|How to Approach the Regulatory Conundrum?
By Gregory A. Jaffe, Director, Biotechnology Project
presented at the National Agricultural Biotechnology Council's Foods for Health conference May 19, 2002.
Today, farmers and the environment benefit from the first generation of agricultural
biotechnology crops. The biotechnology industry and academics trumpet the next generation of
genetically engineered ("GE") crops, such as more nutritious foods and plants used to produce
pharmaceuticals, antibodies and industrial enzymes. If those crops are commercialized, is the current
regulatory structure in the United States up to the task of ensuring that those products are safe for
humans and the environment? This paper analyzes the ability of the regulatory system to adequately
regulate the next generation of agricultural biotechnology products. It concludes that without additional
legal authority and stronger oversight, the US regulatory system cannot ensure that only agricultural
biotechnology products that are safe for humans and the environment are commercialized.
I. What the Future Holds?
Virtually every week there is media coverage about new applications for agricultural
biotechnology. Some applications add new genes to crops to make food more nutritious. For
example, in the past year, the press has reported on the following potential products:
- Scientists have inserted two genes from a daffodil and one from a bacterium into rice plants
to create golden rice. That rice produces beta-carotene, which the human body turns into
- At University of California at Davis, scientists have modified rice plants to carry a human
gene for a milk enzyme called lactoferrin. Rice containing that human breast milk protein
may be helpful in fighting infections.
- In Australia, one of the four primary protein genes present in cows has been inserted into
calves to enable production of high protein milk. Those cows may produce more nutritious
- Researchers are trying to increase the anti-oxidant properties of tomatoes by engineering
them with more lycopene and increased levels of lutein (known to help fight eye disease).
Research is also being conducted so that agricultural crops can be employed as factories to
produce biological molecules in a cost-efficient and renewable manner. For example:
- Prodigene has engineered corn plants to produce avidin and trypsin. Avidin, which is
usually found in egg whites, is used in medical and biochemical diagnostics. Trypsin is an
industrial enzyme used to produce drugs.
- Epicyte is currently engineering plants to produce antibodies, such as a topically applied
antibody that prevents the transmission of herpes simplex virus.
- Hiridin, an anticoagulant, has been produced in transgenic canola and is available
commercially in Canada. That human protein is used to treat blood clots.
- In April, a company announced that it has produced a genetically engineered corn that
contains a protein on the surface of HIV, the virus that causes AIDS. The next step for that
edible vaccine is animal studies to see if ingestion of the corn elicits an immune response.
Other crops, such as bananas and carrots, are also being engineered to produce vaccines.
Those potential products and many others provide some hope that the next generation of
products may benefit consumers, both in developed and developing countries. If those products are
commercialized, fruits, vegetables, and grains will become vehicles that provide consumers with more
nutritious and healthful foods and biological factories that produce useful medical and industrial
II. Is the Regulatory Structure Up to the Task of Regulating New Uses of Agricultural
Currently, agricultural biotechnology is regulated to protect human health and the environment.
Is the current federal regulatory system up to the task of thoroughly assessing the safety to humans and
the environment of the next generation of GE crops? A review of the regulatory system's treatment of
the first generation of biotech crops identifies both weaknesses and gaps in the current system and
problems that will arise when regulating future crops. New statutory authority and stronger oversight is
needed to ensure that only commercial products that are safe for humans and the environment are
III. Ensuring that GE crops are Safe to Eat
Consumers want assurance that the foods they eat are safe to consume. Thus, the Food and
Drug Administration ("FDA") should ensure the safety of biotech foods before they are marketed to
them. FDA's current regulatory system, however, does not adequately ensure that only safe GE crops
A. Current Regulation of Biotech Foods
Currently, FDA does not formally approve any GE crops as safe to eat. FDA has the authority
to approve new food additives, but says that the GE crops developed so far do not fall within that
authority. Instead, FDA has determined that GE crops are similar to conventionally bred crops and
should typically fall into the category of "generally recognized as safe" ("GRAS") foods. FDA's policy
does allow a GE crop to be treated as a food additive requiring mandatory approval if that crop raises
a food-safety concern. However, to date, FDA has not determined that any GE crop should be
considered a food additive and it is unclear if any future crop will fall into that category. Both FDA and
the biotechnology industry will strongly resist putting biotech foods through the food additive process,
since that process is perceived as time-consuming and burdensome.
