Bread Could Be Back On The Menu For Millions With Gluten Intolerance

By Kate Stoll

Developing gluten-free wheat is the focus of a recent $1.1-million grant from the Washington State Life Sciences Discovery fund. Celiac disease, triggered by eating gluten proteins found in many common grains, is a genetic, autoimmune disorder, and results in painful cramps, diarrhea, and deterioration of the intestinal lining.

If Washington State University's Diter von Wettstein is successful in his goal to genetically deplete the immunogenic gluten proteins in wheat, over 24 million people worldwide diagnosed with celiac disease could again eat their favorite wheat-containing foods. Von Wettstein's work could dramatically expand the culinary options available for celiac patients whose only recourse is to completely avoid any foods containing gluten, including all wheat, barley, and rye. Unfortunately, many processed foods, such as ketchup and even ice cream, contain gluten as a thickening agent.

In addition to allowing celiac patients to eat wheat, von Wettstein predicts that his wheat will have greater nutritional value than regular wheat. Most grains do not contain sufficient amounts of the amino acid lysine, essential for a complete diet. The same proteins that harm celiac patients are particularly low in lysine. By removing the unwanted proteins, von Wettstein's wheat is predicted to have more lysine weight for weight than traditional wheat, a boon on the nutritional front.

Von Wettstein has not only orchestrated the science needed to develop gluten-free wheat, he has found three Washington farmers interested in participating in a full-scale trial. Each has celiac disease himself, so each has a personal stake in its success. Even for farmers without gluten intolerance or celiac disease, von Wettstein's specialty wheat could constitute a more valuable wheat crop. "Higher-value wheat has potential for significant economic impact" in the state of Washington, says Mark Hertle of the Life Sciences Discovery fund, adding that von Wettstein's work is an exciting combination of "fundamental genetics, agriculture, and health impacts." The promise of von Wettstein's work has attracted the collaboration of Arcadia, a biotech company in Seattle.

Von Wettstein's breakthrough approach is to reduce the harmful portion of gluten while maintaining the benign portion necessary for good bread formation. Gluten is a mixture of many proteins that fall into two categories: large glutenins, the proteins responsible for the doughiness of bread; and small glutenins and gliadins, proteins that are toxic to celiac patients. "Diter's key discovery was that a single mutation can turn off the production of the whole set of barley proteins resembling the wheat proteins that cause allergies” says Michael Kahn, professor of biological chemistry at Washington State University. The two categories of genes are turned on and off by different mechanisms in wheat, providing a clean method of turning off the immunogenic proteins while leaving the harmless and useful proteins in wheat intact. Initially, lower starch synthesis is the only downside von Wettstein predicts in his specialty wheat, but he reasons that increased lysine content will compensate in nutritional value.

Von Wettstein's methods include both traditional genetic techniques as well as TILLING(R) (Targeting Induced Local Lesions In Genomes), a newer technique to select from a set of mutations for the intended trait. One advantage to TILLING over other genetic manipulations is that it does not introduce foreign DNA, so the wheat is not considered a genetically modified organism, or GMO. Some markets will not accept GMO wheat, but TILLING for mutant strains is widely accepted.

Before joining Washington State University, von Wettstein carried out his research at the Carlsberg Laboratory for Basic Science financed since 1876 by the Carlsberg Breweries. There he and his students identified a strain of barley with characteristics similar to his specialty wheat: high lysine content and reduced immunogenic proteins. Although wheat is genetically more complex than barley, von Wettstein's success with barley provides confidence that a similar reduction in immunogenic proteins in wheat can be achieved. As Kahn says, "Diter is really good at picking problems that are solvable... he has dotted his i's and crossed his t's.”

Once the wheat is developed, the next steps include testing its acceptance by celiac patients and obtaining FDA approval. Von Wettstein expects that his specialty wheat strain could be commercially viable within the next two to three years. The possibility of eating bread and the myriad foods containing gluten without painful side effects may provide celiac patients reason for hope.

Kate Stoll is a graduate student in biochemistry at the University of Washington.

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Wheat is a staple grain in the western diet but prohibited to those with gluten intolerance. Photo: Simon Howden

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