Statement of

Bob B. Buchanan, Ph.D.
Professor
University of California
Berkeley, California
Senate Committee on Agriculture, Nutrition, and Forestry/center>
October 6, 1999

Thank you Mr. Chairman for the invitation to appear today before the Committee. My name is Bob B. Buchanan and I am a Professor and former Chair of the Department of Plant and Microbial Biology at the University of California at Berkeley. I am especially pleased to appear before this Committee because I have been a part of agriculture all my life. I grew up on a family farm in Virginia, that my sister and I continue to own, and I have spent my entire professional career at a land grant university focusing on plant biochemistry, plant molecular biology and now plant biotechnology. I have also given professional service to agriculture in several capacities.

Today we are at the dawn of a new age in promoting and enhancing human health through the use of genetic engineering technology to improve the food choices available to the consumer. Beneficiaries of this new technology will be the consumer, the farmer and those entrepreneurial companies currently spending precious risk capital to bring these important opportunities and benefits to a commercial reality. The consumer will receive benefits not only from improved foods, but also in the areas of human and veterinary medicine.

My particular area of interest includes development of genetically engineered cereals with improved qualities such as reduced allergenicity and increased processing qualities. One vision is to generate hypoallergenic cereals such as wheat for inclusion into cereal based food products.

I would like to summarize our work, giving a snapshot to the distinguished Senators of how sustained basic scientific research may result in practical solutions to significant heretofore-unresolved problems.

The current work to reduce allergens and improve cereals was not the target of my initial research. Rather, the story begins with research initiated in Berkeley more than thirty years ago. Our early efforts led to the discovery that thioredoxin, a small protein earlier found in bacteria by others, functions in regulating photosynthesis. In fulfilling this function, thioredoxin, in effect, acts as an "eye," allowing chloroplasts, the site of photosynthesis, to distinguish light from dark. The chloroplast thioredoxin system functions by breaking critical intrachain disulfide bonds on key enzymes thereby altering their activity in the light. In this way, the plant is able to maximize the energy obtained from the sun.

As our photosynthesis findings began to be accepted and incorporated into mainstream textbooks, I considered my contribution to the field to be complete and turned my attention to the function of a different type of thioredoxin we had found to occur outside chloroplasts--i.e., thioredoxin h. This effort led ten years ago to the discovery that thioredoxin h acts as a "wake up call" in the germination of cereals. In wheat and other cereals examined, thioredoxin functions in the first few days of germination to enhance the mobilization of carbon and nitrogen and thereby nourish the new seedling. Thioredoxin acts by facilitating the degradation of protein and starch reserves. The work reported today covered thirty six years of my professional time, and more than two centuries of the collective time, energy and effort of graduate and postdoctoral students and technicians.

Research initiated soon after our entry into the cereal field prompted the realization that thioredoxin could be applied as a new tool in technology and medicine. Much of this early effort was accomplished jointly with Dr. Karoly Kobrehel, a cereal technologist at the Institut National de la Recherche Agronomique, Montpellier, France, who spent a sabbatical year in our laboratory.

In vitro studies. Research done at the biochemical or protein level has identified a role for thioredoxin in far-reaching applications. The results have opened the door to the application of thioredoxin in fields ranging from nutrition and food technology to medicine. In vitro experiments have demonstrated that thioredoxin
Alleviates food and pollen allergies,
Enhances the digestibility and nutritional quality of foods,
Improves the baking quality of poor quality flour, and
Disarms neurotoxins of snakes, scorpions and bees.

In addition, we have developed an animal model to provide the first:
Allergy test for genetically modified foods.

A unique capability of our effort involves the use of an animal model to determine whether cereals with altered thioredoxin levels have a reduced allergenicity. This is a sophisticated area of immunology. Our research with allergies stems from a collaboration with Dr. Oscar L. Frick, an allergy specialist from the School of Medicine, University of California, San Francisco. Good fortune led to me to meet Dr. Frick seven years ago and start work that has led to the discovery that treatment of major allergenic foods such as wheat, milk and soy with thioredoxin decreases their allergenicity. Dr. Frick has spent many years studying food allergy responses in humans. Most of our work has been done with an animal model that seems ideal to study human allergies. Clinical work elsewhere has extended certain of our findings to humans. The application of thioredoxin to liquid foods--milk and soymilk--will soon be turned over to a company to proceed with the further testing to develop hypoallergenic, hyperdigestible infant formulas. Work to date indicates that we can adapt our animal model to test genetically modified foods for new allergens.

