active proteins and industrial chemicals, a technology known as plant molecular farming or biopharming.

Hailing the technology as the next wave in biotech, supporters claim that the biopharm industry may be worth $100 billion by 2015. This enthusiasm stems from the conviction that biopharming can provide a means to manufacture therapeutic compounds and chemicals at lower cost and in greater amounts than conventional techniques. The past half year brought signs that justify such optimism.

Accelerating advances

In June, scientists at the National Institute of Public Health in Tokyo announced their success in creating GM tobacco plant cells designed to synthesize a human recombinant monoclonal antibody that binds with hepatitis B virus. The plant-made antibodies stimulated cytotoxicity in a manner similar to anti-hepatitis B virus human antibodies used in the clinic. The National Institute’s Dr. Akira Yano told Reuters Health that, while technical problems in antibody production should be resolved in a few years, the greater challenge lies in public acceptance of plant-derived therapeutics.

The European Union has shown its interest in plant-made pharmaceuticals by investing 12 million euros for the first five years of the Pharma-Planta Consortium. Officially launched on July 12, the consortium comprises academic laboratories and industrial partners from 11 European countries and South Africa. The group aims to perfect techniques for the production of antibodies and vaccines to prevent or treat human diseases. They intend to implement the entire process of developing a plant-made therapeutic: from the design of recombinant genes to clinical trials by 2009. Pharma-Planta’s candidate plants include tobacco, maize, potatoes, and tomatoes, with a preference for plants that can express desired protein products in high quantities in easily harvestable seeds. Their first product will probably be an antibody that can be used to block HIV transmission, followed by a post-bite vaccine for rabies.

In the United States, ProdiGene Inc. (College Station, TX) announced the availability of TrypZean™, the first commercial plant-produced recombinant bovine-sequence trypsin. The company says that the enzyme, synthesized in maize, has essentially the same properties as bovine trypsin, which is used to manufacture insulin and vaccines, and to enhance wound healing. ProdiGene also produces AproliZean™, a recombinant bovine aprotinin expressed in maize. Aprotinin—an inhibitor of trypsin, plasmin and other serine proteases—can be used to reduce bleeding and provides a component in fibrin sealants. During the summer, ProdiGene requested permission from the U.S. Department of Agriculture to begin large-scale cultivation of GM corn in an area southwest of San Antonio, Texas. These fields would generate the company’s trypsin and aprotinin products.

California almost became the first state to host production-sized fields of a drug-producing food crop. Ventria Bioscience (Sacramento, CA) had applied for the go-ahead to cultivate GM rice that synthesizes the antimicrobial pharmaceutical proteins, lactoferrin and lysozyme. Although the California Rice Commission favored Ventria’s plans for a 120-acre development, the California Department of Food and Agriculture rejected the application, because the company lacked approval from federal agencies. A few months later, reports surfaced that Ventria has decided to scale back plans for production of pharmaceutical rice in California. The company intends to plant a test crop of lactoferrin-producing GM barley in Iowa, a state that does not have an established barley industry.

While many biopharming products require purification before use, edible vaccines do not. Synthesized in food crops, these vaccines employ plant components as delivery vehicles. ProdiGene recently announced a study of its edible vaccine targeted against transmissible gastroenteritis virus. The company engineered transgenic corn to produce recombinant vaccine antigens in the seed. When porcine patients ate ground corn feed that contained the vaccine antigens, they displayed an increased lactogenic immunity. Dow AgroSciences (Indianapolis, IN) shares an interest in vaccines aimed at the animal health industry. The company is building a plant-based vaccine manufacturing facility in Lincoln, NE, and plans to launch the first plant-made vaccine for the poultry industry in 2006.

Pete Siggelko, vice president of Dow AgroSciences, recently expressed confidence about biopharming during a Congressional hearing. The manufacture of “antibodies, vaccines, industrial products and pharmaceuticals is no longer a pipe dream,” he said. “It is a reality.” Not everyone wishes to see the promise of biopharming realized, however.

Arresting advances

In June, the Center for Science in the Public Interest published a report about the acceleration of biopharming’s progress. The Center observed that the USDA received 16 new applications for biopharming permits from May 2003 to April 2004, with half submitted during the last three months. The organization intended to warn about biopharming’s progress, not to praise it.

The Center’s report emphasizes that many of the USDA applicants want to plant a GM crop in a state that harbors significant commercial production of a conventional counterpart for human and animal consumption. This perceived threat against established agriculture sparked protests against GM corn in Texas and GM rice in California.

