It is important for the State of Iowa to respond to the draft guidance from BIO concerning "Plants Intended Not to Be Used for Food or Feed." The guidance impacts Iowa because our state has been a leader in the production of plant-made pharmaceuticals (PMPs) and this technology has great economic potential. Industry estimates are that PMP production may be a $12-14 billion industry by 2005 (Datamonitor; Arthur D. Little; AgIndustries Research and Consulting.)
We support the view of BIO and others that our highest priority is to safeguard Iowa's enormous agricultural resource and to maintain public confidence in the quality and safety of our food supply. At the same time, Iowa cannot and should not be denied the opportunity to benefit from the promise offered by the production of PMP crops - often called "biopharming." We are resolute in the conviction that biopharming can be conducted in a safe, well-managed and environmentally-friendly way - compatible with the best interests of our commodity agriculture.
A common perception about biopharming is that it is and will be a small enterprise, limited to small acreages, advantaging a few and putting the majority at risk. Another view, however, is that biopharming will become a major enterprise in the State, because biopharming is not just limited to "high end" pharmaceuticals or nutraceuticals, but includes the production in plants of a wide variety of industrial products, not intended for food or feed. For example, ProdiGene, one of the rising companies in this industry, lists, in addition to vaccines and antibodies, industrial enzymes and nonclinical products targeted for production in plants(http://www.prodigene.com). Industrial enzymes include products such as laccase, trypsin and redox enzymes and non-clinical products such as aprotinin and avidin. In addition, other industries may be interested in large-scale production of commodity crops that have been modified for fuel and/or fiber production. Thus, the magnitude of possibilities for growing crops not intended for food and feed exceed common perceptions about the future range and scope of biopharming.
What is most disconcerting about the BIO draft guidance is that Iowa has made great progress recently in introducing good biopharming practices to the state. William and Joe Horan in Fort Dodge, Iowa, have been real pioneers in this area by operating the first farmer-owned biopharming enterprise in the nation. The Horan brothers have grown a small pharmaceutical-producing corn crop for the past two years on a large (4000 acre) farm devoted to specialty and commodity production. The Horan farm is a model biopharming operation demonstrating that biopharming is compatible with production agriculture.
Biopharming is the production of a specialty crop and many Iowa farmers are experienced in the production of non-biotech crops conventionally bred for specific user needs. An example is soybeans bred to produce higher levels of a desirable fatty acid, such as oleic acid, in its oils. These crops often command premium prices and are handled separately and sold on contract.
In contrast to specialty crop production, the major concern about biopharming is its containment -- preventing the adventitious presence of biological material used in pharmaceutical production in the food, feed or seed supplies. Unlike transgenic crops that have been approved for human food consumption, PMP crops are intended for very special uses and the appropriate safeguards must be in place to prevent the unintended release of these materials into the environment or the commodity stream. The safeguards include methods for containment of crops and preservation of identity of the materials in production and processing procedures.
In general, there are two types of containment for PMP crops -physical and biological containment. Physical containment involves isolating the crop and keeping the product or seed from contaminating other materials. Biological containment uses biological processes to prevent seed or pollen from dispersing and/or propagating. Biological containment can be represented by strategies used in hybrid corn production such as male sterile corn. However, many new biological containment strategies have been devised and several were described recently by Daniell (2002). Both physical and biological containment techniques have been employed very successfully for nearly a quarter of century in research and industry that use recombinant microorganisms.
The question posed by the BIO draft guidance is how much physical containment is needed to grow PMP producing crops safely and can that be done in the CornBelt? At the heart of the issue are matters pertaining to pollen dispersal or drift. This is the major reason why BIO has advised against the growth of regulated articles that are derived from outcrossing food and feed crops in areas of the country that are centers of that crop's production. Pollen dispersal has been studied extensively by the seed corn industry, and there are number of investigations in the public domain. One report from Jemison and Vayda (2002) states that "Critics of GE (genetic engineering) frequently refer to 'gene clouds' of mutant corn pollen traveling distances of many miles to cross-pollinate and contaminate non-GE corn." That is simply not the case. Corn pollen is one of the heavier pollens produced by wind pollinated plants and the distance that it travels under various wind condition has been extensively studied. Despite the variability of wind conditions, patterns of corn pollen dispersal are definable because corn pollen is short-lived, surviving only for minutes or hours on hot dry days (Purseglove, 1972).
