ProdiGene Field Trials of Drug- and Chemical-producing Corn

Information compiled from USDA's website for field trials of genetically engineered crops (1)

An Excel file with a complete list of ProdiGene field trials nationwide is available upon request

Possible Substances(2)

Nebraska soybeans were contaminated with engineered corn grown by ProdiGene in 2001. All of the substances involved in these trials were kept secret as confidential business information (CBI), except one that listed the substances involved as aprotinin and gp120. ProdiGene has also reported that it is growing trypsin-corn on hundreds of acres in the Midwest, including Nebraska, though for some reason this trial is not listed on the USDA's website. The ProdiGene permit for planting in Iowa in 2001 was simply listed as a pharmaceutical without further specification.

Aprotinin is a blood-clotting agent used to reduce blood loss in surgery. A version of aprotinin derived from cow lung tissue is sold by Bayer under the name of Trasylol. ProdiGene's first reported field trial of corn genetically engineered to produce aprotinin was in Nebraska in 1998. ProdiGene sees several prospective uses for its corn-grown aprotinin: as a reagent in biological research, as a blood-clotting drug, and as a built-in insecticide similar to the Bt toxins in commercialized varieties of engineered corn. Aprotinin belongs to a class of substances known as trypsin inhibitors that are known to cause pancreatic disease when fed to animals. Aprotinin has insecticidal properties as well, and has been shown to shorten the lives of honeybees that ingest it at low levels. Expert scientific advisors to the EPA have recommended that transgenic plants producing trypsin inhibitors such as aprotinin be subjected to animal feeding experiments before approval:

It is not known if the government has required any animal testing on ProdiGene's aprotinin-producing corn.

gp120 is a glycoprotein (protein with sugar groups attached) found on the surface of two strains of HIV and the closely related simian immunodeficiency virus (SIV). It is being grown in corn for possible development as an AIDS vaccine, though many researchers believe it will never be effective, and might even suppress an effective immune response in vaccinated individuals. Injection of gp120 into the brain of rats has been shown to kill brain cells, while injection into the human blood stream results in the death of white blood cells. It is not known if the USDA or FDA has conducted any environmental or health assessment of gp120-producing corn. It would seem advisable to test for possible adverse effects upon inhalation of or contact with gp120-corn dust and pollen.

Trypsin is a digestive enzyme used in biological research and pharmaceutical processing. It is traditionally obtained from cow or pig pancreas. ProdiGene announced plans to grow hundreds of acres of its trypsin-producing corn in the Midwest this year, including Nebraska, with hopes of marketing hundreds of pounds of corn-derived trypsin by year's end. Trypsin is a known inhalant allergen, causing occupational asthma in pharmaceutical and industrial workers exposed to it. Similar concerns might apply to farmers and farmworkers exposed to trypsin-corn dust and pollen, especially since trypsin is produced at very high concentrations in corn kernels. Trypsin corn is reportedly being grown under the USDA's weak "notification" system, which does not require a permit. A USDA spokesperson indicated that neither the USDA nor the FDA had conducted any health or environmental assessment of trypsin corn.

Another possible substance is laccase, an enzyme derived from a fungus. It is intended for use in the adhesives industry. ProdiGene foresees a market for corn-grown laccase that would require the planting of anywhere from 200,000 to 2 million acres of corn. A related version of laccase from the Japanese lacquer tree "may be harmful by inhalation, ingestion or skin absorption. Prolonged or repeated exposure may cause allergic reactions in certain sensitive individuals. The toxicological properties have not been thoroughly investigated."(4) Other biopharm crops reportedly grown by ProdiGene include experimental oral vaccines for hepatitis B and a pig disease, transmissible gastroenteritis. There is no indication that the USDA or the FDA has conducted any health or environmental assessment of these substances.

Endnotes

Biotech Firm Mishandled Corn in Iowa

By Justin Gillis
Washington Post Staff Writer
November 14, 2002

The biotechnology company that mishandled gene-altered corn in Nebraska did the same thing in Iowa, the government disclosed yesterday. Fearing that pollen from corn not approved for human consumption may have spread to nearby fields of ordinary corn, the U.S. Department of Agriculture ordered 155 acres of Iowa corn pulled up in September and incinerated.

