Technological Forecasting & Social Change 72 (2005) 521–534

Trends affecting the next generation of U.S. agricultural

biotechnology: Politics, policy, and plant-made pharmaceuticals

Patrick A. Stewarta,*, Andrew J. Knightb

aDepartment of Political Science, Masters of Public Administration Program, P.O. Box 1750, Arkansas State University,

State University, AR 72467, USAbDepartment of Criminology, Sociology and Geography, Arkansas State University, State University, AR 72467, USA

Received 7 December 2003; received in revised form 3 March 2004; accepted 4 March 2004

Abstract

This paper analyzes the structure and history of regulatory policies in the United States, focusing on recent

regulatory changes due to the promise and threat posed by plant-made pharmaceuticals (PMPs). PMPs are the

latest advance in the genetic engineering of plants and promise to produce medicines inexpensively and abundantly

by using a range of different plants as factories to express active medicinal ingredients; however, PMPs may pose a

risk to the public’s health if they enter the food supply. How the benefits and risks of PMPs are addressed by the

respective government’s regulation and how this will affect what, if any, products make it to the marketplace and

their ultimate success are of great concern to many different parties, ranging from consumers and farmers to health

and food production industries. As a result, this paper addresses the history of agricultural biotechnology

regulatory policy since 1972, arguing that three distinct periods may be identified: (1) from 1972 to 1986 when the

new biotechnology was focused on scientific self-regulation in the laboratory; (2) from 1987 to 2002, as the

technology was being developed and widespread release of certain technologies became more common and was

not perceived as an environmental threat, regulations became increasingly laxer; and finally, (3) we argue that we

are entering a third phase with a series of controversies over regulatory infractions involving genetically

engineered (GE) plants and the potential threats posed by PMPs.

D 2004 Elsevier Inc. All rights reserved.

Keywords: Genetic engineering; Agricultural biotechnology; Regulation; Field releases; Plant made pharmaceuticals, PMPs;

Plant-made industrial products, PMIPs

0040-1625/$ - see front matter D 2004 Elsevier Inc. All rights reserved.

doi:10.1016/j.techfore.2004.03.001

* Corresponding author.

E-mail address: pstewart@astate.edu (P.A. Stewart).

P.A. Stewart, A.J. Knight / Technological Forecasting & Social Change 72 (2005) 521–534522

1. The next generation in U.S. agricultural biotechnology

While genetically engineered (GE) crops, such as Round-Up Ready soybean and Bacillus thur-

ingiensis (Bt) corn and cotton, have become a pervasive part of agricultural production in the United

States over the past 7 years, their place in the market is by no means assured. International trade concerns

and recent crises played out in front of the public have the potential to not only stifle support for these

products, but also lead to their being discarded if they are perceived by producers and retailers as too

much of a risk. With many nations following the lead of Europe by not accepting goods derived from GE

plants into their markets, or demanding their labeling, consumers will not have an opportunity to

purchase these products, as these markets will remain closed. In countries that are willing to embrace

genetic engineering plants, like the United States, if consumers are unwilling to buy these products and

the public is unwilling to accept the risk of GE plants being grown, it is unlikely that GE crops will

survive as part of the agricultural system. Public opinion is often the key driver in regulatory change. As

a reaction to public perception of potential threats and not experienced events, the biotechnology

regulatory arena has experienced a good deal of change since 1986. Because of the lack of substantive

experience with health and/or environmental threats from the release of biotech products, federal

government agencies established an amalgam of existing regulations to respond to potential, but not

established, threats. These regulations use genetic engineering as the trigger and have undergone a series

of alterations, as more knowledge of the risks associated with the release of GE plants has been

accumulated, as well as in response to public reactions, or lack thereof, to perceived risks.

Likewise, change in the field testing of plant biotechnology has occurred since the regulatory regime

was put in place in 1986 and field releases began in 1987. Three different generations of alterations to

plants have been identified as likely taking place. First-generation biotechnologies alter the character-

istics of plants so that they require less agricultural inputs such as herbicides, pesticides, and fertilizer as

well as other chemicals. Second-generation biotechnologies focus on improving product quality so the

plants are more nutritious, tastier, or stay fresh longer. Third-generation GE plants are ones in which cash

crops act as ‘‘factories’’, producing industrial goods, pharmaceuticals, and other products more

efficiently and cheaper than traditional approaches [1].

First-generation products, such as Round-Up Ready herbicide tolerant plants and Bt insecticidal

crops, are used extensively by farmers. While crops exhibiting product quality characteristics have been

given regulatory approval, the second-generation crops have yet to catch on in the marketplace. For

instance, Calgene’s Flavr Savr tomato, which was designed to have a longer shelf life and a better taste

than traditional tomatoes, appeared briefly in grocery stores but was eventually pulled from the shelves

due to marketing and transportation problems.