To oversee any potential food-safety concerns that might exist for a GE crop, FDA adopted a
voluntary consultation process to review safety data provided by companies to ensure compliance with
existing laws. In that process, the biotechnology company provides summary information about the
food-safety of its product to FDA and FDA provides informal advice about the adequacy of the tests
conducted by the company. In conducting its scientific safety assessment, the company provides
information to show that its biotech variety is "substantially equivalent" or as safe as its conventionally
bred counterpart. To date, almost all commercialized GE crops have proceeded through the voluntary
consultation process before marketing.
B. Problems with FDA Current Biotechnology Policy
There are numerous problems with FDA's current policy for GE crops. First, the consultation
process is voluntary. There is no legal obligation that requires that companies provide a safety
assessment to FDA and no consequences to a company if they do not voluntarily consult. Second, the
consultation process is developer-driven instead of FDA-driven. The biotechnology company decides
what safety tests to conduct and what data to submit to FDA because the company's obligation is to
satisfy itself that the product is safe rather than prove safety to FDA. The voluntary process provides
FDA with limited ability to require specific tests or mandate specific data. Third, FDA's food-safety
analysis is not comprehensive. FDA guidance states that the consultation process is "not a
comprehensive scientific review of the data generated by the developer." Fourth, and most importantly,
FDA does not determine if the product is safe. The voluntary consultation process culminates with
FDA stating that it has "no further questions . . . at this time" regarding the food instead of a statement
that the product is safe to eat.
Although no human health problems with GE crops have been detected, the voluntary
consultation process is not the most effective way to protect human health and engender public
confidence. As the next generation of GE crops are marketed in the coming years, the scientific safety
issues raised by those more complex GE crops (such as nutritionally enhanced crops or plants
engineered with new metabolic pathways) cannot be adequately assessed with this industry-driven
C. FDA's Recently Proposed Mandatory Notification Rule
In January 2001, FDA proposed regulations that would mandate notification before a GE food
is marketed. Although that proposal improves upon the current process by mandating agency review
and increasing transparency, it does not change the agency's scientific review nor will it result in an
official safety determination. Under the mandatory notification, FDA still does not respond with an
affirmation that the food is safe to eat. Also, if a developer markets a biotech food without notifying
FDA, FDA still must prove the food is adulterated before it can be removed from commerce.
D. How Will the Current System Treat the Second Generation of Biotech
As products such as golden rice or high lycopene tomatoes make their way to the marketplace,
will FDA's current regulatory policy treat them any differently than the first generation of herbicide-resistant and pesticide-producing crops? The answer is no. It is unlikely that FDA will treat the second
generation of GE food crops as products that contain food additives since the gene products in high
lycopene tomatoes or rice engineered to contain a human breast milk protein are substances normally
found in the human diet. Thus, the only food-safety assessment those products will receive is the less-than-comprehensive voluntary consultation process. Those products would have to abide by the
mandatory notification process, but only if FDA finalizes that proposed rule. FDA has stated that it will
not make a decision on its proposed rule before sometime in fiscal year 2003 and no one knows what
form the final rule will take if promulgated.
E. A Proposal for a Mandatory Approval Process
FDA should establish a new mandatory approval process, unrelated to the current food
additive process, for GE crops. FDA should promulgate regulations that establish testing and data
requirements based on advice from a National Academy of Sciences panel of scientists charged with
determining what scientific information is needed to assess the food-safety concerns of such crops. The
approval process should have time limits so that each submitted application receives a determination
from FDA in a reasonable period of time. In addition, the mandatory approval process should ban any
biotech food with a new allergen as well as prohibit approvals for crops intended for animal feed but
not human consumption. If new legislation is needed so that FDA can implement an approval process,
Congress should pass such legislation.
A mandatory pre-market approval process at FDA for biotech foods would have numerous
advantages over the current system. First, an approval by FDA would provide an independent check
on industry's safety determination. FDA would share responsibility for the safety determination and
would help prevent food-safety mistakes. Second, it eliminates the gap in the U.S. regulatory system
which allows some biotech foods, but not others, from being marketed without pre-approval. Currently
transgenic animals require pre-market approval by FDA and pesticidal plants require pre-market
approval by the Environmental Protection Agency, yet non-pesticidal transgenic plants only need go
through FDA's voluntary consultation process. Third, an approval process would not be more
burdensome to applicants than the current voluntary process. The industry states that it already
conducts all reasonable and necessary tests to ensure safe products, so there is little likelihood that
FDA would require significant new testing. Fourth, a mandatory approval process would conform the
US regulatory system to similar systems in Canada and Europe, which affirmatively approve biotech
foods before marketing. Finally, a food-safety determination by FDA would go a long way to
improving consumer confidence and public perception of the safety and acceptability of biotech foods.
