American Journal of Law & Medicine

Consuming (f)ears of corn: public health and biopharming.

I'm convinced that physical containment is overrated and, while reassuring to the psyche, is hardly the line of defense one would like to put the greatest reliance upon. (1)

So what you have to keep asking yourself is: Suppose the worst happens, what are the consequences? (2)


We have entered the biotech century. Advances in biotechnology (3) are already transforming medicine, agriculture, and industry in ways undreamt of thirty years ago, and the pace of scientific advances can only be expected to accelerate. Just as the industrial revolution completely transformed the era of craft and guild production, the world that biotechnology produces may be all but unrecognizable from today's vantage point. (4)

One of the most controversial and exciting prospects of biotechnology is biopharming--a process in which plants are genetically modified so that they endogenously produce specialty pharmaceutical or industrial proteins. (5) Many such crops are currently being planted in small test plots throughout the country. (6) Once they are fully developed and approved, these biopharm crops will be grown in the same agricultural fields that are currently devoted to producing traditional agricultural crops. (7)

Biopharm companies envision a lucrative future in which agricultural fields, converted into biofactories, grow the raw materials for industrial or pharmaceutical production. Among the dazzling possibilities are plants that produce specialty industrial compounds like biodegradable plastics (8) and polyesters; (9) or drugs to treat a variety of human diseases, such as cancer, HIV, and Alzheimer's. (10) The allure of these crops is clear--an environmentally sustainable (11) and inexpensive replacement for costly drugs and petrochemicals. (12)

At the same time, there are some jarring points of tension, if not outright contradiction, between widespread planting of biopharm crops and the ongoing expectation of a safe and secure food supply. (13) Biopharming frequently uses corn and other food crops as production vehicles, but these crops are emphatically not food and are not intended for human consumption. (14) Biopharm crops, therefore, pose "a wholly different order" of environmental and human health risks. (15) Despite the unique risks, biopharm crops have been tested in fields across the country under the same laissez-faire standards used for first-generation genetically modified ("GM") crops--with minimal and poorly enforced safety precautions based on physical containment. (16) In the last decade, biotech companies and research universities have violated even those minimal safety precautions more than a hundred times. (17) Because many of these open-air field tests of experimental biopharm crops take place in the Corn Belt, these violations put the food supply at a high risk for contamination. (18)

Contamination of food crops with non-food, biopharm compounds is a serious threat to human safety and could result in rapid dissemination of non-food pharmaceutical or industrial compounds through the world food supply. There is no room for trial and error. Once contamination occurs, it will be next to impossible to reverse this process and "uncontaminate" the food supply. (19) Unfortunately, important safety issues have been sidelined in order to facilitate rapid growth of this nascent industry. First and foremost, readily available and far safer alternatives could be used instead of food crops for biopharm production. But, because market forces diverge from the public's interest on this point, those safer options have not been pursued. Without government action forcing innovation towards achieving public health ends, it is clear that these options will remain unexplored. At the very least, there should be a moratorium on field testing these crops until a host of health-related questions are answered. Among the most pressing questions are: Do biopharm residues bioaccumulate? (20) Is there a threshold below which these compounds can be safely consumed? Are there low-level, long-term health effects? Are these compounds allergens (21) or toxins? (22) Are biopharmed crops anti-nutrients? (23) How persistent are these compounds in the soil? How toxic are they to wildlife? How likely is the prospect that these non-food compounds could be spread to wild relatives? (24)

Unfortunately, under the U.S. fractured regulatory system, there is no way to pose these questions with regard to biopharm crops, let alone to answer them. Part of the problem is that no regulatory agency has a clear statutory mandate to regulate biopharming. (25) As a result, there are no coherent overarching government policies capable of ensuring that this new technology is safely explored and exploited. (26)

The crisis is on our doorstep. According to some predictions, at least 10% of U.S. agricultural lands will be devoted to biopharming by the end of the decade. (27) Thousands of inedible and potentially harmful compounds may soon be grown in corn fields throughout the country. Without detailed and enforceable standards for responsible use of this new technology, it is inevitable that these biopharm crops will contaminate crops destined for use as human food. (28) The health risks from consuming these adulterated foods could be considerable.