Finally, the third generation of GE crops includes plant-made pharmaceuticals (PMPs) and plant-made

industrial products (PMIPs). PMPs are designed to produce vaccines and antibodies for a wide range of

diseases like rabies, traveler’s diarrhea, cholera, hepatitis B, antibodies to fight cancer, and tooth decay,

and therapeutic proteins for cystic fibrosis, liver disease, and hemorrhages. PMIPs can be used for a

variety of industrial purposes, such as to accumulate heavy metals in the plant to clean up soil, perform

as biosensors for hazardous materials such as explosives found in landmines, produce enzymes and

epoxies for industrial uses and plastics to replace petroleum-based products, and to produce cosmetics

[2]. GE plants, however, have not been embraced by all segments of society, as criticism and controversy

have attended their production, particularly as issues surrounding environmental and health risks have

become publicized.

P.A. Stewart, A.J. Knight / Technological Forecasting & Social Change 72 (2005) 521–534 523

This paper considers the future of new agricultural biotechnology applications, particularly third-

generation products such as PMPs and PMIPs, by analyzing the regulations that allow these products to

be field-released and marketed. This paper will first examine the regulatory history of new agricultural

biotechnology products by analyzing the events that led to the promulgation of regulations and whether

the events led to more stringent or relaxed regulations. Next, the paper will consider trends in the new

agricultural biotechnology development by analyzing the U.S. Department of Agriculture (USDA)

Animal and Plant Health Inspection System’s databases. Specifically, we analyze trends in field releases

considering the types of plants that are being genetically engineered and the types of interventions being

considered. We conclude by considering the future of the new agricultural biotechnology applications in

light of trends in regulation, field experimentation, and politics.

2. Regulatory change and prevailing sentiment

The regulation of agricultural biotechnology can be seen as having been sequestered in a fairly well

insulated policy subsystem, with little public involvement due most likely to its highly technical nature.

As a result, there was little need for institutional intervention by Congress, the Executive Branch, or the

Judicial Branch [3]. More recently, forces within the policy subsystem have led to the relaxation of

regulations through the promise of new products and dearth of experienced difficulties in the field

experiments. However, recent focusing events, such as the GE corn’s effects on the monarch butterfly,

GE animal feed entering the United State’s food supply, and a plant pharmaceutical nearly entering the

food supply, have publicized and politicized agricultural biotechnology and the regulatory arena, leading

to greater scrutiny by more parties and stricter regulations [4].

When looking at the regulatory history of new agricultural biotechnology applications since 1972, a

pattern seems to emerge, with three different identifiable periods. The first time period can be considered

to start with the impetus to self-regulate by the scientific community, beginning with the Asilomar

Conference Center and ending with formal government regulation of field releases, with the promul-

gation of the Coordinated Framework by the Executive Branch’s Office of Science and Technology

Policy (OSTP). The second time period extended from the Coordinated Framework until recently, with

the widespread release of the new products of agricultural biotechnology in the fields, especially Bt corn

and cotton, and Round-Up Ready soybean. This period is marked by a deregulatory trend, as regulations

concerning the field release of GE plants were progressively relaxed. The third time period, the one into

which we are currently entering, marks a return to scientific concern and regulatory restriction, as a

series of events have called into question the safety of GE crops. These events have spurred a systematic

questioning of the regulation of GE plants in general, and PMPs and PMIPs specifically.

2.1. In the lab: Asilomar (1972) to Coordinated Framework (1986)

The impetus for regulation of the new biotechnology came not from an experienced catastrophe or

crisis, but from public concerns about potential environmental disaster. Well-meaning, but politically

inexperienced, scientists called for self-regulation to address public concerns they inadvertently kindled.

Specifically, in 1974, a meeting called for by a group of eminent scientists in one of the most visible and

important journals in the scientific world (Science) was attended by 150 carefully selected participants at

the Asilomar Center in Pacific Grove, CA [5]. This meeting, which was held to calm public concerns

P.A. Stewart, A.J. Knight / Technological Forecasting & Social Change 72 (2005) 521–534524

over the use of recombinant DNA technology, instead highlighted the uncertainty of elite scientists and

their desire to restrict debate to within the scientific community by limiting public involvement and press

coverage [6,7]. While the result, scientific self-regulation with restraints only enforced on Federally

funded projects [specifically, by the National Institutes of Health (NIH)], was as intended, the Asilomar

conference and the events attending it served to set in motion a risk-averse perspective in which the

threat of the new biotechnology was assumed before it was proved. This in turn led to it being the first

technology to be regulated before risk was shown to exist ([8,9] p.223).

Over the next decade, most research tended to be laboratory-based. However, as the new

biotechnology started moving from the lab to the field, concerns over field releases of GE organisms

were raised, especially by such interest groups as the Foundation on Economic Trends (FET). One GE

organism in particular raised concern—a soil bacterium genetically altered to reduce the likelihood of

frost damage by lowering the point at which ice forms on a plant, in turn preventing an estimated US$1

billion in losses annually. Unfortunately dubbed ‘‘ice-minus’’, the perceived threat of the bacterium

escaping, proliferating, and altering the environment was used as a focusing event to draw attention to

the potential dangers raised by the new biotechnology, especially as the FET brought suit against the

Environmental Protection Agency (EPA) for not protecting the environment against this threat.