Some the studies of corn pollen dispersal are described at BIO's own website. One is a recent paper by Stevens et al. (2002) who examined the spread of pollen using simple, reliable markers. They examined the dispersal of pollen from a yellow-kernel inbred to a white-kernel hybrid. The yellow-kernel pollen source was planted in a 10-acre block in the middle of a 160-acre cotton and bean field and at various distances from the block four-row strips of white-kernel hybrid were sown at various planting dates. In addition, the yellow kernel inbreds were marked with distinguishing molecular markers and were detasseled to various extents - removing 0%, 80%, 90% and 100% of tassels. The upshot of the study was that pollen dispersal dropped as distance and detasseling increased. At distances less than those prescribed by APHIS (USDA Agricultural Pest and Health Inspection Service) for the separation of PMP from conventional corn (900 ft), Stevens et al. found only a 0.0013% incidence of contaminant kernels from the 90% detassled pollen source and 0.0% incidence from the 100% detasseled pollen source. No contamination was observed in comparable studies in Missouri, California and in Washington state.
Conventional crops can be further protected by "stacking" containment strategies for PMP crops. Stacking several independent containment strategies can reduce the risk of contamination to negligible levels, because the overall risk is the product of the individual risks. The measures taken to contain the PMP corn crop by the Horan Brothers is a good example of stacking containment strategies. The Horans worked closely with the APHIS to develop the strategies for their particular operation. Their strategies include:
BIO should promote biopharming in the Midwest by building on the successes of operations, such as the Horan Brothers. The Horans have provided testing grounds to examine PMP production at all levels -- from site preparation, planting, harvesting, equipment use and product handling and distribution. In addition, they have developed standard operating procedures and verification practices through documentation and record keeping. This experience has been invaluable to everyone involved in the regulation and oversight of the process as well as to others along the production chain.
To grow biopharming practices properly in the Midwest, we need to intensify research in this area and develop systems to ensure the flawless execution of the technology. We feel that the regulatory oversight from APHIS and other responsible federal agencies is serving us well in promoting the technology and protecting our commodity agriculture and environment. Unlike, biotech products intended for food or feed, PMP crops will not be deregulated, but will kept under the scrutiny of federal regulators. In addition, other safeguards such as seed certification systems will assure the safety and integrity of our seed supply. However, other good practices should be put in place outside of the federal and state regulatory arena. For example, certification systems are needed to certify growers, distributors and processors. Many Iowa producers, distributors and processors have become ISO9000 certified, but further certification systems should be required for anyone involved in biopharming practices.
We need to realize from the outset that no system will be absolutely failsafe for the Midwest, even if the restrictions of the BIO draft guidance stay in place. However, we need to strive toward no-risk practices but be prepared to manage incidences when they occur. We feel that can best be done in the Corn Belt under the watchful eye of regulators, farmers, educators and industry. We all have been sensitized to and educated by the Starlink incident. Starlink was a wakeup call to warn us that systems were not in place to handle specialty crops not intended for human consumption. We have taken many actions to make sure that a Starlink will not happen again.
Finally, we urgently need to support research to make sure that biopharming can be conducted in Iowa in a safe, responsible, well-managed and environmentally friendly manner. Research can address many of the difficult biopharming problems - not the least of which is finding a better crop to use for producing PMPs. In addition, we need to support risk analysis research to define and evaluate the risks and the benefits associated biopharming and new technologies that might be advanced in this area.
Biopharming is a great opportunity for Iowa. We should not shrink from the challenge or forfeit our opportunity to be leaders in this area.
References:
Daniell, H. (2002) Molecular strategies for gene containment in transgenic crops. Nat. Biotechnol. 20:581-586.
Felsot, A. S. (2002) Pharm Farming: It's not your Father's Agriculture. Agrichemical and Environmental News, Issue No. 195 (See http://aenews.wsu.edu).
Jemison, J. M. and Vayda, M. E. (2002) Cross Pollination From Genetically Engineered Corn: Wind Transport And Seed Source. AgBioForum, Vol. 4, Article 2. (See http://www.agbioforum.org/v4n2/v4n2a02-jemison.htm).
Purseglove, J.W. (1972) Tropical crops (Chapter 1 - monocotyledons) London: Longman group.
Stevens, W., Berberich, S., Wiltse, C., Horak, M., Halsey, M., Remund, A., Sheckel, A. and Dunn, D. (2002) Gene flow studies to optimize containment of regulated products produced in corn. Paper presented to the American Society of Agronomy.