Consumers are much more comfortable with FDA determining a food is safe to eat that relying on
Monsanto or Dupont's own safety determination.
In conclusion, the benefits of a properly constructed mandatory approval process at FDA are
tremendous and the burdens to industry need not be much greater than the current voluntary
consultation process. It is unclear why industry is against a process which would provide an
independent verification of their product's safety and sway skeptical consumers. Therefore, producers
of new GE crops should embrace sensible legislation to require a mandatory approval of GE crops,
such as Senator Durbin's Genetically Engineered Foods Act.
IV. Environmental Issues Surrounding GE Crops
The second major regulatory issue for new GE crops is ensuring that those crops do not cause
environmental problems. For the federal regulatory system to adequately carry out that function, the
- Ensure that all biotech products get a thorough environmental assessment by a
competent government agency before release into the environment; and
- Ensure that if products are approved with conditions to manage possible environmental
risks, those conditions are adhered to (through compliance assurance and enforcement
Unfortunately, the current federal regulatory system for GE crops at the U.S. Department of Agriculture
("USDA") falls short on both accounts.(2)
A. The Current Regulatory System at USDA
Under the authority of the Plant Pest Act, USDA has established a regulatory system for
genetically engineered plants that could become plant pests. Crops subject to those regulations include
(1) any crop that is a listed plant pest, and (2) any crop that has introduced DNA from a listed plant
pest or an organism whose plant pest status is undetermined. For example, the regulations capture any
genetically engineered crop that uses agrobactium DNA as part of its genetic construct to insert a new
gene into a plant. The regulations do not include crops engineered using a gene gun, unless the inserted
DNA comes from a listed plant pest or an organism whose plant pest status is undetermined.
Any plant covered by USDA's regulation must submit to one of three oversight processes
before release into the environment. The first of those processes is a notification, in which the applicant
provides USDA with details about its proposed release and USDA has thirty days to respond to the
notification. USDA has established criteria to determine which products are eligible for the notification
process and guidelines that must be met to minimize environmental effects from the release. Notification
is currently used to regulate virtually all of the field tests for GE crops under USDA's jurisdiction and
even for some crops that are grown commercially.
The second process is permitting, which requires a more detailed application and a longer
review time at USDA before the release is authorized. Genetically engineered plants that must be
permitted (instead of a notification) include crops producing pharmaceuticals and those that could affect
non-target organisms. Permitting is not used as commonly as the notification process, although
hundreds of permits have been issued since USDA began regulating GE crops.
The third process at USDA is a petition for non-regulated status. A petition is a request that
USDA determine that there is no plant pest risk associated with the crop and that the crop no longer
needs to be regulated. A petition for non-regulated status has been the primary pathway to
commercialize GE crops. Before a petition is granted, USDA conducts an environmental assessment of
the crop and seeks public input through a formal public comment period.
B. Inadequacies with USDA's Current System
There are numerous inadequacies with USDA's current regulation of GE crops. First, the
regulatory system only captures GE crops that could become plant pests, leaving a gap in USDA's
authority so that some GE crops, such as those made with a gene gun and corn DNA, do not require
even a notification before release into the environment.
Second, for GE crops covered by USDA's regulations, those regulations do not require that a
thorough environmental assessment occur prior to the plant's release into the environment. Crops
released through either the notification or the permitting process almost never receive an individual
environmental assessment, yet some of those crops might have significant environmental impacts. A
recent National Research Council ("NRC") report determined that "With few exceptions, the
environmental risks that might accompany future novel plants cannot be predicted. Therefore, they
should be evaluated on a case-by-case basis." Yet, the notification and permitting process does not
evaluate environmental risks on a case-by-case basis since no environmental assessment is conducted
for most individual applications processed using those procedures.
Third, for those crops that do receive a thorough environmental assessment from USDA
(consisting primarily of crops that seek nonregulated status), those environmental assessments are
inadequate. According to the NRC report: "Currently, APHIS environmental assessments focus on the
simplest ecological scale.... APHIS should includeany impact on regional farming practice or systems in
its deregulation assessments." Thus, USDA's environmental assessments do not address all relevant
Fourth, it is unclear whether USDA has the legal authority to adequately address environmental
issues that arise in an environmental assessment. USDA has regulatory authority to address plant pest
risks but does not have authority to prevent a crop's release if it may cause ecological harms unrelated
Fifth, most large-scale releases occur after the GE crop has obtained nonregulated status.
