Something Funny Down on the Pharm

The battle over genetically modified food is over: Supercrops won. Now crops designed to yield drugs and vaccines have come close to slipping into our food supply. No one knows if they're safe, and everyone involved seems to have something to hide.

Last year, Curt Carlson grew drugs on his farm.

He has no idea what kind of drugs they were, because the folks who did the planting and harvesting never told him what he was growing. Carlson — 54, ruddy skin, beefy hands — has been farming in Aurora, Nebraska, since he returned from Vietnam in 1971. Four years ago, he was approached by some people who wanted to cultivate their own plants on small one- to two-acre plots in the midst of the massive soybean fields on his 1,500-acre farm. They said if he worked with them, he’d soon be able to dramatically expand production, and would, acre for acre, earn twice what he’d clear for a more conventional crop. Beyond that, though, they were pretty tight-lipped. “It’s all been kind of hush-hush,” Carlson says.

“Hush-hush,” of course, is just what you’d expect from someone growing drugs in the heartland. Except there was nothing illicit about the drugs on Carlson’s farm. Those two- acre plots had, in fact, been planted with corn — albeit corn specially engineered to grow prescription pharmaceuticals.

Venomous public debates have erupted in recent years over genetically modified (GM) crops, as engineered foods — tomatoes with genes to increase flavor, soybeans designed to resist herbicides — began showing up in grocery stores. Today, the battle over GM food is all but over in the United States: The FDA has ruled that no special labels are required to tell consumers which products contain genetically engineered crops, and 70 percent of processed foods on supermarket shelves in the United States now contain genetically engineered ingredients. But as agribusiness and government regulators argued over how much the public should know about the GM foods they’re eating, scientists were quietly developing more powerful — and some say more dangerous — plants called pharmaceutical crops (a.k.a. pharm crops), which are designed to mass-produce drugs, vaccines and industrial chemicals.

From where I sat recently in the cab of Carlson’s white pickup, his pharm plot looked like every other Nebraska cornfield in December: flat land beneath a panoramic sky, brown soil strewn with last year’s corn stubble. But his cornfield is far from average. Fields like Carlson’s are poised to revolutionize pharmaceuticals and become a multibillion-dollar industry by creating products in a way that’s cheaper, faster and safer than current methods. Pharm-raised drugs and vaccines for diseases ranging from herpes to hepatitis are entering clinical trials. And personalized cancer vaccines grown in plants may soon make it feasible to tailor cancer therapy to attack an individual’s tumor instead of wiping out his entire system with one-size-fits-all chemotherapy drugs.

But a month before I arrived at Carlson’s farm, the world was treated to a vivid demonstration of just how easily pharm crops might inadvertently slip into the food supply — which is why they’re also poised to be the center of the next great battle in the war over genetically modified crops.

PROTEINS ARE THE WORKHORSES of the human body — they’re the enzymes that digest food, the hormones that regulate growth and blood sugar, and the antibodies that battle viruses and bacteria. Most protein drugs, like Enbrel, for rheumatoid arthritis, are made by inserting a protein-
producing human gene into cultured hamster cells, which are grown in huge steel vats equipped with thousands of feet of plumbing and an automated monitoring system. Because of complex machinery and lengthy government approval processes, it can take $400 million and five to seven years to get one of these factories going.

In pharming, scientists isolate the gene for the protein they want to grow, then attach it to tiny gold beads that they shoot into a developing corn plant with a device called a gene gun. As those newly engineered plants grow, they produce corn that’s full of the protein made by their new gene. Pharmers harvest that corn and grind it, and scientists extract the pharmaceutical proteins using giant centrifuges and filtering columns. (For a variety of reasons, corn is the most commonly used pharm crop, but the process works similarly in plants from tomatoes to lettuce to tobacco.) The relative simplicity and easy scalability of such nature-based manufacturing brings a staggering potential for boosting profits: For a few million dollars, a pharm company can produce the same amount of protein each year on a 200-acre field that a pharmaceutical company could make for hundreds of millions in a factory. If a pharmer like Carlson wants to increase production, he doesn’t spend millions on machinery — he simply plants more acres.