Nevertheless, industry and governmental regulators have failed to impose obvious biological controls that would greatly protect the public's safety, while still permitting exploitation of this technology. For example, biopharming ought not be done in food crops, or, at the very least, ought not be released into the open environment of an agricultural field (as opposed to being grown in a greenhouse) before basic research has demonstrated that there will be no negative health effects from consuming contaminated foods. (29) Instead of adopting these sensible precautions, regulators have simply assumed that contamination can be avoided through use of physical containment measures. This wildly optimistic assumption is not shared by biopharm developers who admit that biopharm proteins will likely wind up in the food supply. Moreover, physical containment measures have not shown much success in existing GM crops. (30)

The limited scope of existing biopharm regulation leaves the public unprotected and exposed to an unacceptable level of risk. Moreover, the mere threat of commingling may be enough to destroy the United States' multi-billion dollar export trade in corn and other commodities. (31) These failures to address the problem of contamination and commingling become even more critical now that the Cartagena Protocol on Biosafety has entered into force. (32) Article 10 of the Protocol gives states the power to refuse import of the products of biotechnology (called living modified organisms or LMOs in the Protocol) in order to avoid or minimize adverse effects on human health or the conservation and sustainable use of biological diversity. (33) It is hard to imagine anything more likely to justify a refusal to import under the Cartagena Protocol than undetectable commingling of industrial or pharmaceutical crops containing non-food proteins with export food crops. Protecting the public's interest in this context will require government to assume a far more active role than the hands-off attitude that has been the hallmark of conventional agricultural policy.

This Article raises a few of the more pressing public health questions that should be resolved before substantial portions of the nation's crop land are diverted from food production to biopharming. Part II provides an introduction to biopharming and outlines the various plans and projections for its commercial exploitation. Part III examines the existing regulatory structure, highlights some of its most critical weaknesses, and points out the serious risks this structure creates vis-a-vis the integrity of the food supply. Part IV articulates a central conclusion that safe and successful exploitation of these new technologies will demand a markedly different regulatory regime than the laissez-faire system that has prevailed in conventional agricultural policy. To that end, the final Part proposes some alternatives that would better safeguard public health while still permitting exploration of this exciting new technology.


Over centuries and millennia, humans have domesticated modified food crops in order to improve their agronomic and nutritional characteristics. For most of human agronomic history, this was a process of trial and error. Although it was clear that desirable agronomic traits could be inherited, there was no way to predict the outcome of a cross between any two particular plants. In 1865, an Augustinian monk named Gregor Mendel changed all that. Working with pea plants, Mendel deduced that offspring inherited traits from their parents in predictable patterns. His paper, Versuche uber Pflanzen-Hybriden ("Experiments in Plant Hybridization"), (34) concluded that "heritable factors" (genes or alleles) come in pairs; segregate independently; and are governed by principles of dominance and recessiveness. Although the paper initially went unnoticed in scientific circles, these patterns of inheritance are now referred to as the Mendelian laws of genetics.

Armed with an understanding of Mendel's work, plant and animal breeders transformed agriculture. By systematically crossing and recrossing individuals with desirable characteristics, breeders were able to create new varieties that were more productive and easier to grow. (35)

Almost a century later, James Watson and Francis Crick's 1953 paper, A Structure for Deoxyribonucleic Acids, described the structure of DNA--the molecule responsible for Mendelian inheritance. (36) This paper is generally considered to have ushered in the era of molecular genetics. (37) The discovery of the chemical structure of DNA opened up new vistas in biological and biochemical research. (38)

By the early 1970's, Stanley Cohen and Hubert Boyer had built on Watson and Crick's work by successfully splicing a gene from one organism and moving it into another--the first use of recombinant DNA technology. (39) Suddenly researchers could move genes from one species to another, thus overcoming the reproductive limits imposed by sexual incompatibility among species. (40) Recognizing the perils potentially associated with their new technique, Cohen and Boyer attempted to exercise some control over its uses. (41)