Although the petition process for nonregulated status is transparent, open for public comment, and
involves an environmental assessment, the process results in a crop that is no longer regulated by
USDA. That prevents USDA from requiring post-release monitoring for environmental effects and
from addressing environmental issues that might occur. Therefore, for the vast majority of crops,
USDA has extremely limited ability to address environmental issues that might arise after
Finally, the process at USDA involves no food-safety analysis of the crop before it is released
into the environment. For open-pollinating crops such as corn, a release could result in the gene
product entering the food chain. USDA's process makes no assessment whether that gene product will
be harmful to humans if it does enter the food supply.
C. Preventing Contamination of Other Crops and the Food Supply from
Experimental GE Crops and/or GE Crops Producing Non-food Products.
When USDA regulates a GE plant under either the notification or the permitting process, one of
USDA's goals is "to minimize persistence in the environment and inadvertant mixing with ... products
which are used for food or feed." This is accomplished, in part, by using containment and/or
segregation procedures. Those procedures may limit contamination but do not eliminate it, since
eliminating all contamination is impossible.
The ability of the regulatory system to adequately contain GE plants producing products that
might harm the environment or humans is extremely important, whether it is a corn plant producing a
pharmaceutical or a sunflower plant producing an industrial chemical. USDA and FDA have stated
they are working on a guidance that will address contamination issues surrounding pharmaceutical
plants but that guidance currently is not publicly available. Yet, numerous field trials and commercial
planting of pharmaceutical crops have occurred without uniform standards to minimize contamination.
Consumers will lose confidence in agricultural biotechnology and the safety of the food supply if they
find out that some food they are eating contains a pharmaceutical or industrial chemical that has not
been found safe to ingest. Thus, strong regulatory structures that minimize contamination are important.
1. Containment Procedures
The first way to minimize the effects of GE crops on non-GE crops and the food supply is
through containment procedures. Those procedures attempt to limit gene flow of the introduced gene.
Containment procedures include reproductive isolation measures, such as distance restrictions for
planting GE crops from non-GE crops, guard rows between GE and non-GE crops, the use of male
sterile lines that don't shed pollen, harvesting prior to flowering, netting or bagging of pollen prior to
flowering, and the staggering of flowering times for adjacent crops.
For example, USDA recently sent a letter to companies planning on planting pharmaceutical
corn crops in 2002 that set forth distance restrictions that ranged from 1/4 mile to 5 miles (the latter
being the distance from seed corn) and planting times for the GE corn that were either 14 or 21 days
before or after adjacent non-GE corn crops. The letter, however, contained no scientific justification
for the distances or planting times chosen nor set forth how effective those restrictions would be in
reducing or eliminating contamination of non-GE crops. It is unclear whether those distances and
planting times will reduce the chances of gene flow by 50%, 90%, or 99%. Thus, although
reproductive isolation is necessary and needs to be established, there should be a public explanation
why certain procedures are required and what is the expected benefit of those procedures.
The second type of containment procedures that minimize persistence of the GE crop in the
environment are post-harvest restrictions. Post-harvest restrictions include limiting the use of land for a
period of time following the planting, monitoring the land and neighboring fields for volunteer plants of
the GE crop, and destroying the crop after harvest using specific procedures. Those post-harvest
restrictions are important to prevent GE crops from persisting in the environment after the field trial or
commercial planting. It is unclear, however, how effective those activities are in preventing gene
In addition to containment procedures, segregation is usually employed to ensure that
experimental GE-crops and GE-crops producing non-food products do not mix withe crops (both GE
and conventional) that are grown for food purposes. Segregation has generally involved dedicated
machinery and vehicles to harvest, store and transport certain GE-crops.
Is segregation effective in preventing contamination? When farmers planted the GE corn called
StarLink that had been only approved for feed uses, Aventis (the developer of StarLink) agreed that
the crop would be segregated from corn used for human consumption. StarLink corn, however, did
end up in the food supply, either because no segregation system was actually put in place or because
the system that was put in place was ineffective. Many experts now question whether any segregation
system can effectively separate out one type of corn from another. Thus, it is an open question how
effective segregation can be at eliminating contamination of the food supply. If properly set up,
segregation can minimize contamination, but may never be able to completely eliminate it.
When a GE crop has been approved to be released into the environment, frequently the
approval sets forth conditions to minimize or eliminate environmental and/or food-safety risks. It is
imperative that developers and growers comply with those conditions and it is USDA's job to make
sure those conditions are being adhered to. Is USDA doing a good job enforcing its conditional
approvals? The answer is no.
USDA has conducted some inspection of field trials and commercial releases that have permits
or submitted notifications, although the level of effort is small compared to the universe of GE crops.
