Uproar over diarrhea drug grown in modified rice crops

~ To date, not one biopharmed drug has come close to market approval by the FDA.

LIMA, Peru -- It should have been a triumphant moment for Dr. Nelly Zavaleta when many of the diarrhea-stricken babies she treated with an experimental U.S. drug got better quicker than expected.

Instead, one of Peru's top scientists finds herself a target of a criminal investigation, a professional ethics complaint and at the center of a global debate over food crops genetically engineered with human genes to produce drugs.

Zavaleta gave the babies an anti-diarrheal derived from rice genetically engineered to produce two key proteins in mother's milk. Last month, the Germany-based International Academy of Life Sciences, a biopharming advocate, hailed her research as a "revolutionary development."

Zavaleta's yearlong study at the Institute of Nutritional Investigation found that out of 140 babies hospitalized with serious diarrhea attacks, those given the proteins added to a standard rehydration solution recovered quicker -- 3.67 days versus 5.21 days.

The outcome is impressive, especially considering that diarrhea kills about 2 million children under age 5 every year. In Peru, it claims the lives of more than 7,000 children annually.

The experimental medicine Zavaleta administered is made by the U.S. biotechnology company Ventria Biosciences, which has amassed a large number of critics who complain it is recklessly developing a technology that threatens the safety of conventional food crops. The company had planned to grow its engineered rice in Southeast Missouri, but withdrew the plan in 2005 after protests from farmers, state legislators and Anheuser-Busch.

Many U.S. opponents, including conventional rice farmers, fear genetically engineered rice will inadvertently mix with their crops and cause them economic harm.

"It's not even just real contamination," said Rebecca Spector of the Center for Food Safety, which opposes biotechnology in agriculture. "It's also the threat of the contamination that could cause farmers to lose their markets."

Rice interests in California drove Ventria's experimental work out of the state in 2004, after Japanese customers said they wouldn't buy the rice if Ventria were allowed to set up shop.

To date, not one biopharmed drug has come close to market approval by the U.S. Food and Drug Administration.

That hasn't stopped U.S. biopharming companies from conducting clinical human trials of treatments grown in tobacco, corn and duckweed to fight everything from cancer and hepatitis C to cavities.

Ventria, a tiny Sacramento, Calif.-based firm, has defied the intense opposition, plowing ahead in North Carolina with cultivation of genetically altered rice, spliced to produce the human mother's milk proteins.

Those proteins -- lactoferrin and lysozyme -- help people hydrate and lessen the severity and duration of diarrhea attacks, Peru's second biggest killer of children under 5 and a scourge throughout the developing world.

Zavaleta's troubles don't stem from the controversy over whether food crops should be used to make medicines. They are the result, instead, of accusations she endangered her young patients' health.

The accuser is Dr. Herberth Cuba. A gynecologist, Cuba runs the small but vocal nonprofit Peruvian Medical Association, which claims without foundation to represent all Peru's licensed physicians.

Cuba complained to prosecutors that Zavaleta's experiments, in two public hospitals, were dangerous because they used "transgenetic products that haven't been approved in any nation, not even in the country of origin, the United States."

Peru was chosen for the study, he said, because it is a poor developing nation with lax enforcement of laws that Cuba insists strictly prohibit any medical experiments on children, with violations punishable by up to four years in prison.

Dr. Luis Bromley, chief of forensic investigations in Peru's attorney general's office, called Cuba's interpretation of the law wrong. Clinical trials involving children are permitted with informed parental consent and a lengthy approval process, he said.

Zavaleta maintains she adhered to all the requirements.

"All steps were followed with the ethics committees, with the approvals, with the parental consent," she said.

Dr. Justo Padilla, director of investigation at Peru's state-run Specialized Institute of Children's Health, which oversaw Zavaleta's research, said three independent scientific groups validated the research's safety before the trial began in August 2004. Among them were the Investigational Review Board at the University of California, Davis and a nine-member Peruvian ethics committee.

Nevertheless, Cuba's complaint must be fully investigated to ensure the clinical trial followed the rules to the letter, authorities say.

No matter that many in Peru's medical elite consider Cuba an irresponsible political gadfly who exaggerates facts to maximize publicity.

"He's becoming tiresome already in a situation that is alarmist and irresponsible," said Dr. Amador Vargas, dean of the Medical College of Peru, which has licensing and disciplinary oversight over the country's 46,000 physicians. The group's lawyer says Cuba faces several disciplinary charges and that his medical association has only about 200 members.

Asked for comment, Cuba replied: "They're all lies. That's all. Thank you."

Zavaleta's supporters lament how Cuba's complaint has hurt what they consider important, judicious research.

The treatment she administered could potentially put a huge dent in a chronic cycle of health problems associated with diarrhea, they believe, including malnutrition, infection, pneumonia and anemia, suffered by millions of children.

"It makes great political grist that foreigners are coming in and using genetically engineered materials on Peruvian children. That sounds pretty scary," said Dr. William Greenough III,aJohns Hopkins University professor and expert in pediatric and geriatric diarrhea.

"The fact of the matter is that we're taking purified, normal human breast milk proteins that have been exhaustively tested as to whether you could or could not even develop an%e breast milk proteins can be produced in rice at a fraction of the cost of traditional laboratory methods, putting it "within reach of kids in very poor countries."

He has developed and commercially manufactures a normal rice-based oral rehydration treatment that he says lessens diarrhea's impact but does nothing to prevent it.

Greenough said he is using one of Ventria's breast milk proteins in a U.S. study to try to halt a common diarrhea that afflicts hospitalized elderly patients when they receive large doses of antibiotics.

"So we're not testing it in Peru because we can't test it in the United States," he said. "We're testing it in both arenas."

Neither Greenough nor Ventria would provide details on the study's sample or where it was taking place. Dr. Delia Bethell, Ventria's vice president of clinical development, said results would be published next year.

Ventria's chief executive, Scott Deeter, says the anti-diarrheal treatment that proved so promising in Peru is just the beginning.

He envisions putting Ventria's transgenic products within economic reach of poor countries around the world: "Plants are the most abundant source of affordable proteins on earth, which is why they are being developed as the ideal factory for affordable health products."