Though no pharmed products have made it into stores yet, they aren’t far off. A company called ProdiGene — the company that’s been stocking Curt Carlson’s fields — has started marketing a corn-produced enzyme that’s used to create insulin, and other drugs have undergone early clinical tests. Furthest along is a tobacco-produced cancer vaccine made by Large Scale Biology of Vacaville, California. It creates personalized vaccines for patients with non-Hodgkin’s lymphoma by using tobacco plants to grow proteins from each patient’s cancer. Those proteins are injected back into the patient, where they trick the body into seeing the cancer cells as foreign invaders and destroying them. Such personalized medicine has long been a dream of medical researchers, who have created similar vaccines by growing tumor proteins in cell culture. That effort has never fully succeeded because of high costs and low productivity — it takes more than $10,000 and
12 months to produce a cancer vaccine using cell culture, but Large Scale Biology says it can make one in six weeks for “substantially less” in tobacco plants. Early clinical trial results, presented at the American Society of Hematology in December, show that these treatments are safe and may be effective.

Other pharmed drugs and vaccines are in clinical trials
or soon will be: corn-produced drugs for cystic fibrosis, pancreatic disease and herpes; vaccines for cholera, measles and other diseases. According to Charles Arntzen, an Arizona State University plant biologist who developed the first plant-made vaccines, 40 acres of tomatoes could produce enough hepatitis B vaccine to inoculate all newborns in China. And pharming’s potential doesn’t stop with drugs and vaccines — ProdiGene corn also grows a chicken protein for medical diagnostic kits, a biological bleach and an artificial sweetener 2,000 times sweeter than sugar. “The proteins [plants] can make are limitless,” says plant molecular biologist Roger Beachy, who runs the Donald Danforth Plant Science Center in St. Louis.

Now if only they could keep those proteins to themselves.

LATE IN THE SUMMER OF 2002, USDA inspectors examined a field just miles from Curt Carlson’s Nebraska farm, where another farmer grew a small test plot of ProdiGene corn that was engineered to make a vaccine for fighting a diarrhea-
causing virus in pigs. He’d grown the ProdiGene corn the year before, then switched his field to soybeans, which he grew for veggie burgers and infant formula. During its inspection, the USDA found a few small diarrhea-vaccine corn plants, so-called volunteer plants that had sprouted in the midst of the soybeans without being planted. The USDA, concerned that drug corn might get into the food supply, immediately told the farmer and ProdiGene to destroy the plants. For some reason, that didn’t happen — and in early October, the farmer harvested his soybeans and delivered them to the Aurora Co-op, a local grain elevator, where they were to be stored before shipping. By the time the USDA inspectors returned to the soybean field and found the remains of the volunteer corn plants mixed with soybean stubble, a few leaves and stalks from the pharm corn had contaminated 500,000 bushels of soybeans from dozens of farms — enough soybeans to fill more than 550 tractor trailers. Before the co-op started shipping them to makers of vegetable oil, soy milk and other foods, the USDA quarantined the contaminated Aurora soybeans. The news broke worldwide, and critics were outraged, blasting ProdiGene for carelessness and the USDA for lax oversight.

In December, I stood with the Aurora Co-op’s manager, Harlan Schafer, in a gravel yard as he pointed at a weathered white concrete silo as high as a 16-story building — one of several the co-op uses to store crops before shipping them. Schafer, a square-jawed 43-year-old with thinning hair and a lopsided grin, pointed to a steel ladder on the silo. “This is the elevator you saw all over the world,” he told me. On November 19, 2002, two protestors from Greenpeace climbed 100 feet up that steel ladder and hung a huge banner from a railing. The next day, newspapers worldwide carried images of the banner, which showed a giant red syringe injecting a black-and-white corncob, emblazoned with a stark message: “This is your food on drugs.”

THE GM FOODS WE EAT TODAY are usually engineered with special genes from plants or bacteria, and they’re specifically designed and tested for human consumption. Pharm crops, on the other hand, are made by inserting human and animal genes into crops. They’ve never been tested to see whether they’re safe for human consumption, because humans were never supposed to eat them. And yet, as the Aurora soybean snafu demonstrated (and as Greenpeace pointed out with its usual flair), the potential benefits of pharming come with the risk that these drug crops may someday end up in our food supply.