Transgenic cereals. The initial work on thioredoxin h could not be extended to transgenic cereals until appropriate molecular genetic technology was developed. This is where my story intersects with another University of California researcher. Dr. Peggy Lemaux is a pioneer in developing technologies and methodologies for the transformation of cereals that can be practically reproduced and exploited in academic and industrial laboratories throughout the world. Historically, cereals were very difficult to transform and it was through the sustained efforts of individuals such as Dr. Lemaux that success was achieved. The contribution opened the door for improvement of grains through addition of thioredoxin h by using genetic engineering technologies. In collaboration with her laboratory we have generated transgenic barley lines with thioredoxin overexpressed exclusively in the grain. Ongoing studies have shown that transgenic grain have beneficial properties that we are just beginning to explore. We recently found that thioredoxin can also be overexpressed in wheat.

The availability of the transgenic barley and wheat grain has opened a new door both to study the biological role of thioredoxin and to apply thioredoxin cost effectively in technology and medicine. To this latter end we are presently formulating projects with several companies to do the research needed to facilitate technology and product movement from our laboratories to the industrial development laboratory and eventually to the marketplace at a rapid pace.

Our current transgenic cereal research program ranges from studies on fundamental seed biology to technology development and application. We wish to learn more about the function of thioredoxin by use of transgenic plants and at the same time improve the nutritional or functional properties of major foods. For example, in cooperation with Dr. Frick, we seek to gain an understanding as to how thioredoxin from our laboratory, when engineered into cereals by Dr. Lemaux's group, could benefit humans. In addition to barley and wheat, our agenda includes rice, corn, sorghum, soybean and peanuts. The practical question with respect to transgenic plants is quite simple: can the value-added properties observed with thioredoxin in vitro be conferred to transgenic seeds by the overexpressed thioredoxin h gene? If the answer is "yes," thioredoxin could have impact across the food industry.

Relevance to medicine. Another focus of our work relates to medicine. Recent work with pollen indicates that we may be able to improve the effectiveness and safety of the desensitization procedure currently used to protect against allergies. We plan to pursue this possibility by providing disarmed allergens to our animal model by injection. Human trials would follow. In a joint project with Dr. Susanne Teuber, an allergy specialist from the School of Medicine, University of California, Davis, we are also working on peanuts and tree nuts--foods that cause life-threatening allergies. This work is just getting under way but we are optimistic that we may be able to help understand why allergies to these foods are lifelong. Experiments to mitigate the allergic response to nuts are currently being planned.

Benefits. I mentioned earlier that this work has the potential to benefit the consumer, the farmer and entrepreneurial companies. Let me explain.

Consumers will benefit from these improved foods.

The American Academy of Allergy and Immunology Committee on Adverse Reactions to Food has defined food hypersensitivity allergy as "an immunological reaction resulting from the ingestion of a food or a food additive" whereas food intolerance is "a general term describing an abnormal physiologic response to an ingested food or food additive; this reaction is not proven to be immunologic."

Of all adverse reactions to food and food additives, greater than 20% are due to true "allergy" or "hypersensitivity," in which a definite immunopathologic process can be documented and a cause-and-effect relationship can be proven.

When an allergic person eats offending food, the body overreacts and releases histamine and other biochemicals, resulting in allergy symptoms which can include itchy eyes; rash or hives; runny nose; swelling of the lips, tongue, and face; itching or tightness of the throat; abdominal pain; nausea; diarrhea; and shortness of breath. In some cases, the smell or inhalation of aromas from food containing allergens is sufficient to cause a reaction. Some people have severe or anaphylactic reactions. In addition to the previously-identified symptoms, these reactions can include a dangerous drop in blood pressure and even unconsciousness. These reactions can be fatal without immediate medication and medical attention leading to about 2,500 emergency room visits and 135 deaths per year in the United States. In the United States, eight foods account for 90 percent of all allergenic reactions: milk, eggs, wheat, soy, peanuts, tree nuts, fish and shell-fish. These responses may occur within minutes or within a few hours after eating the offending food.

Conservatively, in the United States, food allergies develop in 1% and possibly as high as 3% of older children and adults and about 5 to 8% of infants and toddlers. In countries such as Japan, the incidence is much higher and is increasing. A significant percentage of these allergy problems results from allergens contained in certain cereals consumed as food. Further, airborne allergens from wheat in bakeries and confectioneries cause one of the most common forms of occupational asthma, namely bakers' asthma. Food allergies are also seen in about 10% of pet dogs and cats.

