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A seemingly simple concept--vaccines incorporated in food--followed Arntzen home. Most vaccines are injected, but oral ones can work, like the Sabin polio vaccine introduced 42 years ago. Taking this a step further, Arntzen contemplated the possibility that plants could be engineered to produce proteins that would cause the body to produce protective antibodies. That would spare poor nations the cost of acquiring, refrigerating and transporting vials of vaccine. It would spare kids a needle in the arm.
Arntzen, now a professor of plant biology at Arizona State and director of the Arizona Biodesign Institute inTempe, is in the vanguard of the movement toward edible vaccines. He has concluded three early-stage clinical trials using potatoes bearing vaccines against hepatitis B, E. coli and the Norwalk virus, the intestinal scourge currently plaguing cruise ships. It appears that vaccine-laden food can trigger the production of antibodies, the body's virus fighters, but he has yet to prove they do so at a rate comparable to that of an injection. If all goes well, Arntzen thinks a Food & Drug Administration-approved product will be available in five years.
"We're trying to create a new paradigm. These vaccines could save millions of lives," says Arntzen. Unicef estimates 30 million infants go without basic immunizations every year. Three million of those children die from preventable diseases such as diphtheria, tetanusand measles.
Others have followed Arntzen's lead. In 1998 researchers at California's Loma Linda University reduced the symptoms of juvenile diabetes in mice by 50% after feeding them potatoes carrying insulin. Iowa State is developing corn that staves off intestinal pathogens. Meristem Therapeutics, based in France, is in clinical trials with corn geared toward cystic fibrosis. Dow Chemical (NYSE:DOW - News) and Monsanto (NYSE:MON - News) have taken a slightly different approach by looking at ways to grow antibodies in corn. San Diego-based Epicyte Pharmaceutical will begin early-stage clinical trials this year with a herpes monoclonal antibody grown in corn.
Injected vaccines are expensive--as much as $40 per dose. Arntzen believes he can eventually produce doses for pennies each, and they wouldn't need to be kept cold since they're not live vaccines. Needles, moreover, can spread other diseases if they aren't sterile. Oral vaccines work well against intestinal illnesses such as severe diarrhea, a frequent killer in the developing world. Acreage is no concern. Arntzen estimates he could vaccinate all of China against hepatitis B using 125 acres.
Despite those attributes, vaccine-bearing crops are still a hard sell. They run up against the passionate Luddite movement opposed to genetically engineered crops. The U.S. has strict regulations for growing transgenic crops to prevent cross-pollination. The European Union has gone much further in its opposition; it has halted approvals of new bioengineered foods, which would likely include those with vaccine potential.
Arntzen's entire career has prepared him to prove critics wrong. The 61-year-old grew up on a farm in Granite Falls, Minn., where his father embraced experimentation of hybrid swine and new strains of cattle. He received his Ph.D. in molecular biology fromPurdue and held positions at DuPont and the U.S. Department of Agriculture before joining Texas A&M in 1988 as its deputy chancellor of agriculture.
It was while he was there that Arntzen made his fateful trip to Bangkok. Within weeks of his return to campus, he dug up enough supporting research to conclude his dream was not so far-fetched. Scientists at Monsanto and DuPont had already proven that the genetic blueprint in corn, soybeans and potatoes could be manipulated to thwart insects or pesticides. Other studies had shown that a portion of the hepatitis B virus could be grown in yeast. "I was looking for a way to combine my agricultural expertise with human medicine," says Arntzen. "If they could grow it in yeast, I knew I could grow it in plants."
By 1993 he and some other scientists had manipulated a tobacco plant into producing the hepatitis B antigen. They moved on to potatoes, a more edible crop that's more amenable to genetic splicing.
Arntzen's process started by the rewriting of the published genetic blueprint of E. coli. He stripped out the DNA sequences that make the virus infectious to animals and replaced them with ones that made the virus more akin to those found in plants. On one end of this new genetic strand he chemically attached a promoter switch, an on-off DNA sequence that triggers a desired reaction in a cell (in this case, the production of the vaccine). After producing copies of the completed strand, he spliced them into naturally occurring pathogens called agrobacteria that are good at boring into cell walls of plants. The agrobacteria squirt the strands into the cell, where they combine with the potato's own chromosomes. With help of a growth hormone, the cell rapidly grows into cuttings large enough to plant in soil. (What was once a four-month process now takes 60 days with the advent of specialized gene-design shops.)
Arntzen conducted successful trials in 1995 on mice with these superspuds, and the next year moved with colleagues to the Boyce Thompson Institute at Cornell. But, just as his research was gaining momentum, Arntzen was sideswiped by the global revolt against genetically modified foods and struggled to raise money to conduct human trials. "Millions of people are dying not because of the [genetically modified] corn, but because they have nothing," says Kan Wang, an associate professor at Iowa State.
After seven months of waiting Arntzen finally won FDA approval for human trials. Over the next four years he fed tennis-ball-size portions of raw potatoes to 50 patients, with results that proved the vaccine would survive the trip through the digestive system and provoke an immune system response. But there was a problem: Antibody reactions among Arntzen's patients varied by as much as 30%. He had no way of equalizing doses among patients because every potato grows differently. He couldn't cook the spuds for fear of destroying the vaccine.
In 1999 Arntzen solved the dosage problem by freeze-drying slivers of potato and making an extract that could be measured. When he moved to Arizona the next year, he switched to tomatoes, which yielded easily adaptable powder or paste. And tomatoes grown in greenhouses solve environmentalists' concerns about cross-pollination of modified plants with normal ones. Arntzen admits that tomatoes may not be the answer. "Scientists will find it a fascinating task to come up with ways to get the kids to take it,"he says.
For now, Arntzen is on the road trying to raise money. He has spent $5 million on research already but needs $20 million to get through late-stage trials. One interested party is the Bill and Melinda Gates Foundation, a leader in the campaign to get vaccines to poor nations. A Gates grant would legitimize Arntzen's plant-based work. "In five years people will forget about how we manufacture this stuff," says Arntzen.