Transforming spuds for science Vaccine: UM researchers plan to feed genetically altered potatoes to volunteers in a trial that could lead to the 'ultimate oral immunization.'

June 16, 1997|By Jonathan Bor | Jonathan Bor,SUN STAFF

With many of the world's hard-to-reach populations lacking effective vaccines, scientists are asking a novel question: Why not grow them?

In what would be the first test of an edible plant vaccine, researchers at the University of Maryland's Center for Vaccine Development (CVD) plan to feed genetically altered potatoes to human volunteers. Tests will show if the spuds succeed in tricking the immune system into mounting defenses to a common intestinal bug.

The experiment is what scientists call a "proof of principle," a first step toward judging the practical merits of an idea. Said one official at the vaccine center, "We want to see if we can get a decent antibody response with something that comes out of the garden."

If they can, researchers hope to work the same magic with bananas and other crops that are easily grown in tropical regions -- where many of the most feared diseases lurk -- and are tasty in their raw state. Cook the plant, say scientists, and destroy its power.

Years, perhaps decades, of work are needed to fine-tune plant genetics so fruits and vegetables not only stimulate the immune system -- but will produce an adequate response to protect people from getting sick. And that's assuming the idea doesn't prove wrongheaded along the way.

Despite the unknowns, scientists say the image of children eating vaccines that come from the ground is irresistible.

"It's the ultimate oral immunization," said Dr. Myron Levine, the director who founded the CVD and has become internationally known as a leader in vaccine research. "And it's as cheap as can be."

Cheap because plant vaccines would give developing countries a way to bypass manufacturing costs. Once a parent crop is created through genetic engineering, successive ones could be grown wherever the climate is right.

The trial is a collaboration with the Boyce Thompson Institute for Plant Research in Ithaca, N.Y., which conceived the idea and grew the potatoes. The university will run the clinical trial and evaluate the results.

Before tests can begin, the Food and Drug Administration must decide if the potatoes are likely to pose major safety hazards. At the CVD, scientists do not expect a problem.

"We keep scratching our heads trying to think of one," said Dr. Carol Tacket, who would oversee the trial. "It is a potato."

In a trial that could begin this summer, volunteers would eat three servings of chopped, raw potatoes over the course of three weeks. The people would be divided into three groups: Two would eat different doses of the "transgenic" spuds; a third would dine on unaltered potatoes.

Since its founding in the mid-1970s, the CVD has built a reputation for a broad approach that takes vaccine research from the laboratory to field trials in exotic locales around the world. Though its targets are diverse -- ranging from malaria to dengue fever -- the center is perhaps best known for its work on intestinal infections such as shigella, E. coli, rotovirus and cholera.

These are age-old afflictions, menacing people throughout the developing world who are exposed daily to contaminated food and water. Together, diarrheal diseases account for 2.5 million deaths annually, according to the World Health Organization.

After 20 years of research and testing, the CVD's single-dose, oral cholera vaccine is now under U.S. government review. The FDA must decide whether to license the vaccine for sale to Americans traveling abroad. Canada and several European nations have already approved it for this purpose.

In the meantime, the cholera vaccine is being tested on 67,000 volunteers in Jakarta, the capital of Indonesia. Results of that trial will have a large bearing on whether the vaccine is adopted by developing nations, where the scourge claims millions of lives each year.

Scientists such as James Kaper, who has worked on the product since 1981, hope it will replace an oral cholera vaccine that requires two or three doses and protects only about half the people who take it.

In polished new laboratories on West Baltimore Street, the CVD employs about 80 people and draws $7.6 million in annual grants and contracts. This surpasses amounts raised by such better-known parts of the University of Maryland at Baltimore as the schools of pharmacy and dentistry.

The staff includes many top scientists who said they left attractive jobs elsewhere to join the hard-driving Levine, a creative thinker who also has the diplomatic skills to work with foreign governments and advise the World Health Organization.

"His output is incredible, and he expects people to respond," said Dr. Robert Edelman, associate director for clinical research, who added that Levine is the only person he knows who can write a complicated grant proposal overnight and get it right on the first draft.

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