Especially when the crop is corn. Soybeans and other crops reproduce by themselves, pollinating their own flowers to form seeds. But corn plants use each other to reproduce, and their pollen can travel long distances to “interbreed.” That interbreeding makes corn “one of the worst crops you could possibly pick” for pharming, says Allison Snow, a plant ecologist at Ohio State University. “You cannot get 100 percent containment in corn,” Snow says. “It’s just not possible.” Even if pollen could be contained, she says, corn seed, or kernels, can sprout where they’re not wanted, as they did for Curt Carlson’s neighbor in Nebraska. Birds, deer, rivers and high wind can move corn kernels; farmers can track them into fields on their shoes. Crops like soybeans that don’t interbreed would eliminate much of that risk, as would using nonfood crops like tobacco — as Large Scale Biology does for its lymphoma vaccine. But corn continues to be the most common pharm crop, largely because it’s cheap and easy to cultivate, and it produces much more protein than alternative plants.

And so, as consumer and environmental groups fight for regulations, researchers in labs around the country are experimenting with new ways to keep pharm genes from spreading. Entire cornfields can be sterilized by having volunteers walk the rows and remove the pollen-producing male flower,
or tassel, from the top of each plant, though it’s hard to get all of them. In a recent study funded by Monsanto, which is developing its own drug corn, agronomist Gene Stevens of the University of Missouri used yellow corn as a stand-in for drug corn and white corn to represent a food crop. He wanted to test whether a yellow corn plot that was 90 percent sterilized would spread pollen to white corn. The white corn, which was planted 900 feet away — less than the quarter-mile setbacks that federal rules require — ended up with fewer than one yellow kernel per 150 ears.

Corn breeders have also bred so-called male-sterile plants that don’t shed any pollen. Other researchers are inserting foreign genes into a part of the plant called the chloroplast, which is not passed on through interbreeding. And at the insistence of the USDA, Carlson surrounds his fields with rows of corn that can’t reproduce, then beyond that with pasture grass and a quarter mile of soybeans — all planted to keep the pharmaceutical corn from spreading to nearby cornfields.

Still, critics — Greenpeace, Friends of the Earth and some of the various state Public Interest Research Groups among them — argue that it’s almost inevitable that pharmaceutical corn will one day contaminate neighboring fields whose crops are destined for, say, your morning cornflakes. Greenpeace and Friends of the Earth have called for regulators to restrict pharming to greenhouses or to ban it altogether. The food industry, which supports GM food crops when they’ve been tested for human safety, wants pharming done only in nonfood crops, calling for “zero tolerance” of crop-made drugs or vaccines in the food supply. Even the Biotechnology Industry Organization, an industry trade group, called for a moratorium on growing pharmaceutical corn in the Corn Belt — from Ohio to Nebraska — but backed down under pressure from Corn Belt politicians, who hope pharming will boost rural economies.

Pharming advocates, not surprisingly, insist that safety concerns are wildly overblown. Theoretically, they say, it’s possible that stray foreign proteins could escape into the bloodstream and trigger potentially lethal allergic reactions. But it’s far more likely that enzymes in the stomach and small intestine would chop the drug proteins into harmless pieces. Arntzen, the Arizona State University plant biologist, likens the risk of getting sick from food contaminated by pharm crops to the risk of getting struck by an asteroid: “Scientifically, I know there are asteroids circulating the universe, and there’s a possibility that one of those is going to strike the building I’m in. But I don’t run screaming from the building trying to find a safe place.”

NOT LONG AFTER his pharm corn contaminated the Aurora soybean silo, ProdiGene CEO Tony Laos — a compact, broad-shouldered man — leaned back in his chair, fixed his deep-set eyes on me, and launched into confident speculation about the future of pharming. In five years, he said, ProdiGene will sell a corn-produced HIV vaccine (a bold projection, since the yet-to-be-discovered vaccine is one of medicine’s holiest grails); in ten years, Laos says, pharming will account for about 20 percent of all pharmaceutical production — now about a $364 billion industry. But when my questions started to get specific, Laos turned wary. Could I meet with any of ProdiGene’s growers in the area? “No,” he replied flatly. Who grew the contaminated beans? “I can’t tell you that,” he said. Where is the farm located? “Nebraska.”