There is no cure for food allergies. Once a diagnosis is made, complete avoidance of that food is the only way to avoid symptoms. Patients must learn the scientific and technical names of foods and read ingredient labels carefully. Labels must be read before making a purchasing decision every time the patient goes to the store, because ingredients may change without warning. For example, individuals with wheat allergy must restrict their use of wheat-containing foods--a growing problem as wheat gluten is increasingly used by the food industry. In our culture, it is not uncommon for us to eat wheat at every meal, thus adhering to a wheat free diet may be difficult. There is a growing international effort to require that allergenic foods carry hypersensitivity labeling and products with cereals containing allergenic gluten (wheat, barley, rye and oats) will be affected.

It is our goal that someday food products containing cereals will be formulated with hypoallergenic grain so that persons with cereal allergies can eat a wide range of food products without fear of significant health related injuries or concerns.

Farmers will benefit from these engineered products.

In the United States the sad reality for many farmers is that the harvest price for cereals is close to the total economic cost of production. As a result, American farmers barely earn a living. When transgenic cereals can be used in high value food and animal feed owing to the presence of output traits, the premium paid for the cultivation, harvest and processing of the proprietary grains will give the farmer additional income. The increased value of the new products will make the transgenic cereals grown more than a commodity. Once it is shown that these grains can be used in high value formulated foods, the grain itself (the key ingredient) commands a premium in production. The successful completion of this project will stand as a beacon of realizable financial advantages for cereal farmers trapped with low commodity prices (often below costs) and the ebbing of critical subsidies.

Entrepreneurial companies and hence the American economy will also benefit.

Several entrepreneurial companies are currently spending precious risk capital to advance this project to a commercial reality. These companies are taking significant risks, but if the project is successful, they will benefit, and in so doing, will benefit the American economy.

Finally, let me add that diverse elements of society will benefit if this work is successful. The research to be accomplished during the next several years will potentially lead to products that will improve the quality of life across geographical and political boundaries. First, economically advanced countries will benefit through the introduction of improved foods and drinks and medical procedures to be developed through commercial channels. Once we take each to a suitable stage and learn what basic biology we can during this journey, the technologies and products will be passed on to companies for further testing and commercial development. The marketplace will be the next destination.

A second contribution of new and improved food products is for developing countries. Here we can contribute by increasing the digestibility and thereby improving the nutritional value of crops indigenous to tropical and subtropical areas--e.g., rice, one of the world's major crops, and sorghum, a cereal especially important to Africa and other parts of the developing world where corn fails to grow. Humans or domesticated animals do not digest a significant fraction of the protein of sorghum and certain rice varieties. Transforming rice and sorghum grain with the thioredoxin h gene, therefore, opens the door to increasing the dietary protein available from both foods. At the same time, it could change the world market for sorghum.

Another area in which thioredoxin may find application for developing countries relates to new food products. We have obtained evidence that thioredoxin and related natural components (NADP-thioredoxin reductase, NADPH) added in vitro, make it possible to generate new dough-like products from sorghum, corn and rice flours. Grains such as these are otherwise nonglutenous--i.e., incapable of dough formation. We are optimistic that overexpressed thioredoxin h may render these grains capable of forming new dough-based products. We plan to extend these studies during the next two years. I am in contact with the Food and Agriculture Organization of the United Nations and we also plan to select a foundation to assist with the project.

Concluding remarks. The research we are currently doing stems from studies initiated at the start of my career at Berkeley more than thirty years ago. Discoveries made on the role of thioredoxin in photosynthesis led to research that has given new insight into seed germination. Experiments built on these results suggest that thioredoxin could find broad application in technology and medicine and improve the quality of life worldwide.

In closing, I wish to commend the Committee for giving scientists an opportunity to help clarify misunderstandings surrounding genetically modified foods and to show that there is progress toward products that will benefit all of humanity. I also wish to acknowledge support from the NSF, USDA and NIH that made possible our fundamental research and to the USDA NRI which enabled Dr. Lemaux and me to start our present project on seed biotechnology. Finally, I want to mention that the lines separating these agencies are disappearing. The time is ripe for federal agencies to support cooperative programs that cut across the traditional boundaries of basic biology, agriculture, nutrition and medicine. Much of the nation's future rests on knowledge, technologies and products that will come from an integration of these diverse fields.