The disclosure raised new questions about the conduct of ProdiGene Inc., a company in College Station, Tex., that is now under investigation for allegedly violating government permits in two states. The ProdiGene matter is proving to be a black eye for the biotech industry, which has been trying to reassure the public it can be trusted not to contaminate the food supply.

The new disclosure also is likely to have a political impact in Iowa, where politicians of both parties have been attacking a new industry-sponsored moratorium on planting genetically altered corn anywhere in the Midwest corn belt. The ProdiGene case is an example of the kind of breakdown that moratorium is meant to prevent.

Both the government and environmental groups have long been keeping watch on ProdiGene, a small privately held company pushing aggressively to turn corn plants into mini-factories to produce protein-based pharmaceutical or industrial products. ProdiGene is the only company to have entered commercial production of such a protein, an enzyme called trypsin, and it is working on many others.

In neither Nebraska nor Iowa did gene-altered corn, or soybeans growing in the same fields, enter the food supply, said Cindy Smith, acting head of biotechnology regulation for the USDA.

"It wasn't luck" that inspectors caught the problems before any unapproved products entered the food supply, she said. "It was planned luck."

She made it clear the government considers the violations significant and is weighing serious penalties. In addition, she said, the department may consider revising its rules to lessen the chance of similar problems in the future.

ProdiGene has acknowledged only "compliance challenges," releasing few details. Anthony G. Laos, the company's president and chief executive, said in a statement last night that the Iowa situation had been "fully resolved to the complete satisfaction of the U.S. government."

Before the Iowa case was disclosed, environmental groups attacked USDA officials yesterday for their handling of a problem in which 500,000 bushels of Nebraska soybeans got mixed with a small number of genetically modified ProdiGene corn plants, calling the mixing a "gross failure" of the regulatory system designed to protect the food supply. Several groups assailed the government's refusal to identify the industrial or pharmaceutical protein that may have been contained in the corn.

"There is a genetically engineered pharmaceutical or industrial chemical that mistakenly entered into the grain supply, only one stop away from getting into our food, and the government isn't talking," said Matt Rand, biotechnology campaign manager for the National Environmental Trust. "The public has the right to know what's going on."

It was unclear yesterday whether the corn involved in the Iowa and Nebraska cases was the same variety, or whether they were different varieties designed to produce two different proteins. The USDA and the Food and Drug Administration have quarantined 500,000 bushels of soybeans at a grain warehouse in Aurora, Neb., while deciding what to do.

About 500 bushels of soybeans, containing a small but detectable amount of leaves and stalks from gene-altered corn plants, were mixed into the 500,000 bushels, compromising the whole lot. USDA and FDA officials have said the beans probably will be destroyed or turned into fuel.

In both the Iowa and Nebraska cases, ProdiGene, or farmers working for the company, grew test plots of gene-altered corn in 2001. Ordinary soybeans were planted in the same fields in 2002, but a few corn seeds left over from the year before sprouted. ProdiGene was required to ensure those corn plants were removed before they could contaminate the soybeans or spread pollen to nearby cornfields, but the company failed to do so, the government has said.

In the Iowa case, the gene-altered corn may have been spreading pollen at the same time plants in nearby fields were receptive, raising the theoretical possibility that genes unapproved for human or animal consumption could have spread into ordinary field corn, the USDA said. Government inspectors therefore ordered that 155 acres of nearby corn be uprooted and burned.

Soybeans Mixed With Altered Corn

Suspect Crop Stopped From Getting Into Food
By Justin Gillis
Washington Post Staff Writer
November 13, 2002

The government has quarantined and will probably destroy hundreds of thousands of bushels of soybeans in Nebraska after inspectors found evidence that the crops were mixed with a small amount of genetically altered corn.

Inspectors for the U.S. Department of Agriculture caught the problem within 24 hours of harvest last month and stopped movement of the beans and corn before they entered the food supply, two senior government administrators said last night. But a small plot of the soybeans had been mixed at a commercial grain elevator with many bushels from other local farms. That made the entire harvest unsuitable for human consumption under government regulations.