This, combined with the need to clarify administrative turf who had regulatory primacy over the

nascent industry and broader environmental concerns, led to the Reagan Administration’s OSTP

proposing the Coordinated Framework for the Regulation of Biotechnology (hereafter the Coordinated

Framework) in 1985, and its being promulgated in 1986 ([6] p. 192–197). The resultant Coordinated

Framework coordinated the regulatory jurisdictions of the Food and Drug Administration (FDA), NIH,

EPA, USDA, and the National Science Foundation (NSF). In all cases, a ‘‘pragmatic’’ approach was

used in which preexisting regulations were utilized on a product-by-product basis, but with the use of

genetic engineering processes to set off the regulatory trigger ([10] p. 79). The Coordinated Framework

put in place dealt with jurisdictional overlap between the USDA, EPA, and FDA1 with GE plant

products as they move from the field to consumers.

The first line of regulatory oversight with the field release of GE organisms was and remains the

USDA’s Animal and Plant Health Inspection Service (APHIS), primarily through the Plant Quarantine

Act (PQA) and the Federal Plant Pest Act (FPPA), although USDA also claims oversight through the

Federal Meat Inspection Act (FMIA), the Poultry Products Inspection Act (PPIA), the Virus, Serum,

Toxin, and Analogous Products Act (VSTA), and the Federal Seed Act (FSA). The EPA’s regulatory

oversight comes into play when products reach the commercial stage of development through the

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Toxic Substances Control Act

(TSCA). Finally, FDA regulates the new biotechnology under the Federal Food, Drug and Cosmetic Act

(FFDCA) and the Food Quality Protection Act (FQPA), which also affects EPA to a lesser extent.

2.2. In the fields: Coordinated Framework (1987) to widespread field release (2002)

As previously stated, the initial point where GE organisms are regulated is by the USDA as field

releases, or the movement of GE organisms into or through the United States, under 7 CFR part 340 of

the FPPA and the PQA. Under these acts, APHIS asserts broad regulatory authority over organisms,

products, and articles that are plant pests or could harbor plant pests, whether they are genetically

1 Until relatively recently, FDA has regulated GE plants as substantially equivalent.

P.A. Stewart, A.J. Knight / Technological Forecasting & Social Change 72 (2005) 521–534 525

engineered or not. Although the Coordinated Framework explicitly states federal agencies should focus

on characteristics of risk posed by the product, APHIS uses genetic engineering to trigger regulatory

oversight. With the permitting process, which was established in 1987 to allow for field testing of GE

plants, the process applies to organisms using genetic materials from organisms defined as plant pests,

unknown or unclassified organisms, or organisms that the APHIS deputy administrator determines to be

or has reason to believe is a plant pest [11].

These regulations, however, are not encompassing of all GE plants. While the use of recombinant

DNA inserted through Agrobacterium is a trigger for regulation, recombinant DNA inserted through a

gene gun, genes inserted that do not come from a listed plant pest, or a plant whose pest status is

undetermined do not trigger the same regulations. Although creators of such plants have, to date, sent

courtesy notifications or permit applications ([12,13] p. 107), there is no certainty that this practice will

continue.

In March 1993, the permitting process was changed by APHIS to include a notification track in order

to simplify the process. Six plant species, corn, cotton, potato, soybean, tobacco, and tomato, which were

considered genetically well characterized, and in which the transmission of GE characteristics were seen

as limited due to the lack of wild relatives in North America, were given notification status. The

reduction of paperwork through the use of the notification track, instead of the permitting procedure, led

to a decrease in the average waiting period from 120 to 30 days, and costs from US$5000 to US$250

dollars. As can be expected, there was a sudden upturn in field release activity, especially regarding these

crops (see Fig. 1).

In May 1997, further changes to the field release regulations were put in place by APHIS to allow the

introduction of the great majority of GE plants under the notification procedure. With this approach, a

plant is eligible for the notification process if it meets the following requirements: the plant species is not

listed as a noxious weed in the area where it is to be released; the inserted DNA is stably integrated into

the host genome; the inserted DNA’s function is known and does not cause production of an infectious

Fig. 1. USDA-APHIS field releases.

P.A. Stewart, A.J. Knight / Technological Forecasting & Social Change 72 (2005) 521–534526

entity; encoded substances are not toxic to nontarget species likely to feed on the plant or encode

products for pharmaceutical use; virus derived sequences must be unlikely to facilitate virulence and

spread in plants; and, finally, the new genes must not be derived from human- or animal-disease-causing

agents ([13] (p. 109–109); [11]). In other words, unless there is seen to be an environmental threat from

the new plants, the less rigorous data collection standards of the notification approach is applied. As can

be seen in Fig. 1, this led to an increase in use of the notification track as well as a decrease in utilization

of the permitting track.