To date, there have been over 9,000 permitted releases or notifications for GE crops, yet only a very
small fraction of those releases have been inspected by USDA. The inspections USDA has conducted
have resulted in approximately 60 enforcement actions, primarily letters explaining improper conduct
and requesting that restrictions be adhered to.
When USDA does inspect a permitted release, however, it is unclear whether those inspections
are as comprehensive as needed to safeguard the environment. In particular, USDA does not check to
see if the containment or segregation procedures are working. For example, inspectors do not check
neighboring fields to see if pollen has drifted and caused gene flow to non-GE crops. Also, they do not
test grains on the farm or neighboring farms to ensure that the crop has been properly segregated.
Thus, USDA should not just inspect to see if the conditions imposed on a GE-crop have been met, but
whether those conditions result in the containment and segregation expected from the proper
implementation of those conditions.
E. Conclusions About USDA's Regulation of GE Crops
USDA's regulations do not adequately protect the environment and humans from current GE
crops and will not adequately protect the environment and humans from the next generation of crops,
such as those producing pharmaceutical plants. In particular, the USDA regulatory system has the
- It does not capture all GE crops;
- It does not result in a thorough environmental assessment for all GE crops;
- It does not have a mechanism for the monitoring of environmental problems that might arise
after a crop has obtained nonregulated status, nor a means of enforcement if a problem
- It does not conduct inspections to identify whether containment procedures to minimize
gene flow from GE crops and segregation requirements to minimize food contamination
from certain GE crops are effective.
Until those deficiencies are eliminated, the federal government will not be adequately ensuring that the
only GE crops released into the environment are safe to humans and the environment.
V. What to Do About GE Crops that are not Intended to be Food but Might End Up in the
As discussed earlier, the next generation of biotech crops will use food crops to produce non-food products, such as pharmaceutical plants or plants engineered to produce medical diagnostic
proteins. What happens if those crops accidentally end up in the food supply due to gene flow from
pollen, contamination of seed stock, or a breakdown in an identity-preserved segregation system? Will
they be safe to consume? Will they be safe to consume only at certain exposure levels? Is there any
authority for FDA to review and approve those products as safe to eat in case they enter the food
supply? Those are all questions that need to be addressed. Containment and segregation will not be
100% effective, so it is only a matter of time before one or more of the non-food GE crops ends up in
our food supply.
The Federal Food Drug and Cosmetic Act ("FFDCA") regulates anything that is intended to be
used as food or feed. A pharmaceutical corn plant or a corn plant producing avidin, however, is not
intended by the developer to be used as food or feed. Thus, those products are neither food additives,
nor would they be subject to FDA's voluntary notification process (or FDA' s proposed mandatory
notification rule). FDA has limited authority over those products unless they show up in food. At that
stage, FDA could consider foods containing the pharmaceutical drug or industrial chemical adulterated
and remove them from the market. The burden would be on FDA, however, to prove they are
The current system is not the best way to ensure a safe food supply, when contamination by
non-food GE crops is inevitable. A possible solution to this problem would be for the proposed
mandatory FDA approval process to apply to non-food GE crops. Under that approval system, FDA
could set tolerances for non-food GE crops. Then, if that GE crop entered the food supply, eating the
engineered substance would be safe as long as the substance was below the tolerance level. No
consumers would need to fear that they were eating food with unsafe substances in it. In addition, the
rigor of the food-safety assessment conducted by FDA could be proportionate to the physical and
biological confinement of the crop. If the pharmaceutical plant was grown in a cave or a location far
from other corn plants, only a limited food-safety assessment might be required because the likelihood
of contamination would be extremely small. If the pharmaceutical plant was grown in Iowa, however,
then a complete food-safety analysis might be warranted.
Although agricultural biotechnology may allow us to produce more nutritious foods and useful
medical products, the current federal regulatory structure is not up to the task of safeguarding those
products. With new legal authority and better regulations, a strong, but not stifling, system can be
established that independently reviews and approves products that are safe for consumers and the
environment. Such a system is essential if consumers are to have confidence in biotechnology and
accept biotechnology products in the marketplace.
1 Although the next generation of biotechnology crops includes the production of drugs and the delivery
of vaccines, the drugs and vaccines produced will be regulated similarly to conventionally produced drugs
and vaccines. Therefore, this presentation will not include a discussion of those regulatory issues.
2 This presentation will focus on the USDA regulatory process for biotech crops and does not discuss
EPA's regulatory structure for plants engineered to contain a pesticide.