Dr. Charles J. Arntzen
Department of Plant Biology, University of Arizona
Dr. Arntzen received his bachelor’s and master’s degrees from the University of Minnesota and his Ph.D. from Purdue University. He held faculty positions at the University of Illinois and Michigan State University before joining the DuPont Company in Wilmington, Delaware in 1984. Subsequently he became Director of Biotechnology in DuPont’s Agricultural Products Department. In 1988 he was appointed Dean and Deputy Chancellor for Agriculture of Texas A&M University and later served as Director of the University’s Plant Biotechnology Program and the Institute of Biosciences and Technology. From 1995 to 2000 Dr. Arntzen served as President and CEO of Boyce Thompson Institute for Plant Research which is affiliated with Cornell University. In the fall of 2000 he joined the Department of Plant Biology at Arizona State University as the Florence Ely Nelson Presidential Chair. Dr. Arntzen’s research interests have been in plant molecular biology and the utilization of biotechnology to improve food quality. He has pioneered the development of transgenic plants for production of pharmacologically active products (“edible vaccines”).
Vaccines have been enormously successful for the control of a number of important diseases affecting humans. Small pox has been eradicated and the eradication of polio is well underway. Despite these successes, vaccines have shortcomings that limit their use in third world countries. One problem is they are usually injected with needles and the inappropriate use of needles causes an estimated 1.3 million deaths each year. Fortunately the polio vaccine is administered orally. A second problem with vaccines is that they must be constantly refrigerated from the time of manufacture until the point of administration. In developing countries the cost of refrigeration represents half of the cost of vaccines. An estimated 30 to 40 percent of the world’s children are never vaccinated because the cost of vaccines is too high. The cost of measles vaccine at ten cents per dose is too expensive for use in many developing countries.
The production of vaccines has changed since the development of biotechnology. The widely used Hepatitis B vaccine can now be made from a protein found in the sticky coat of the virus particle which can be reproduced in yeast cells grown in fermentation tanks. This particular protein does not induce disease but when injected into humans it stimulates the production of antibodies and immunizes the recipient against the Hepatitis B virus. In 1991 work started on the development of vaccines in transgenic food plants to determine if vaccination might be achieved by consumption of edible plant parts. The first trials involved transgenic potato plants containing a physiologically inactive part of the toxin causing a type of diarrhea. When the potatoes were fed to mice they developed an immune response. This suggested that plant-based vaccines might be developed in plants commonly used for food.
Based on the initial studies, work was started on the development of transgenic potatoes containing the gene for the protein found in the sticky coat of the Hepatitis B vaccine. After eight years of work, a transgenic potato was developed that produced the critical protein required for a Hepatitis B vaccine. This discovery suggested that a vaccine delivery system could be developed in which people would simply eat a particular kind of potatoes to be immunized against the Hepatitis B virus.
The concept of producing vaccines in plants for the control of human diseases was immediately introduced to the Food and Drug Administration (FDA). It soon became clear to FDA that this concept involved a product that was both a food additive and a pharmaceutical. For this reason a special set of rules and regulations would be needed covering the new kind of product. FDA agreed to cooperate so that the work could move forward.
The first FDA approved tests with a Hepatitis B vaccine produced in potatoes was conducted in 1999 in one of the U.S. national vaccine testing centers. In this test 50-100 gram of raw, transgenic potatoes (doses of vaccine) were fed to volunteers who had been previously vaccinated with a conventional Hepatitis B vaccine. Blood samples drawn from each volunteer over a period of several weeks were used to quantitatively determine immune responses. It was found that levels of antibodies in people fed the transgenic potatoes were elevated to the same extent as in volunteers receiving conventional booster shots.
Following the encouraging results with potatoes, studies shifted to other kinds of food plants better adapted for production in third world countries. Because of the controversy currently associated with so-called “genetically modified foods” consideration was also given to ways in which the transgenic plants could be produced without their products entering food channels.
Last year transgenic tomatoes were developed which produced the Hepatitis B vaccine. These tomato plants produce parthenocarpic fruits. The plants produce no pollen or seeds and can only be reproduced by cuttings, thus production of such cultivars should be easily controlled. It is planned to alter the color of the fruits so they will not resemble market tomatoes. It is estimated that the cost of three doses of Hepatitis B vaccine from tomatoes will cost less than one cent in the U.S. and even less in developing countries. Other studies are being conducted with bananas because this crop can be produced in many tropical countries, consumed raw and readily fed to infants in the form of a puree. A transgenic banana has been developed that produces the Hepatitis B vaccine. The plants are being further engineered so they will have a blue flesh color making them easily distinguishable from bananas used for food purposes.
Although studies have shown that effective vaccines can be produced in transgenic plants, much additional work remains to be done. The production and delivery of vaccine-producing plants must be carefully regulated. The FDA is developing rules and regulations so that the extensive trials required for the approval of such vaccines may be conducted. No effort will be made to promote commercial use of plant-produced vaccines in foreign countries until the FDA has approved one such product for use in the U.S. Work has started in Mexico to create transgenic plants capable of producing vaccines and adapted for production there.
Other studies have been started to explore the possibilities of producing vaccines in plants that will be suitable for the control diseases of poultry, swine and other animals. This is a particularly promising area because of the need for more economical animal vaccines. Moreover such products offer a means for reducing the extensive use of antibiotics in animals feeds.
Cooperative arrangements have been developed with laboratories in other countries to further investigate the production of vaccines in plants. Organizations such as the National Institutes of Health and the World Health Organization have participated in these studies. Pharmaceutical companies have not been interested in the concept because it does not conform to their business objectives. Public institutions and philanthropic organizations have provided most of the financial support of research on plant-produced vaccines but this may change as research on vaccines for animal diseases develops.
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