It looks just like regular corn, but the ears growing in a top-secret field somewhere in the Midwest might as well moo: Their kernels contain cow DNA.
Though it sounds like the latest genetically modified frankenfood, the corn isn't meant to be eaten with butter or a dab of steak sauce. Cultivated by ProdiGene of College Station, Texas, it's the nation's first large-scale commercial crop of transgenic plants in which animal proteins are being grown for drug production. Bovine trypsin, an enzyme culled from ProdiGene's corn, is used to make insulin for diabetics. Other biopharmaceutical proteins are proving effective for treating everything from cystic fibrosis and cancer to herpes and Montezuma's revenge. Trials are in the works for dozens more therapies.
WHERE'S THE BEEF? BEING USED AS A BIOLAB INSIDE CORN.
The market for biopharmaceuticals is projected to hit $140 billion by 2020. If, that is, biopharma firms can harvest enough proteins to meet demand. Current methods are slow and costly. Since the early 1980s, companies have been successfully growing them in so-called bioreactors - cultures of microbes or mammalian cells. Bioreactor facilities can cost half a billion dollars, and it can take six months to make a designer vaccine from, say, a patient's own cancer proteins cultured in a hamster cell. Another approach: growing proteins in transgenic farm animals. But this, too, is expensive and time-consuming, and it carries the risk of transmitting livestock viruses to humans.
That's where corn and other crops come in. Flora can make the best bioreactors partly because animal proteins "are not like anything the plant needs," says Barry Holtz, founder of Large Scale Biology, a plantaceutical firm in Vacaville, California. Scientists isolate the animal genes that trigger the production of a specific protein and insert them into a plant's seed. Once cultivated, the plant produces the protein. Transgenic crops can make proteins up to 50 times cheaper, and three times faster, than standard bioreactors can. The cancer vaccine that took six months to develop in the lab might be ready in six weeks when the proteins are produced in plants - a potentially lifesaving difference. Eventually, many drugs will be made in transgenic plants, says Michael Pauly of San Diego-based Epicyte. "There are too many advantages."
There are some serious disadvantages, too. As biopharma firms move their crops from greenhouses and small outdoor plots to commercial-scale fields, the potential spread of mutant plant DNA to nearby crops looms. The proteins can be toxic to humans in large doses. You don't want interleukin-2 - a human protein that rouses the immune system but can also be lethal - in your cornflakes.
Companies are trying an array of methods to contain DNA drift. ProdiGene's cornfield is surrounded by rows of nonmodified buffer corn to capture transgenic pollen. And the farm equipment is built to prevent even a single kernel from escaping during harvest. A trained crew runs the machines, and agronomists regularly monitor the corn. Still, some critics fear that no amount of caution will do. Hence, the secrecy. "We've got to protect the fields from vandalism," says ProdiGene's John McClellan.
The USDA believes safeguards like those taken by ProdiGene are sufficient for now. But when the world is rife with crops of toxic human proteins, "we'll need better methods, and everyone is working on it," says Epicyte's Pauly. Large Scale Biology uses a transgenic virus that only temporarily alters its crops - and doesn't infect pollen. Others are looking into sterile, pollenless plants. The journal Nature recently hailed leaps in plastid technology, which produces few pollen transgenes. With such advances, LSB's Holtz predicts that investors, government, and the public will rally around the little green factories. Some giants, like Eli Lilly, already have.
Meanwhile, large-scale cultivation of drug-producing crops continues. ProdiGene will be the first to reap the rewards - the trypsin growing in its cornfield requires no clinical trials, since it won't be consumed. (It's a catalyst that helps synthesize drugs.) This year, in Clermont-Ferrand, France, Meristem Therapeutics will launch a late-stage trial for gastric lipase, a pancreatic enzyme that's absent in people with cystic fibrosis and can be grown in corn. LSB put 16 designer cancer vaccines - lymphoma fragments grown in tobacco, no less - through an early-stage clinical trial last year. It plans 100 more in 2002. Epicyte's human herpes antibody, made in corn, is in preclinical testing. An ear equals one dose. Pauly suggests you wait for the purified capsule form. It's easier to swallow.