Statistical analysis supports the contention that policy changes put in place since 1987 have led to

greater field release activity. Regression analysis of the effect of policy change on total field release

activity over 15 years, measured as permits plus notifications, suggests this, as the model is highly

significant and explains a good proportion of the variance (adjusted R2=0.955), while not showing

autocorrelation (Durbin–Watson = 2.070). Analysis of the parameter coefficients suggests that all

variables are significant at the 0.10 level and have a positive effect. Specifically, the year variable is

highly significant and shows an increase in, on average, 52 field releases a year since the APHIS

program was put in place. The two regulatory changes also had a significant, though lesser, effect on the

amount of field releases with the 1993 policy change accounting for an additional 229 field releases per

year and the 1997 policy change leading to an added 190 field releases a year (Table 1).

Further analysis of trends in field release through consideration of the utilization of the permitting

track bolsters the contention of the notification track replacing the permitting approach. While the model,

which incorporates both regulatory changes, does not meet model statistics, removing the effect of the

first regulatory policy change in 1993 leads to the model reaching statistical significance at the 0.10

level, although it only explains a fraction of what can be expected of a time series regression analysis and

there is suggestion of autocorrelation, meaning the model does not have the correct variables for

specification. However, what can be gleaned from the model is an increase of about eight permits a year.

The change to regulatory policy in 1997 led to a decrease in permitting activity by an order of about 96 a

year, suggesting that other factors are at work.

Finally, the 1993 APHIS policy change put in place a petition process that allowed for the

determination that certain plants are no longer regulated articles. Furthermore, an extension process,

whereby closely related plants are ascribed a nonregulated status, was put in place ([13] p. 104). Once it

has been decided by APHIS that a transgenic plant has nonregulated status, APHIS cannot exercise

Table 1

Field releases of genetically engineered plants

Total field tests Permits model #1 Permits model #2

Intercept � 104,290.9 (29,423.84)*** � 16,280.44 (12990.17) � 15,649.19 (7902.63)*

Year 52.45 (14.79)*** 8.213 (6.529) 7.90 (3.97)*

Policy change 1 (1993) 229.17 (95.47)** � 2.646 (42.15)

Policy change 2 (1997) 190.17 (95.47)* � 97.146 (42.15)** � 96.19 (37.79)**

Adj. R2 0.955 0.169 0.233

F-test 106.05*** 2.02 3.279*

Durbin-Watson 2.070 1.242 1.247

* Significant at 0.10.

** Significant at 0.05.

*** Significant at 0.01.

P.A. Stewart, A.J. Knight / Technological Forecasting & Social Change 72 (2005) 521–534 527

additional oversight over the plant and its descendants, even if separate deregulated lines are crossbred

conventionally. This might lead to wild species with potential weediness problems ([13] p. 111–112).

Change during the period from 1986 to 2002 can be effectively seen as occurring within the

agricultural biotechnology subsystem with minimal public input. Specifically, changes in 1992 and 1997

to USDA-APHIS field release regulations, while spurred by OSTP directives, did not incorporate public

input to any great extent. The lack of negative events, along with increased knowledge and experience

with rapidly advancing and diversifying GE plant field testing, precipitated the easing of regulations.

Furthermore, the lack of public input and likely recalcitrance to allow deregulated field experimentation

of an uncertain technology certainly accelerated this trend towards relaxed regulations.

2.3. In the public eye: on the precipice of changes to the regulatory framework 2002—??

The most recent changes to the regulatory structure concerning agricultural biotechnology are coming

about, due in great part to concerns ‘‘that the expansion in agricultural biotechnology increasingly will

put pressure on seed production and commodity handling systems’’ ([14] p. 50578) to segregate and

control its products. Further, the concomitant diversification of GE plants with agronomic properties,

consumption traits, and industrial production qualities that may enter into the environment have stirred

doubts as to their safety. Specifically, concerns over the current regulatory scheme, with its relatively

insulated policy-making approach, have been raised by three separate events at the turn of the century

that have called into question the scientific basis for regulation, the effectiveness of regulatory

enforcement, and the integrity of the food system.2

The first of these focusing events occurred in 1999 when a laboratory study published by Losey et al.

(1999) [15] in the eminent peer-reviewed scientific journal Nature called into question the environmental

safety of Bt, which was engineered to express a protein that kills targeted insects that attack

economically important crops such as corn, cotton, and potato by eating through their guts, leading

to sepsis and the inability to digest food. This article suggested that the monarch butterfly, a highly

visible symbol of the environment, as well as other beneficial insects, would be harmed by Bt corn

pollen while in their larva stage. While technically correct and seen by those in the industry as acceptable

collateral damage due to its having a negligible effect on these butterflies, this study led to a debate and

follow-up studies that lasted for over 2 years and drew a good deal of media coverage ([16] p. 189–192).