The soybeans are thought to have been mixed with grains of corn that include a pharmaceutical or industrial protein not approved for human consumption. No one involved in the case would identify the protein in question last night, so it was unclear how harmful it might be if someone inadvertently ate it. Most proteins are rapidly destroyed in the human digestive tract, but a few can survive long enough to cause health problems.

The soybeans are likely to be burned or turned into fuel, government administrators said, and an investigation being conducted could result in civil or criminal penalties for the company, ProdiGene Inc. of College Station, Tex.

ProdiGene executives, who were attempting to reach a settlement with the government last night, issued a statement acknowledging "compliance challenges" at an unspecified company site.

"As with any new industry and new regulatory program, we can always do better," president and chief executive Anthony G. Laos said in the statement. "Working together with USDA, we intend to, now and in the future."

A senior administrator at the USDA, Cindy Smith, and another at the Food and Drug Administration, Lester Crawford, said they were highly confident that the food supply had not been affected.

The soybean mishap is reminiscent of a debacle two years ago in which a gene-altered corn variety called StarLink, which is not approved for human consumption, was used in millions of dollars worth of food products that had to be recalled.

The food industry and environmental groups have grown increasingly worried about attempts to produce pharmaceutical and industrial compounds by genetically altering plants and animals.

Much discussion has focused on the theoretical possibility that such plants could spread altered genes to food crops in nearby fields. The ProdiGene mishap also revealed that the small biotechnology companies conducting the research can't be relied upon to carry out the most elementary requirements of their government research permits, critics said.

A plot of ProdiGene test corn, genetically altered to make a protein not proven safe for human consumption, was grown on a Nebraska field in 2001. Ordinary soybeans were planted in the same field this year. Corn seeds left over from the year before sprouted and grew a small number of corn plants containing the protein. The company was supposed to check and ensure that those plants were removed before setting seed, but it did not, Smith said, even after USDA inspectors issued a timely warning.

Crawford and Smith, while acknowledging that the mishap should not have happened, said the case demonstrated that the government can regulate the new technology. Smith noted that federal law includes potentially severe penalties, including millions in fines and jail time for executives, for companies that break the rules.

"I'm very confident we can prevent these things from getting into the food supply," said Smith, acting deputy administrator for biotechnology regulation at USDA. "I think the message for us is that the system is working."

Critics were less certain.

"This technology is moving so much faster than the government is," said Jane Rissler, deputy director of food and environment programs at the Union of Concerned Scientists, an advocacy group in Washington. "So much of this regulatory scheme depends on the industry's actions, and we cannot trust them."

Much about the case remained unclear last night, including the exact size and value of the soybean crop, the location of the grain elevator in Nebraska, and ProdiGene's potential liability.

Biotech companies have learned to move genes, which encode instructions for making proteins, from one species to another. One application of the technology is to turn plants and animals into factories for growing protein-based drugs and industrial enzymes that would otherwise be expensive or impossible to produce. Even many people who see the potential benefit of the technology have argued that it should be used only in plants that are not grown as food, or in plants that don't spread pollen too widely.

The Biotechnology Industry Organization, a Washington trade group, recently announced that its members would not grow corn altered in that way in the Midwestern corn belt, or altered canola in the Canadian canola belt, a nod to food-safety concerns. Environmental groups and food processors have argued that the moratorium is too weak and that stronger government regulation is needed. Farm interests in Iowa, seeing a potentially valuable crop slip away, have complained that the policy "redlines" their state and should be scrapped.

Karil L. Kochenderfer, director of biotechnology issues at the Grocery Manufacturers of America, said last night that she was relieved the soybeans had been intercepted, but added: "This is exactly the situation the food companies have been concerned about."

U.S. Investigating Biotech Contamination Case

By Andrew Pollack
The New York Times Company
November 13, 2002

The government is investigating a case in which corn genetically engineered to produce a pharmaceutical or industrial chemical might have leaked into a batch of soybeans destined for the food supply.

Officials say they have isolated the soybeans in a grain elevator and will have them destroyed or used in a way that will not allow them to be used in food.

"Our primary concern is to make sure that nothing has entered the food or feed supply, and we're very confident about that," said Cindy Smith, acting deputy administrator for biotechnology regulatory services in the branch of the Agriculture Department that handles such matters.