Cohen and Boyer's concerns about the potential hazards of these new techniques mirrored similar concerns that other researchers were expressing. (42) In light of the as-yet-unassessed, but potentially harmful, consequences of this new research, the scientific community called for a voluntary moratorium on genetic engineering. (43) At a 1975 conference held at Asilomar Conference Center in Pine Grove, California, 150 scientists from around the world met to hammer out a set of safety precautions for genetic research. (44) Known as the Asilomar Consensus Statement, the conference recommended lifting the self-imposed moratorium and replacing it with guidelines for genetic engineering research. (45) The central assumption behind the consensus statement was that the unknown hazards of genetic engineering should be contained biologically and physically. (46) This consensus formed the basis for the Recombinant DNA Research Guidelines issued by the National Institutes of Health ("NIH") in 1976. (47)

Until 1984, these guidelines, which applied to researchers funded by NIH, governed approval of DNA research. A successful legal challenge to decisions made under those guidelines forced the Reagan Administration to develop a more overarching regulatory policy to guide federal decision-making about biotechnology research and its products. (48) To that end, the Office of Science and Technology Policy issued the Coordinated Framework for Regulation of Biotechnology. (49) The Framework purported to describe the comprehensive federal regulatory policy for ensuring the safety of biotechnology research and products. (50) The Framework announced that no new laws would be needed to respond to challenges posed by this new technology. (51) Instead, products of biotechnology would be regulated under existing laws based on their intended use; thus, food would be regulated under the Federal Food, Drug, and Cosmetic Act, (52) pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act, (53) agricultural plants under the Plant Protection Act, (54) and so on. (55) One unfortunate consequence of this reliance on existing law has been an erosion, over time, of the commitment to biological containment measures.

During the 1980s, researchers developed bioengineering methods to integrate foreign DNA permanently into plant genomes, enabling the production of transgenic plants expressing a wide variety of foreign genes. (56) In a process called transformation, (57) genes coding for a specific trait can be isolated from any organism and inserted into the embryos of any food crop. (58) The transformed embryos are then grown into adult plants that express the newly added trait. Through bioengineering, researchers have been able to manipulate plants in unprecedented fashions and to sequence a series of plant genomes. (59) Information gleaned from this new technology opened up immense possibilities for agriculture and began the rapid cascade of scientific progress that I call "the ag-biotech revolution."

The first bioengineered, or GM crops were commercialized in 1996. By 2001 U.S. farmers were devoting approximately 88 million acres to GM crops (60)--the lion's share of the 130 million GM acres planted worldwide. (61) In 2003, 73% of the cotton, 81% of the soybeans, and 40% of the corn planted in the United States were GM varieties. (62) Biotech research has grown at an even more explosive rate. In 1994, approximately 7,000 acres in the United States were planted with 593 biotech field tests; in 2001, there were 57,000 experimental acres planted with 1,117 field tests. (63) While most of these were field tests of first-generation GM crops (those engineered for herbicide resistance or to produce endogenous pesticides), some 300 were biopharm crops. (64)


During the 1990s, researchers around the world embarked on the most ambitious biotechnology project ever--the sequencing of the human genome. (65) The Human Genome Project (66) and related biomedical research spawned a generation of highly specialized drugs based on antigens (vaccines), recombinant proteins (biologics) and human antibodies (collectively "therapeutics"). (67) Demand for therapeutics is growing rapidly, especially those designed for chronic illnesses like psoriasis, allergic asthma, and rheumatoid arthritis. (68) Meeting the projected demand for these therapeutics will require thousands of kilograms of purified proteins. (69)

Commercial production of these products currently relies on abiotic fermentation (primarily in E. coli or yeast) or on mammalian cell culture (primarily in Chinese hamster ovary cells ("CHO cells")). (70) These expression systems have some serious drawbacks: they tend to be expensive, labor intensive, and they produce relatively low yields that fall short of supplying all patients in need. Generally, recombinant mammalian systems can produce about 1-4 grams of a therapeutic protein per liter of media every 2-3 weeks, (71) while recombinant E. coli systems yield 1-4 grams per liter every 1-2 days. (72) Recombinant monoclonal antibody culture in CHO cells yields .5-1 gram per liter per day, and mammalian cell perfusion bioreactor systems yield about .3 gram per liter each day. (73) Biopharming represents the cutting edge of the research on increasing yields with at least 120 different research institutions currently developing a staggering array of biopharm products. (74)

