'Pharmers' market - Biotech taking root

In a greenhouse tucked away in Indianapolis flourishes corn being engineered to provide the active ingredients in gels that fight herpes and kill sperm.

On 27 acres of Kentucky farmland grows tobacco that someday may actually help fight cancer.

And in the tiny northern California farming town of Live Oak, rice laced with disease-fighting antibiotics usually found in mother's milk sprouts on a 10-acre paddy.

It's called molecular farming, and it's blossoming at biotechnology start-ups across the country.

The idea is to implant human genes into crops to grow disease-fighting proteins, which can then be extracted and turned into profitable drugs and therapies.

Some companies trick crops into accepting human genes spliced into the plants' DNA. Seeking to produce a contraceptive, Epicyte Pharmaceuticals Inc. is splicing into corn a genetic defect found in some women with the aim of making the plant generate a protein that kills sperm.

Another company, Large Scale Biology Corp., sprays plant viruses injected with human genes onto tobacco plants; the resulting infections produce cancer-fighting human antibodies.

Could cut costs

Molecular farming offers an elementary yet revolutionary proposition: It seeks to "grow" human therapies in the fields and crack the antibody drug market, which had $2 billion in sales last year and is expected to grow to $8 billion by 2004.

Some biotech companies have been able to grow antibodies -- disease-fighting proteins that protect the body -- in labs and turn them into drugs. Proponents say molecular farming could significantly cut the costs of developing such substances.

Ten genetically engineered antibody drugs are on the market today, all developed using mice. Among the best known is Herceptin, which is used in treating some breast cancers and made by Genentech.

It took Genentech, Novartis, MedImmune and other companies decades of research and hundreds of millions of dollars to persuade the Food and Drug Administration that these drugs would not harm humans. All ten are mass-produced in state-of-the-art laboratories in huge vats -- called bioreactors -- after the antibodies have been extracted from the mice where they are manufactured.

Typically, it takes $100 million to $500 million and up to 10 years to discover, develop and deliver a single such drug.

Molecular farmers believe they can get their drugs to market for as little as $50 million by using fields instead of bioreactors to grow the raw material -- and because less costly laboratory processes could be used to refine the useful proteins for use in medicines.

"We can inexpensively produce a huge number of high quality plants to manufacture human proteins," said Robert Erwin, chief executive of Vacaville, Calif.-based Large Scale Biology.

Technological obstacles

ProdiGene Inc., based in College Station, Texas, is developing eight human therapies, including a hepatitis B vaccine. It also says it won't need an elaborate infrastructure to produce its drugs. ProdiGene's main manufacturing tool -- corn -- is fueled by sun, air and water, said its chief scientist, John Howard.

But technological obstacles loom. Few of these plant-generated proteins have been tested in people.

One of the furthest along, Large Scale Biology's non-Hodgkin's lymphoma test at Stanford University, involves just 16 subjects and is in Phase I testing, the first and smallest of the three human trials required by the FDA for any drug.

"Molecular pharmers" hope FDA approval for wider trials will be easier because their drugs don't involve another animal species, and so there is no danger of animal viruses infecting people.

But they must not only persuade the FDA that their drugs are safe and effective. They must also show the Department of Agriculture that their transgenic crops aren't likely to contaminate the food supply.

"Production of pharmaceutical compounds in crops is intriguing and possibly lucrative in the long run," said C.S. Prakash, who manages the Center for Plant Bio Research at Tuskegee University in Alabama. "It does take many years of research and the long regulatory process involving FDA and USDA to get their products out."

No formal proposals

Both agencies began meeting last summer to draw up guidelines to better regulate biotechnology farming. Nothing formal has been proposed. Currently, a USDA permit is required to grow transgenic plants outdoors, and the crops must be isolated from fields that produce food.

Activists who reject genetically modified food as unsafe -- because it is not fully understood, they say -- will be watching closely, determined to keep up the pressure for strict safety standards.

In September, Greenpeace protesters donned biohazard suits and carried 10-foot-tall syringes in front of a farm growing rice for Applied Phytologics, Inc., which is experimenting with growing human proteins found in mother's milk.

The company's USDA-approved buffer zone was a four-foot row of traditional rice, and chief executive officer Frank Hagie said the experiment wouldn't harm humans, plants or animals. But Greenpeace said the impact of the transgenic rice hadn't been studied, and contamination couldn't be ruled out.

"There are environmental concerns as well as unknown consequences," Jeanne Merrill of Greenpeace said.

Security measures

All these companies insist their technologies are safe and that they've taken every security measure possible. Large Scale Biology sprays its tobacco crop in Kentucky with the tobacco mosaic virus, which "can't be transmitted by pollen, insects or seeds," Erwin said.

ProdiGene and other companies say they control their bioengineered crops through every step of the process, from seed to harvest to disposal and field cleanup. "We have a very tight program," Howard said.

But Merrill points to the StarLink debacle last year as evidence that corporate security measures and promises don't always work. StarLink, a genetically engineered corn, won government approval as animal feed but not for human consumption.

Though StarLink was grown on less than 1 percent of the U.S. corn acreage and was thought to be tightly regulated, it nonetheless cross-pollinated widely, contaminating 430 million bushels of corn and triggering nationwide recalls of taco shells, corn chips and other foods.

"Can you imagine if sperm-killing corn got loose in the environment like that?" Merrill said.