ProdiGene’s plans for large-scale production of its trypsin- and aprotinin-producing transgenic corn in Texas drew a protest from the Grocery Manufacturers of America. In a letter to the USDA, the group opined that the government provides inadequate oversight of crops engineered for pharmaceutical and industrial purposes and insisted that the FDA should evaluate the safety of the crops before they are approved for cultivation.

At the same time, consumer and environmental organizations requested California state agencies to investigate potential hazards posed by Ventria’s plan to produce pharmaceutical drugs from GM rice. The Friends of the Earth, Center for Food Safety, Consumers Union, and Environment California delivered a 22-page report detailing their concerns that the “pharmaceutical traits” of Ventria’s GM rice could pass to conventional rice through transport in the guts of birds, flooding, or pollen dispersal by bees or high winds. They also listed potential environmental impacts, such as the creation of hardier weeds and disruption of soil ecology. The groups urged California authorities to impose a moratorium on such plant-produced drugs until state agencies have conducted an independent review.

The report brought a swift rebuttal from representatives of the International Academy of Life Sciences. In a letter to California health, agricultural and environmental agencies, Drs. Hilmar Stolte (Hannover Medical School, Germany) and Robert Rich (University of Illinois, Urbana-Champaign) countered that the report does not present an objective or accurate perspective of the risks. Characterizing the document as a “laundry list of potential problems,” they accused the report’s authors of intentionally creating confusion by presenting hazards as if they were risks. “Just because a hazard can happen,” they wrote, “does not necessarily mean it will, or that it is even likely to happen.” Drs. Stolte and Rich concluded that the claimed health and environmental risks of the GM rice are negligible.

Using a different tactic to terminate Ventria’s plans, the SLO GE Free group promotes Measure Q-04, an initiative on the November ballot that would prohibit the propagation of GM organisms in San Luis Obispo County. The county Farm Bureau, the San Luis Obispo Chamber of Commerce, and academics at California Polytechnic State University oppose the measure, which they say is too broad and would chill the county’s small biotechnology industry. The notion of forbidding the growth of any GM organism is not novel. California’s Mendocino and Trinity counties have such bans in place, while Humboldt, Marin and Butte counties have measures on their November ballots that would establish similar prohibitions.

Hawai’i hosted yet another tactic for discouraging biopharm technology. In August, Judge David A. Ezra made history by ordering the USDA to identify the Hawaiian locations of four companies’ open-air test sites for food crops engineered to produce industrial chemicals and drugs. The order ensued from a lawsuit filed by Earthjustice in the Honolulu federal district court on behalf of the Center for Food Safety. The Department of Agriculture, State of Hawai’i, had denied the Center’s earlier request for this data on the basis that the records contain confidential business information protected from disclosure under federal law. According to Ezra’s order, the locations of the test fields will be revealed to Earthjustice and its client, but they must keep the information confidential for at least 90 days. During this time, the defendants can try to persuade the judge that public disclosure will result in a specific harm, such as the destruction of the fields. If the judge is not convinced, the information will become publicly available.

Representatives on both sides of the case say that this would be the first time in the United States that locations of biopharm tests would be revealed to an outside party. The decision could encourage similar disclosures in other states. The American Farm Bureau Federation’s public policy specialist, Michelle Gorman, said that her organization is concerned about the effect of the ruling on farmers. “Disclosure of the test site locations has no role in protecting public health or the environment,” she said. “To the contrary, releasing the location of the test sites could leave them vulnerable to vandalism.” The destruction of a biopharm test field not only affects farmers. Michael Rodemeyer, executive director for the Pew Initiative on Food and Biotechnology, warns that vandalism may disperse genetically engineered crops, creating the harm feared by biopharming’s adversaries.

Selected sources
Anonymous. (2004). USDA Forced to Disclose Locations of Genetically Modified Crops. August 5, 2004. Available at:

Anonymous. (2004). USDA must disclose biotech test sites. Farm Bureau News. September 6, 2004. Available at:

Hao S. (2004). USDA told to disclose “biopharm” locations. The Honolulu Advertiser. August 5, 2004. Available at:

Rauscher M. (2004). Plant-made antibody targets hepatitis B virus. Reuters Health. June 23, 2004.

Stolte H. and Rich R. (2004). Letter: Academic community supports plant-made pharmaceuticals in California. Available at:

ISB News Report

Phillip B.C. Jones, PhD., J.D.
Spokane, Washington

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(Vgl. Meldung vom 2004-09-28.)

Source Oct 11, 2004.