Additionally, it pointed out potential flaws in the Coordinated Framework, as the effect of pollen

that expressed Bt was not considered until after Bt corn was in the field. Specifically, the Bt corn in

question moved through the APHIS field release regulatory process, which only considers the

likelihood that a plant will become a plant pest and only indirectly considered potential harms to

nontarget species, without consideration of potential harms to such species as monarch butterflies.

EPA regulations, inasmuch as they deal with plant-incorporated protectants (PIPs)3 such as Bt crops

2 It is not the case that other compliance infractions have not occurred. USDA states that of the 7402 field tests carried out

between 1990 and 2001 and regulated by APHIS, 115 resulted in compliance infractions [22]. For the most part, however, these

were relatively minor infractions and did not raise public concern. Of potentially greater long-term concern were infractions

concerning EPA regulations over the management of Bt corn, in which large numbers of farmers have not been following

standards [24]. The nature of the technology and the form of EPA’s regulatory authority, however, make it difficult to observe

and punish individual infractions [26], and thus, these infractions have likewise not been of public concern.3 The term PIPs (plant incorporated protectants) reflects a desire by industry to avoid the more accurate, yet more

inflammatory term ‘‘plant pesticides’’ previously used by EPA to refer to plants with engineered pesticidal qualities.

P.A. Stewart, A.J. Knight / Technological Forecasting & Social Change 72 (2005) 521–534528

under FIFRA, does have regulatory authority if the pesticidal substance (the crops with PIPs) harms

nontarget species. While regulatory action was not taken, the result was that by the 2001 field season,

Ciba Seeds (Novartis), the company producing the type of Bt corn most toxic to the monarch

butterfly, removed that particular Bt corn from the market in spite of it being ‘‘a significant market

force during 1996–1999’’ ([13] p. 72–75).

The second controversy garnering national attention and concern likewise dealt with Bt corn. Avariant

of Bt, which is expressed in Starlink corn and not deemed fit for human consumption due to potential

human allergic reactions but seen as safe for use as animal feed, found its way into the human food supply.

The public interest group ‘‘Genetically Engineered Foods Alert’’ performed tests on taco shells and other

corn-based products being sold in grocery stores, like Safeway, and in fast food restaurants, such as Taco

Bell, and found that these products contained Starlink Bt corn [16]. Indeed, within a single year, of

110,000 grain tests by Federal inspectors, Starlink corn showed up in one tenth [1].

The resulting uproar led to actions by EPA to cancel the registration of this corn in spite of Starlink’s

parent company Aventis attempting to win approval based on its safety as Generally Recognizable As

Safe (GRAS) from FDA. However, when this was discarded as an option, Aventis and USDA bought

back existing grain supplies and recalled food with Starlink corn in it. Further, EPA no longer allows

‘‘split’’ registrations in which PIPs may be registered for animal feed but not for human consumption. As

a result of this, public attention was drawn to flaws in the regulatory system, especially the ease in which

food security may be breached, and Congressional hearings were held to discuss this and other concerns

with agricultural biotechnology [16].

The final focusing event, that of Prodigene’s PMP corn, has likewise led to public concern over the

safety of the food supply. In September and October of 2002, in Iowa and Nebraska, respectively,

APHIS found ‘‘volunteer’’ corn plants genetically engineered to produce a pharmaceutical to prevent

‘‘traveler’s diarrhea’’ growing in soybean fields in violation of permit conditions. Specifically, Prodigene

did not abide by the conditions of their field release of PMPs from the previous year as small quantities

of this corn ended up in soybean that was to be processed and sold for human consumption. As a result

of this, Prodigene had to pay a civil penalty of US$250,000, destroy 500,000 bushels or $2.7 million

dollars worth of soybean in Nebraska, and incinerate 155 acres of corn in Iowa due to concern that cross-

pollination occurred, as well as post a US$1-million-dollar bond and accede to higher compliance

standards for future field tests [17]. Further, and perhaps more important in terms of long-term political

implications, the Grocery Manufacturers of America (GMA) and other food processing interest groups

expressed concern over plant made pharmaceutical field test regulations, with John R. Cady, CEO of the

National Food Processors Association commenting, ‘‘nothing short of alarming to know that at the

earliest stages of development of crops for PMPs, the most basic preventative measures were not

faithfully observed. This apparent violation of rules. . .very nearly placed the integrity of the food supply

in jeopardy.’’ [18].

As a result of these focusing events, especially the Prodigene fiasco, a certain degree of uncertainty

over the shape of the federal regulatory system was experienced,4 with a concomitant drop in permit

4 The state of Texas, home to Prodigene (College Station, TX) filed Texas House Bill 3387 ‘‘Prohibiting Genetically

Engineered Crops for Drugs, Industrial Chemicals, and other Non-Food Materials’’ on March 14, 2003 [30], 6 days after

USDA-APHIS Federal Register Notice concerning PMPs. This bill, which as of April 10, 2003, was left pending in the House

Agriculture and Livestock committee, would prohibit not only the growing of drugs, industrial chemicals, and other nonfood

materials in crops or livestock normally used as food or animal feed, but would also have banned the production, transport, or

release of these goods in the state of Texas (Texas HR Bill 3387).

