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Gene jugglers take to fields for food allergy vanishing act

(Tuesday, Oct. 15, 2002 -- CropChoice news) --

Andrew Pollack, NY Times: The soybeans growing on a test plot in Hawaii look, grow and taste like other soybeans. But some people who eat them will notice a big difference, because the beans have been genetically engineered to cause fewer allergic reactions.

The project is one of several efforts to use genetic engineering to reduce allergies from foods like wheat, rice and peanuts. Scientists are aiming beyond food allergies, too. A group in Australia has worked on removing allergens from ryegrass, a major cause of hay fever. And at least two groups hope to genetically engineer the deadly ricin toxin out of castor plants.

One of the main concerns about genetic engineering of crops is that it might introduce new allergens into the food supply. Genetically modified StarLink corn was not approved for human consumption because scientists were concerned the bacterial protein it contained would be allergenic. When the corn was later discovered in taco shells and other foods, huge food recalls ensued.

Some researchers hope that if genetic engineering could also be used to remove allergens, it would counter some of the criticism of biotech foods. But the big-crop biotech companies are still in the very early stages of developing nonallergenic products. A spokesman for Pioneer Hi-Bred International, the big seed company growing the less allergenic soybean in Hawaii, said it might take 7 to 10 years to reach the market.

About 2 percent of adults and 8 percent of children in the nation have food allergies, causing hives, diarrhea, nausea or, in rare cases, potentially fatal anaphylactic shock. Dozens of people die each year from eating peanuts, sometimes unwittingly. Soy allergies affect fewer than 1 percent of American children, though the allergies are more prevalent in Asian countries, where soy is a staple, said Dr. Ricki M. Helm, an allergy specialist at the Arkansas Children's Hospital in Little Rock.

Nonallergenic crops could be used for special products, like soy formula for babies allergic to soy. If enough nonallergenic crops are grown, the overall level of allergens in the food supply may fall enough to limit the risks of accidental exposure.

"The ultimate goal is to make foods more safe so ingestion of hidden allergens will not cause anaphylactic or dangerous food reactions," said Dr. Helm, who is working on the less allergenic soybean with scientists from the Department of Agriculture and from Pioneer Hi-Bred and its parent company, DuPont.

Allergies occur when the body reacts to particular proteins. Genetic engineering can be used to remove, or knock out, the genes responsible for producing the allergenic proteins. One way to do this is by putting in a backward copy of the gene in question, so it cancels out the plant's own gene. Or, just putting in an extra normal copy of the gene sometimes prompts the plant to shut down both the implanted gene and its own.

To create the less allergenic soybean, the scientists removed a protein, P34, that accounts for about 65 percent of the soybeans' allergenicity. In laboratory tests, the blood of people allergic to P34 did not react with these soybeans, suggesting a successful removal.

But P34 is only one of three major allergens in soy, so eliminating it means the soy will be "marginally more safe but not completely safe," Dr. Helm said. The next step will be to eliminate the other two allergens.

One big question is whether removal of the genes will hinder the plant's ability to grow or change the characteristics of the soy. If it does, "you have a hypoallergenic seed but have no use for it," Dr. Helm said.

Dr. Elliot Herman, a molecular biologist at the Department of Agriculture and the leader of the soybean project, said extensive tests so far had not detected any problems. "Insofar as we can tell, we have removed the allergen and we've made no other changes whatsoever," he said. He said the protein was a minor component of the seed that appeared to be involved in storing energy.

Still, removing the other allergens could add to the impact. Japanese scientists have already developed a soybean lacking the two other allergens, though it still has P34. But the soybeans make hard tofu, which Japanese people do not like, said Dr. Tadashi Ogawa, a professor of agriculture at Kyoto University.

The Japanese researchers developed their soy by conventional crossbreeding because they found some naturally occurring soy without those two proteins. But neither they nor the American team could find soybeans without the P34 protein, which is why genetic engineering was required. But the fact that there are no soybeans without P34 suggests it "is very important for soybeans," Dr. Ogawa said.

In peanuts the allergy-causing proteins are such major components that eliminating them would undoubtedly alter the nut's characteristics. So scientists led by Dr. Wesley Burks at the University of Arkansas are trying instead to use genetic engineering to modify the proteins slightly so they lose their allergenicity but can remain in the peanut.

The scientists have modified the genes for two major peanut allergens so the proteins are no longer allergenic in lab tests. They then put these modified genes back into peanut plants. But so far, they have not been able to get the plants to produce the altered proteins, said Dr. Helm, who is involved in the project.

Scientists at the University of California at Berkeley have tried to make a less allergenic wheat by inserting a gene to increase production of an enzyme that breaks down certain sulfur bonds that are present in many allergens. With the bonds broken, the proteins would be more easily destroyed by stomach acids before they can provoke allergic reactions.

But Dr. Bob B. Buchanan, professor of plant and microbial biology at Berkeley, said the agricultural biotech company that had the rights to the wheat stopped working on it because times were tough for genetic engineering companies.

No attempt is being made to commercialize less-allergenic ryegrass, a major cause of hay fever, developed at the University of Melbourne in Australia. One problem with trying to use genetic engineering to reduce hay fever is that many of the pollen sources, like ragweed, are weeds. One could make a nonallergenic weed, but that would not displace the naturally occurring weeds.

Two small biotech companies, Arcadia BioSciences of Phoenix and Anawah Inc. of Seattle, have teamed up to identify and remove the genes for ricin toxin from castor plants. Separately, the Agriculture Department is working on removing both ricin and an allergen in castor plants. Several genes are involved in each, said Dr. Tom McKeon, a chemist for the department in Albany, Calif.

Ricin is one of the deadliest substances known, a potential bioterrorism weapon. Bulgarian agents killed a defector on a London sidewalk in 1978 by injecting ricin into his leg with the tip of an umbrella. The oil from castor, once infamous as a foul-tasting laxative but now mainly used as a lubricant and for other industrial purposes, does not contain the toxin. But the meal left over after the oil is extracted does, posing a risk to farmers and food processors.

"Ricin-free castor varieties address a significant national security issue," said Roy Hodges, president and chief executive of Arcadia. He and Dr. McKeon said that if the toxin could be removed, castor, which is now grown mainly in India, could once again become attractive to grow in the United States.

As the Japanese soy research shows, genetic engineering is not the only way to reduce allergens in foods. Enzymes can be used to break down the proteins in the processing of the foods. This method is already used to make some nonallergenic baby formulas and rice. The soy without two allergens developed in Japan might go on sale next year with enzymes used to destroy the third allergen, P34.

Treating people rather than the plant may be another approach. Tanox, a Houston biotechnology company, is testing a drug to lessen the severity of peanut allergies.

http://www.nytimes.com/2002/10/15/health/genetics/15ALER.html