Still, the case is likely to spur more concern about the technology in which plants are genetically engineered to produce enzymes to be used in manufacturing, human proteins or antibodies to be used as drugs.

In this case, ProdiGene, a company based in College Station, Tex., had grown corn containing some substance that it would not identify on a small test plot, less than an acre, in Nebraska last year. This year, the field was planted with soybeans, but some corn stalks still appeared from seed left over in the ground, which is not uncommon.

About 500 bushels of soybeans were contaminated with some of this corn, Ms. Smith said. Those soybeans, however, were brought to a grain elevator and mixed with 500,000 bushels of soybeans.

That whole amount, worth about $2.7 million, may now have to be destroyed, she said, adding that ProdiGene could face fines or penalties for not fulfilling terms of its permit requiring it to monitor its test plot carefully the following year. The company might also have to reimburse farmers and the grain elevator for their losses, she said.

FDA Orders Destruction of Soybeans

The Associated Press
November 12, 2002

WASHINGTON -- The government is ordering a biotechnology company to destroy 500,000 bushels of soybeans rather than sell them for food because they were contaminated with genetically engineered corn once grown in the same field.

None of the soybeans made it into the food supply, so there is no risk to the public, said Food and Drug Administration Deputy Commissioner Lester Crawford.

FDA will issue the destruction order to Prodigene Inc. on Wednesday.

"Prodigene is working out the terms of a program to enhance our compliance and to ensure the safest and most responsible manufacturing processes," the College Station, Texas-based company said in a statement late Tuesday. "As with any new industry and new regulatory program, we can always do better. ... We intend to, now and in the future."

The soybeans were estimated to be worth several million dollars.

The announcement comes just weeks after Prodigene joined several biotech companies in agreeing not to grow genetically engineered corn intended for drug development in places where it could contaminate neighboring fields planted with crops for human consumption. It also comes after a massive recall two years ago when the StarLink brand of genetically engineered corn, approved solely for animal feed, turned up in taco shells.

The Prodigene problem announced Tuesday is markedly different - most notably in that regulators caught the contamination before the soybeans ever made it to market, Crawford said.

Prodigene is attempting to grow different medications, from hepatitis B vaccine to an insulin-making enzyme, inside the kernels of genetically modified corn. It planted a test field in the Midwest, but the crop failed. So Prodigene plowed over the field and later planted regular soybeans intended for food, Crawford said.

Prodigene recently harvested the soybeans and discovered a few corn stalks mixed in - up to 65 grams of stalks in 500,000 bushels of soybeans, Crawford said.

Agriculture Department inspectors were on hand and notified the FDA, which on Monday impounded the crop.

The amount of contamination "wouldn't be a threat to public health, but nonetheless it wasn't supposed to be there," Crawford said.

NFPA Says Pharma-corn Incident Validates Food Industry Concerns

November 13, 2002
NFPA Media Release

(Washington, D.C.) - National Food Processors Association President and CEO John R. Cady issued the following statement in response to news that experimental corn which is genetically modified to produce pharmaceutical agents was improperly harvested and introduced to commercial storage for distribution:

The National Food Processors Association (NFPA) is the voice of the $500 billion food processing industry on scientific and public policy issues involving food safety, food security, nutrition, technical and regulatory matters and consumer affairs.

Food, Biotech Industries Feud Over Plans for Bio-Pharming

By Scott Kilman
Staff Reporter of The Wall Street Journal
November 5, 2002

CHICAGO -- A fight is breaking out between the U.S. food and biotechnology industries over plans to genetically modify food crops to make drugs and chemicals.

Bio-pharming is widely seen as the next wave for the crop-biotechnology sector, which so far has focused on making crops easier to grow.

Industry officials hope this nascent field, which exploits the ability of plants to make medically important proteins at far less expense than fermentation factories, will grow into a multibillion-dollar business by the end of the decade.

But politically powerful trade groups for the $500 billion food sector are preparing to lobby federal regulators for new rules that would make life far more difficult for bio-pharming firms. The food industry, which has been generally supportive of crop biotechnology thus far, might try to enlist consumers in its drive to take food crops out of the hands of bio-pharming businesses.