P.A. Stewart, A.J. Knight / Technological Forecasting & Social Change 72 (2005) 521–534 529

activity (see Fig. 1) and experimentation with PMPs (see Fig. 2). To address the decreasing trust in the

regulatory structure, OSTP published ‘‘Proposed Federal Actions To Update Field Test Requirements for

Biotechnology Derived Plants and To Establish Early Food Safety Assessments for New Proteins

Produced by Such Plants’’ in August 2002. Specifically, the notice was published to provide guidance to

USDA, EPA, and FDA to update field-testing requirements for food and feed crop plants and establish

early food safety assessments for new plant proteins, most specifically PMPs and PMIPs, in line with the

1986 Coordinated Framework.

According to the document, three principles are relied upon in updating the Coordinated Framework.

First, the level of field test confinement should be consistent with the level of environmental, human, and

animal health risk associated with the introduced proteins and trait(s). Second, if a trait or protein

presents an unacceptable or undetermined risk, field test confinement requirements would be rigorous to

restrict outcrossing or commingling of seed. Further, the occurrence of these genes or gene products

from these field tests would be prohibited in commercial seed, commodities, and processed food and

feed. Finally, even if these traits or proteins do not present a health or environmental risk, field test

requirements should still minimize the occurrence of outcrossing and commingling of seed, although

low levels of genes and gene products could be found acceptable based upon meeting applicable

regulatory standards ([14] p. 50579).

In light of concerns raised by increased experimentation with PMPs and plants expressing industrial

compounds and addressed by OSTP in their notice [14], USDA-APHIS changed rules concerning their

field testing of PMPs in March 2003 [19]. The amount of comments in response to this Federal Register

notice reflects the changing salience concerning the field release of GE plants. While the changes to the

APHIS regulations in 1993 garnered 84 comments and the even more wide-ranging changes in 1997

attracted only 50 comments ([13] p. 104–105), the Federal Register notice concerning PMP field-testing

Fig. 2. Industrial use GE Plants and PMPs.

P.A. Stewart, A.J. Knight / Technological Forecasting & Social Change 72 (2005) 521–534530

requirements attracted at least 847 comments (of which 77 were late), many of them from concerned

citizens. A high percentage of comments were sent by individuals not commonly associated with the

agricultural biotechnology debate, when compared with comments to the previous two Federal Register

notices.

While critiques were raised in many comments by those who appeared to have ties with the organic

movement or with environmental groups such as Greenpeace, as evidenced by the large number of

comments received via email, concerns were raised by other politically powerful groups. GMA and

affiliated groups expressed concern over uncontained field releases of PMPs and PMIPs, especially in

food and feed plants, which account for 75% of all field releases under APHIS notification and permit

regulations. Interestingly enough, while support for a total ban on PMPs was expressed by a small

number of individuals, concern by consumer groups and traditional biotechnology opponents was

tempered, likely mitigated by the potential for medical benefits from this new technology.

While the resulting regulations are expected to be modified further over the coming years, they

currently incorporate significant changes in how PMPs and PMIPs are regulated [20]. Specifically, for all

plants genetically engineered to produce pharmaceutical and/or industrial compounds and field-tested

under permit, APHIS established seven conditions that can be grouped into three categories. The first

considers field test siting, the second considers the dedication of equipment and facilities to their

production, and the third considers procedural matters.

Field test siting regulations proposed by APHIS provide two conditions to be met, with special

consideration for pharmaceutical corn. First, the perimeter fallow zone will be increased from 25 to 50 ft

to prevent inadvertent commingling with plants to be used for food or feed. Second, production of food

and feed plants at the field test site and perimeter fallow zone will be restricted for the following season

to prevent inadvertent harvesting. Furthermore, specific permit conditions for pharmaceutical corn have

been instituted, likely due to corn being the organism of choice, accounting for three quarters of PMP

field releases [1]. The large percentage of experiments with corn derives from a variety of reasons,

including farmer experience and expertise with raising it, the ideal storage nature of its seeds, the large

amount of scientific knowledge concerning its genetics, and the ease in which its genetics are transferred

[1]. The first permit condition requires no corn grown within 1 mile of the test site during any field tests

involving open pollinated corn—an eightfold increase from standards for foundation seed. When pollen

flow is controlled by bagging, the spatial buffer is reduced to 1/2 mile, and a temporal buffer is

established with pharmaceutical corn not to be planted less than 28 days before or 28 days after corn

grown in the zone from the 1/2- to 1-mile boundary. With the establishment of these buffers, whether

they are 1/2 or 1 mile out, border rows will not be allowed to reduce the isolation distance.

