Statement of

Charles J. Arntzen, Ph.D.

President and CEO

Boyce Thompson Institute for Plant Research, Inc.

Ithaca, New York

Senate Committee on Agriculture, Nutrition and Forestry

October 6, 1999

Thank you Mr. Chairman for the invitation to appear today before the Committee. My name is Charles Arntzen. I am the President and CEO of the Boyce Thompson Institute for Plant Research (BTI), and Adjunct Professor at the College of Agriculture and Life Sciences at Cornell University. The BTI recently celebrated its 75th birthday and the 25th anniversary of our affiliation with Cornell University. We are the world's largest not-for-profit research institute devoted to the study of plants and associated organisms. Our mission is to conduct pioneering research.

I will try to make three major points in my testimony:

1. There is a pipeline of new plant products that are being created by recombinant DNA technology (genetic engineering).

2. Many of the new products are designed to directly benefit human health.

3. In addition to American producers and consumers, people in the developing world will be major beneficiaries of many of the products now under development.

My entire life has been associated with agriculture. I was born on a family farm in Minnesota at a time when my father still planted his crops using horses rather than mechanized equipment. I grew up when new technology was greatly increasing farm productivity and family-farm profitability. My education was at land grant universities, which are historically centers of agricultural innovation. My employment with USDA, academia and industry (DuPont) has been related to plant biology and crop improvement. I have attached a short curriculum vita to provide more details related to my experience and employment. I want to express my appreciation to the Committee for its support of agricultural research which has given me and my colleagues in the plant science community the ability to make discoveries leading to these enhanced crops.

New technology for agriculture has been essential for improved economics of our agricultural industry, and for improvements in both the safety and availability of our food supply. These technical advances have involved very substantial changes in both the practice of farming and the development of consumer products. An example is the introduction of soybeans as a new crop in this century. The USDA, recognizing the American need for a productive vegetable-oil crop, led United States efforts to identify soybean seeds that would be productive in the US. The USDA also led in development of process technology that was necessary to convert soybean oil and protein into high value products. Some of these technological changes lead to intense controversy, such as that which ensued after the introduction of margarine into American grocery stores. As a Minnesotan, I specifically recall the concerns that the new dairy substitute would jeopardize the livelihood of the dairy farmers in the upper Midwest, as well as statements that the new products were unhealthy in the human diet. Legislative barriers were created to protect butter sales; I remember my mother breaking color packets into the lard-like margarine blocks for color mixing when the first wave of margarine products appeared. This was the result of legislation prohibiting margarine coloration in an attempt to preserve the unique features of butter. These recollections remind me that change in the agricultural industry can lead to unreasonable concerns over potential negative impact on new technology and products.

In the last decade, a new wave of technology has begun to have an impact on American and global agriculture. This technological change is a result of our greatly increased understanding of genetics and our specific ability to utilize tools of molecular biology to understand DNA, which is the basis of all genetic traits. To a large extent, our research tools in molecular biology stemmed from medical research. The human genome project, which will identify every gene in humans, is one striking example. The needs for increased speed of DNA sequencing of human genes has lead to remarkably rapid, and increasingly simply methods for analyzing DNA and the functioning of genes in all organisms, from man to microbes. Rapid advances are being made in plant genomic research as the result of collaborative efforts of the National Science Foundation, the Department of Agriculture and Department of Energy. The impact of these new methods for crop improvement research is dramatic. Regional crop breeding stations, which previously lacked sophisticated biological style laboratories, are now adding DNA diagnostic tools that are adapted from those being introduced into hospital laboratories. Crop geneticists now use DNA marker-assisted breeding methods to speed the creation of new varieties with superior traits. (I should note that this approach does not fall under the current popular-press terminology of GMOs - genetically modified organisms - since it does not involve direct DNA manipulation in the living crop. The current terminology does not recognize genetic modifications that have been used in crop improvement over the last many decades, including hybridization, mutation breeding, and tissue culture manipulations-including haploid doubling, somaclonal selection, induction of polyploidy, and plant embryo rescue of wide hybrid crosses.)

Nearly twenty years ago, a few pioneers in crop genetics began experimenting with recombinant DNA technology. In 1983, the first success in DNA transfer into plants was reported, and a new technique was added to the crop breeder's "tool box". The concept of moving DNA was first developed by microbiologists for transfer of DNA (genes) into bacteria. The approach rapidly gained importance as a tool for pharmaceutical development and was a driving force for creation of American dominance in the biotechnology industry.

It is important to note what factors were the most important determinants of the agricultural research agenda in the U.S. in the early 1980s as recombinant DNA techniques were being developed for crop breeding. It was a period of increasing crop subsidy costs and public concern about excessive pesticide use and cropland degradation and erosion. It is therefore not surprising that the first agricultural products of recombinant DNA technology were insect-resistance seeds (Bt-corn, Bt-cotton as examples that provide farmers a means to reduce use of chemical insecticides), and crops tolerant to post emergence herbicides (which aide farmers in conservation tillage; Round-up Ready Soybeans, for example). These products have at least partially met their objectives if we judge by farm sales of the new seeds. They went through multiple years of development and testing before product launch. This timeframe is not surprising. It is a characteristic of seed improvement for food, fiber or feed crops that eight to fifteen years of time lag occurs between the first product concept and its availability to producers.