'Go to the Public'

"If need be, we could even go to the public," said Rhona Applebaum, executive vice president of scientific and regulatory affairs at the National Food Processors Association in Washington, D.C.

Most food executives have long supported the push by biotech companies into agriculture, anticipating the creation of crops that would taste better, stay fresh longer and no longer trigger allergic reactions in consumers.

But they don't want their favorite crops genetically modified for anybody else.

Many food executives are afraid that vaccines, enzymes, antibodies and hormones might accidentally end up in their products, which would trigger expensive recalls. They are worried that handling mishaps might occur and that pollen from plants designed for pharmaceutical purposes might drift far enough on the wind to impregnate related crops intended for food.

'Corn Is Protected'

"We want to ensure that our corn is protected. We are concerned," said Mark Dollins, a spokesman for PepsiCo Inc. unit Quaker Oats, which has a breakfast-cereal factory in Cedar Rapids, Iowa, a state that is spending millions of dollars to attract bio-pharming firms interested in working on corn plants, its biggest crop.

The U.S. Department of Agriculture, which has been reviewing the rules, requires bio-pharming inventors to keep their experimental crops a certain distance from fields of related plants and to time the reproductive cycle of their fields so that they are out of synch with those of neighbors' fields. But there is no limit on the geography of bio-pharming inventions or the plants that can be used.

Trade groups such as Grocery Manufacturers of America and the NationalFood Processors Association are pressing the biotechnology industry to make pharmaceuticals only from nonfood crops such as tobacco. But foodcrops such as corn, canola, potatoes, and tomatoes are the plants of choice for many bio-pharming researchers.

On The Pharm

Biotechnology firms using plants to make pharmaceuticals

Source: the companies

The biggest North American biotech trade group, the Biotechnology Industry Organization, tried to strike a compromise late last month. Its bio-pharming members, which number about a dozen in the U.S. and Canada, pledged to avoid planting corn in the major corn-producing states of Iowa, Illinois and Indiana and in portions of Nebraska and five other states.

Doesn't Cover All Food Crops

But the drug-free zone doesn't go far enough for many in the food sector. It doesn't cover all food crops, it is little more than a gentleman's agreement, and some companies interested in bio-pharming aren't members of the trade group. Iowa officials, for example, are pressing ahead with efforts to foster a bio-pharming industry built around corn, its biggest crop.

"We'll make sure Iowa is still the place to be" for biotechnology firms, Iowa Gov. Thomas Vilsack said.

Midwest economists see bio-pharming as a rare chance for a niche of farmers to reap much more money from growing corn. "The stakes are big for a place like rural Iowa," said Mark Drabenstott, an economist at the Federal Reserve Bank of Kansas City, Mo., adding: "There aren't a lot of economic opportunities that come along like this for them."

Iowa has been among the most aggressive states at trying to build a bio-pharming industry. The state has poured millions into research at its public universities, created tax incentives to lure inventors, and is proceeding with plans to build a facility for extracting pharmaceutical proteins from crops.

Recruit Meristem

One Iowa recruit is Meristem Therapeutics, a French biotechnology concern, which this year grew a one-acre test plot of corn genetically modified to make gastric lipase enzyme, which is used to treat digestive problems caused by cystic fibrosis.

Bill Horan, the Rockwell City, Iowa, farmer who grew the experimental corn, wouldn't comment on whether the project will continue in that state next year. Meristem is a member of Biotechnology Industry Organization, the industry trade group that arranged the truce. A spokesman for the organization said it expects Meristem to go along with the agreement, but officials of Meristem couldn't be reached for comment on their plans.

The accord will force ProdiGene Inc., a closely held BIO member based in College Station, Texas, to shift hundreds of acres of its genetically modified corn from one county in Nebraska, said Anthony Laos, its chief executive officer. The corn is engineered to make trypsin, a protein that is produced by the pancreas. The drug sector uses the protein to make insulin, among other things.

The trade-group moratorium is open-ended in terms of how long it lasts. But Mr. Laos said he intends to honor it for one year and then reconsider. He also is adamant about continuing to use the corn plant. Corn, he says, is one of the easiest plants to genetically modify, and it excels at making novel proteins in its seeds, a handy storage container. "We have capitulated some, but I would fight going any further," the CEO said.

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