A second theme concerns the dedication of farm equipment and facilities to the production of such

crops. First, APHIS requires planters and harvesters to be dedicated to the test site for the duration of

the tests, and although tractors and tillage attachments do not have to be dedicated, they have to be

cleaned in accordance with APHIS protocols. The equipment and regulated articles must be stored in

dedicated facilities for the field tests duration. The final three requirements from the proposed rules

concern procedural aspects of dealing with field tests of PMPs and plants producing industrial

compounds. First, APHIS requires the submission of cleaning procedures to minimize risk of seed

movement. Second, procedures for seed cleaning and drying are required to be submitted and approved

to confine plant material and minimize risk of seed loss or spillage. Finally, permittees will be required

to implement an APHIS-approved training program to successfully comply with the stated permit

conditions [19].

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A key factor in any regulatory arrangement is the ability to ensure that those regulated are complying

with the requirements set forth. As a result of the potentially contentious nature of PMPs and PMIPs,

APHIS plans to increase the number of field site inspections ‘‘to correspond with critical times relevant

to the confinement measures.’’ ([19] p. 11338) Therefore, in addition to maintaining records of activities

related to meeting permitting conditions and increasing the likelihood of auditing them to verify that

required permit conditions were met, APHIS might inspect permitted field tests up to five times during

the growing season—once at preplanting to evaluate the site location, once at the planting stage to verify

site coordinates and adequate cleaning of planting equipment, at midseason to verify reproduction

isolation protocols and distances, at harvest to verify cleaning of equipment and their appropriate

storage, and again at postharvest to verify cleanup of the field site. In addition, two postharvest

inspections may occur to verify that the regulated articles do not persist in the environment. Finally,

APHIS may inspect more frequently if deemed necessary. ([19] p. 11338–11339).

Possibly due to the number of responses received as a result of the Federal Register request for

comments concerning APHIS changing their PMP field release regulations and/or the vehemence of

concern voiced by those participating in the process, the potential for both PMPs and PMIPs entering

into the food supply were cited as points of concern. As a result, and using the PMP regulatory changes

as a starting point, APHIS took immediate action to remove the notification track option, requiring

complete permit track review in their recent (August 6, 2003) interim rule and request for comments. As

stated in the Federal Register notice, ‘‘. . .we believe it is prudent and necessary to remove the

notification option for all industrials pending the completion of our ongoing review of part 340.’’

([21] p. 46435).

The rationale given in the interim rule and request for comments was that while 14 field releases (nine

notifications, five permits) have been carried out to date, the type of genetic engineering being carried

out was to enhance such nutritional components as oil content. However, recent genetic modifications

have been for ‘‘nonfood traits with which APHIS has little regulatory experience or scientific

familiarity.’’ ([21] p. 46434) As such, the definition of PMIPs has three criteria: (1) the plants produce

compounds new to the plant; (2) this compound has not normally been used in food or feed; and (3) the

compound is being expressed for nonfood/feed purposes ([20] p. 46435).

An administrative reorganization of how USDA-APHIS regulates biotechnology recently created the

Biotechnology Regulatory Services (BRS). This reorganization can be seen as another move to address

concerns raised by PMPs and PMIPs specifically and GE organisms generally. According to USDA-

APHIS, ‘‘Given the growing scope and complexity of biotechnology, now more than ever, APHIS

recognizes the need for more safeguards and greater transparency of the regulatory process to ensure that

all those involved in the field testing of GE crops understand and adhere to the regulations set forth by

BRS.’’ Changes instituted by BRS include new training for APHIS inspectors in auditing and

inspections of field trials, the use of new technologies such as global positioning systems, and analysis

of historical trends to inform monitoring and inspection.

According to APHIS, there are six overarching goals that the changes will serve with nine key

components being (1) enhanced and increased inspections in which risk-based criteria, along with other

factors, will be used to assess field test sites, with higher-risk sites being inspected at least once a year

and other sites being randomly selected for yearly inspections; (2) auditing and verification of records of

businesses and organizations to verify accuracy and implementation; (3) remedial measures to protect

‘‘agriculture, the food supply, and the environment in the event of compliance infraction’’ with the

establishment of a ‘‘first-responder’’ group to deal with serious infractions; (4) standardized infraction

P.A. Stewart, A.J. Knight / Technological Forecasting & Social Change 72 (2005) 521–534532

resolution in which criteria will be established to determine the extent of an infraction and the response,

whether this be further investigation, the issuance of a guidance letter, the issuance of a written warning,

or referral to APHIS’ Investigative and Enforcement Services (IES) unit for further action; (5)

documentation, in which a database will be set up to track field test inspections and resulting compliance

infractions; transparency to keep stakeholders and the public informed on the regulatory decision-

making process; (6) continuous process improvements, where as the science of biotechnology advances,

regulations and permit conditions to allow safe field testing will also do so; (7) an emergency response

protocol, being developed with input from EPA and FDA, in which a quick response plan will be put in

place ‘‘to counteract potential impacts on agriculture, the food supply, and the environment’’; (8) training

for field test inspectors in their dealings with PMP and PMIP field test sites, as well as the latest in

auditing; and (9) certification concerning compliance with the highest level of auditing standards [22].