At least in theory, plants can be engineered to express high levels of the desired pharmaceutical protein. (75) One 200-acre biopharm field could therefore produce significantly greater quantities of therapeutics than current methods. Moreover, biopharm crops offer some other distinct advantages for producing pharmaceutical proteins. Large-scale biopharming of these compounds should be more economical than current production techniques that rely on mammalian cell cultures. Because biopharming can be done by ordinary farmers in ordinary fields, rather than by highly skilled workers in high-tech facilities, the capital investment costs are relatively low. (76) Some estimates indicate that biopharming could reduce production costs for these therapeutics by an order of magnitude. (77) Biopharming can also draw on a wealth of existing agronomic experience with growing, harvesting and processing these crops in their conventional forms. Unlike CHO cell or E. coli production techniques, biopharming does not require a highly educated and tech-savvy workforce. Biopharmed therapeutics may also be safer than those produced via existing techniques, because plant-produced therapeutics have a reduced risk of carrying human pathogens. (78)

The range of possible biopharm products under development is truly staggering. (79) For example, researchers at the Washington State University have transformed barley so that it produces [[alpha].sub.1]-antitrypsin, a human blood plasma protein used to treat cystic fibrosis and various skin diseases. (80) Barley has also been transformed to produce Antithrombin III, a human anticoagulant. (81) There has been a great deal of research on antibody production in biopharm plants, so-called "plantibodies," (82) and various research teams have demonstrated the possibilities of growing biovaccines against infectious diseases like cholera, (83) hepatitis B, (84) Norwalk virus, (85) and traveler's diarrhea. (86) Pre-clinical trials for these biovaccines have demonstrated that plant-grown vaccines can be effective in humans. (87) Researchers at ProdiGene and Epicyte have transformed corn to produce human monoclonal antibodies to treat HIV, (88) and herpes simplex, (89) and a team at Cornell has developed individualized biovaccines to treat non-Hodgkin's lymphoma. (90) ProdiGene currently biopharms avidin corn for use as a research grade chemical, (91) and Epicyte has developed a corn-grown spermicidal plantibody that it hopes to market as a contraceptive. (92)

Although biopharm research has been conducted on a wide variety of plant species, corn has become the crop of choice for biopharm companies looking to commercialize their products. (93) Indeed, the number of corn field tests dwarfs experimentation in all other crops combined. (94) Corn does offer a number of advantages--particularly the utility of corn cobs as a pre-packaged, cheap, and easily transported storage system. Unfortunately, this use of corn raises some serious safety questions because of the likelihood of contaminating the food supply. Corn is, after all, a promiscuously outcrossing, wind-pollinated plant. (95) Although companies routinely claim that test site locations are confidential business information ("CBI"), (96) rendering that information unavailable to the public, much of this testing apparently occurred in the Corn Belt. (97)


Biopharming is an integral part of President Bush's energy policy and associated initiatives and was strongly supported by President Clinton before him. (98) In 2000, Congress passed the Biomass Research and Development Act, (99) which created an interagency Biomass Research and Development Board and a Biomass Research and Development Technical Advisory Committee. (100) In 2002, the Advisory Committee published a National Vision Statement and a Biomass Roadmap for bioenergy and biobased products. (101) The Vision Statement sets a goal of satisfying 18% of the 2010 production target of chemical commodities through biobased production. (102) One of the articulated, and oft-repeated goals of the Vision Statement and its accompanying Roadmap was "remov[al of] the barriers facing biomass technologies." (103) The Committee's charge extends to all biobased industries, including biopharming. (104)

Although this Committee was a joint project between the Departments of Energy and Agriculture, the Vision Statement and Biomass Roadmap were emphatically a product of the interested industries. Perhaps not surprisingly, the tenor of the Committee's public policy recommendations was to support and facilitate development of biobased industry and to downplay any drawbacks. …

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