Because there are long periods of research and development that precede the introduction of any new crop involving genetic improvement, it is of value to examine the current "pipeline" to estimate the value and impact of new products. It seems certain that significant improvements in "production traits" (insect, herbicide, disease, and drought tolerance) will be available over the next decade. Other presenters to this committee will discuss these traits and their importance in strengthening American agriculture and improving the safety of our food. Since these topics are covered I will, therefore, focus my testimony on the dramatic potential of plant genetic engineering to directly benefit human health. The discussion will use a "case study" example of an area of current research that is creating a new product pipeline for plant-based oral vaccines.

Vaccines are one of the great success stories of modern medicine. Ten of millions of lives have been saved by the successful eradication of smallpox from the globe, the nearly complete eradication of polio, and the great reduction in some other infectious diseases. Using the tools of modern molecular biology, at least forty new vaccines are under evaluation. However, the likely success of immunologists in identifying new vaccine candidates has posed a problem for public health officials. They are concerned about the potential cost of "high-tech recombinant DNA" vaccines, their availability to developing countries where infectious diseases are the greatest threat, and availability of the vaccines in a convenient form for broad use. With respect to the latter issue, there has been a general call for more oral vaccines and new products that do not need costly refrigeration.

I recently authored (Appendix B) an article published in the journal Nature Medicine ("Pharmaceutical foodstuffs - Oral immunization with transgenic plants", C. J. Arntzen, Nature Medicine Vaccine Supplement, Vol. 4, pages 502-503, May, 1998.) In this publication, I document the need to develop vaccines for enteric diseases, recognizing that each year diarrhea kills about two and one-half million children under the age of five. Most of these deaths are in the developing world. Since these children and their parents are at the low end of the economic scale, little industrial research has targeted new vaccines for this public health segment. To respond to this unmet need, scientists at our institute have developed plants that contain subunit vaccines to prevent diarrheal disease. The methods involve addition of a new gene to all cells in a plant wherein this gene causes plant cells to produce a protein that holds the "fingerprint" of a human pathogen (virus or bacteria). Furthermore, subsequent generations of the plant retain this protein production capability. The protein by itself is harmless, but when plants containing it were provided as food to test animals, it acted as a vaccine dose and an immune response occurred. In the absence of disease, the animals' immune system was triggered to mount a defense against the actual disease-causing agent. (Our pre-clinical studies with animals, although intended as a component of vaccine development for humans, have revealed a new strategy for vaccination of animals. Plant-based vaccines for farm animals may provide a convenient and less costly means of preventing disease and thereby a safer food supply. For pets, the strategy could provide a less traumatic immunization.)

Since 1998, my colleagues and I have collaborated with two leading U.S. medical schools to determine if our plant-based vaccines are effective in humans. We requested and received approval from the U.S. Food and Drug Administration (FDA) to conduct human clinical trials in which volunteers consumed our genetically engineered vaccine-containing food. The results of three studies are now in hand. In every case, we have found a human immune response when volunteers simply ate raw potatoes which were engineered to contain a vaccine.

We recognize that at this early stage of our research, our plant-based vaccines are not yet a product ready for FDA approval as a prescription drug available through physicians and other health care professionals. But, the "prototype plants" we have created portend success for a novel means of both manufacturing (by growing the food crop under standard agricultural practices) and delivery of the product (in a dried food or extract using standard food processing technology).

The value of a plant-based vaccine strategy for developing countries is becoming widely accepted. The July 18, 1999 issue of the Children's Vaccine Initiative Forum summarizes the concept potential and its global importance. (The Children's Vaccine Initiative is a consortium activity of the World Health Organization [WHO], UNESCO, and philanthropic foundations.)

The WHO is organizing a conference on November 29-30, 1999 that focuses on the "exciting field of genetic manipulation of plants and animals". WHO, whose mission is to champion the health of the underprivileged, has highlighted edible vaccines as a recent advance which impacts directly on human health. (It should also be emphasized that WHO sees the benefits of plant genetic engineering for improved nutritional value of food crops - nutritional genomics - and for "bio-pharming" for development of less costly and more effective pharmaceutical products. These are other subjects of this WHO conference.)

In conclusion, I would like to emphasize several key points. Molecular genetics using recombinant DNA is a new and powerful tool for plant biologists and crop breeders, but new products created with this tool take many years to progress from the research bench through periods of extensive testing before product introduction. The very few products now available, known to the public as genetically modified organisms, represent only a fraction of the potential pipeline. The next generation of products will increasingly have direct value-added benefits for food consumers as well as the indirect value of protecting their environment (since increased productivity on existing arable land is essential to feed a burgeoning population). These enhanced crops will become mainstream products for the American agricultural industry in the next millennium, allowing it to grow in profitability and become even more robust.

This Distinguished Committee is providing a valuable service to the public by inviting independent scientists who conduct research using biotechnology to provide information that could assist the Committee and the general public in making informed decisions related to the value of new products, including those involving recombinant DNA technology. This information will allow enlightened risk-benefit analyses. The current FDA, USDA and EPA regulations that emphasize product characteristics for new foods, rather than means of creating the product, have served society well. The regulatory system we have today applies to new crops created with all means of genetic modification (including recombinant DNA techniques), and thereby assures total food and feed safety. I urge the Committee and the federal regulatory agencies to continue their world leadership in promotion of science-based regulation of our food supply, and to continue this open forum of discussion of the risk-benefits of all new technologies that become available.