Although the reorganization can be seen as streamlining and focusing enforcement efforts, the

potential for unduly high levels of workload stresses placed on this 26-member unit can be foreseen.

First, BRS draws on APHIS inspectors to inspect field tests; however, more than 2600 of these

agriculture quarantine inspectors have been transferred to the Department of Homeland Security (DHS)

[20]. The current agreement between USDA-APHIS and DHS allows for continued access by APHIS

and BRS, although it can be expected that problems might occur as a result of split responsibilities and

duties.

3. Conclusions

The awareness of the potential for agricultural biotechnology to transform the landscape of American

farming through the development of economically important new products, including PMPs and PMIPs,

has long been recognized. Just less than 10 years ago, this journal devoted a special issue to

‘‘Biotechnology and the Future of Agriculture and Natural Resources’’ [23]. Then, uncertainty over

the future of agricultural biotechnology was based upon the lack of financial support for research and

development as well as vague and unfocused regulations [24]. These same concerns exist now in spite of

better characterized biotechnology-based science and technology and a better understanding of economic

and ecological risks and benefits.

The concerns over the new agricultural biotechnology are often termed as one in which the issue is

less about the science of GE crops and more about the social issues in which this technology is nested.

This ‘‘surrogate for safety’’ is a reflection on the idea that ‘‘in many areas of life there is less and less

control. For some segments food offers some control.’’ [25]. The threat of drugs and medicines, as well

as a variety of industrial compounds, entering the food supply through normal production channels can

be seen as particularly dreaded by the American public, which, while largely unaware of the extent of

genetically modified products in their food supply, have been attenuated to threats to their security since

9-11. In spite of the lack of evidence of human disability through consumption of GE foods, concern has

increasingly been raised in the European Union, which is establishing labeling standards, and Africa,

where GE corn destined for famine relief was turned down due to health and ecological concerns.

While the history of field release of genetically modified plants had been one of technical domination

by insiders, with regulatory change largely ignored by the general public, recent events involving threats

to monarch butterflies by Bt corn, potentially allergenic Starlink Bt corn meant solely for animal feed

entering the U.S. food supply, and PMPs produced by Prodigene nearly entering the American food

P.A. Stewart, A.J. Knight / Technological Forecasting & Social Change 72 (2005) 521–534 533

system have alerted the American public to potential threats, rupturing the previously insular policy

subsystem. While these events provide evidence that the regulatory system is being successfully

implemented, their occurrence has drawn attention to gaps in the Coordinated Framework.

At least two recent events have the potential to further expand the scope of concern and thus conflict.

A report by the Center for Science in the Public Interest (CSPI) called into question the enforcement of

guidelines set by EPA requiring growers using Bt corn to set aside land as refuge for pest management

purposes [26]. Here, corporations have been called upon to regulate farmers directly due to the use of

preexisting pesticide regulations under the Coordinated Framework—a task for which they are not well

suited [27]. And most recently, on November 12, 2003, a coalition of environmental groups and

consumer advocates sued USDA in federal court to stop the field testing of PMPs due to lack of risk

assessment concerning other crops, wildlife, and humans [28].

In light of these concerns and reflected in the rapidly changing field release regulations of PMPs and

PMIPs put forward for comment in the Federal Register in March and August of 2003, there is a high

likelihood that the Coordinated Framework for the Regulation of Biotechnology will continue to change.

Whether this change will occur in the form of marginal alterations in the regulatory approach by EPA,

FDA, and USDA, especially in the case of the latter with the newly constituted APHIS-BRS, while

retaining the Coordinated Framework, or a major change in the regulations through the creation of a new

agency or approach, remains to be seen. As more becomes known about this still young technology and

its potential for health, ecotoxicological and ecological effects, as well as the complex and nonlinear

environment it operates in, the more likely negative side effects will be discovered and dealt with.

Already, both USDA-APHIS and EPA are strengthening their ties with each other with monthly

coordinated phone calls and are enhancing transparency and ties with stakeholders through public

workshops and meetings. Additionally, greater attention is being given to different means of approaching

ecological control of these products, in light of a newly released National Academy of Sciences report on

the biological confinement of GE organisms [29].

Regardless, new agricultural–environmental biotechnologies stand on a precipice of change. Over the

next 15 years, they may continue to change how food, drugs, and industrial products are produced, or

they may be yet another failed technology along the lines of nuclear power with its plants withdrawn

from farmers’ fields, depending on how issues dealing with public trust in regulations are addressed. In

either case, it is social support for the technology and trust in regulatory institutions that matter most.

Acknowledgements

This report was funded by the Arkansas Biosciences Institute, Arkansas State University.

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