It’s this sort of reflexive secrecy that seems to particularly inflame pharming opponents — a secrecy not just among those producing pharmed crops, but among their watchdogs as well. After the Aurora incident, citing the need to protect ProdiGene’s confidential business information, the USDA said nothing when advocacy groups clamored to know what had been planted, where, and exactly what precautions were being taken to confine drug crops. USDA spokesman Jim Rogers, with some justification, touted the ProdiGene case as “an excellent illustration of how our regulations work,”
because the agency caught the drug corn before it entered the food supply. But if experience teaches us anything, it’s that the current USDA system will not catch every crop contamination: In 2000, an untested insecticide-producing corn called Starlink got mixed with normal corn, causing a massive recall of corn chips, taco shells and other corn products. No one was hurt, but the fiasco cost farmers and food companies
a billion dollars.

Still, pharming advocates show no signs of stopping. According to Laos, up to 10 percent of U.S. corn acres could one day be pharm corn, although other industry insiders call his estimates vastly optimistic. A glossy sales brochure put out by a seed company also owned by Laos promises pharmers a profitable future in the midst of hard times for regular farmers. The brochure’s cover sports a classic bucolic farm scene, a shiny green tractor idling next to two hoppers overflowing with corn kernels. Above them is a motto: “The Future of Corn Is Science.”

AT 6:30 A.M. the morning after my meeting with Laos, a handful of pickup trucks were already parked in the dark, cold lot at The Pantry — a diner across from Ken’s Motel on the old state road at the north edge of town. At a Formica table in the corner, seven middle-aged men leaned over their coffee talking quietly. They wore sturdy work clothes and baseball caps that said things like “Circle Seed Hybrids.” A small white marker board on the counter advertised the breakfast special: “2 eggs & tst, $1.99.”

After I asked the men about ProdiGene and pharmaceutical corn, they sat silent for a few awkward seconds, then started jawing away. Yeah, they’re all farmers, except for Kelly here who services farm machinery. What about the ProdiGene incident? “They’re just blowing it all out of proportion,” said one. Then they all started talking at once: Oh, it was just a couple of tiny corn plants in the beans, way too small to make any seed or pollen, let alone damage the beans. Besides, the leaves and stalks probably got blown out the back of the combine. Even if they didn’t, the screening system at the elevator would have caught it. “You know how the government gets,” one said.

The waitress refilled the coffee and Kelly, the biggest man at the table, sighed. “Pharmaceutical corn would probably be a good thing if they get something developed,” he said. “Might be an increase in profit or something. But they got
a long ways to go, don’t they?” The other men chuckled knowingly, and a lean, fast-talking man in a black cap smiled. “Got a long ways to go before profit now,” he said.

On December 6, Laos signed what is essentially an out-of-court settlement between ProdiGene and the USDA. In it, he agreed to undergo stricter agency oversight, to pay a $250,000 fine, and to buy back the 500,000 bushels of contaminated soybeans from the Aurora Co-op for about $3 million. The agency said ProdiGene violated its permits at three sites. One, I noticed, was a farm called Carlson Nursery.

That’s how I found my way from The Pantry out to Curt
Carlson’s farm, where I sat watching cattle nose around a water trough at the edge of a cornfield until Carlson drove up in his white pickup. He invited me into his house and told me that he and his son Cale, 25, have grown three small test plots and a 12-acre commercial production plot for ProdiGene in the past three years. The company tells them only that the corn is genetically engineered to make a protein.

Later, as we looked at Carlson’s ProdiGene plot from his truck’s cab, he described how eight ProdiGene workers picked the corn by hand, sealed it in containers, then drove off with it in a locked semi. He wanted to make one thing clear, he said: Those contaminated soybeans didn’t come from his field. “I know who it was,” he said. Then he hesitated. “But I don’t want to get anyone in trouble.”

Dan Ferber is a freelance science writer living in Champaign-Urbana, Illinois, in the heart of pharm country. He is a correspondent for Science magazine.