Report to Congressional Requesters

United States General Accounting Office

GAO

May 2002 GENETICALLY

MODIFIED FOODS

Experts View Regimen

of Safety Tests as

Adequate, but FDA's

Evaluation Process

Could Be Enhanced

GAO-02-566
Page i GAO-02-566 Genetically Modified Foods

Letter 1

Results in Brief 2

Background 4

GM Foods Share the Same Types of Health Risks as Conventional

Foods and Are Evaluated by Tests That Appear Adequate 9

FDA Believes That It Obtains Necessary Safety Data for GM Food

Evaluations, but FDA’s Overall Evaluation Process Could Be

Enhanced 18

Future Changes in GM Foods May Alter Their Composition and

Require New Testing Technologies for Assessing Safety 25

Experts Maintain That Long-Term Monitoring of GM Foods Is

Neither Necessary nor Feasible 30

Conclusions 32

Recommendations for Executive Action 32

Agency Comments 33

Appendix I Objectives, Scope, and Methodology 35

Appendix II Potential Use of Metabolic Profiling to Compare a

GM Plant to Its Conventional Counterpart 38

Appendix III Comments from the Department of Health and

Human Services 43

Appendix IV GAO Contacts and Staff Acknowledgments 46

Related GAO Products 47

Tables

Table 1: GM Foods for Human Consumption Evaluated by FDA 6

Contents
Page ii GAO-02-566 Genetically Modified Foods

Figures

Figure 1: Use of Biotechnology to Create a Pest-Resistant Plant 5

Figure 2: Example of the Regimen of Tests Used for Safety

Assessments of GM Foods 13

Figure 3: Metabolic Profiling of Three GM Mustard Plant Varieties

in Comparison with Baseline Data from Their

Conventional Counterparts 39

Abbreviations

APHIS Animal and Plant Health Inspection Service

CFSAN Center for Food Safety and Applied Nutrition

DNA deoxyribonucleic acid

EPA Environmental Protection Agency

FAO Food and Agriculture Organization

FDA Food and Drug Administration

GM genetically modified

PBN Pre-Market Biotechnology Notice

RNA ribonucleic acid

USDA U.S. Department of Agriculture

WHO World Health Organization
Page 1 GAO-02-566 Genetically Modified Foods

May 23, 2002

The Honorable John E. Baldacci

The Honorable John F. Tierney

House of Representatives

Proponents and opponents of modern agricultural biotechnology hold

passionate views about the benefits and risks of using this technology to

produce genetically modified (GM) food.1

 Proponents cite enhanced crop

yields, more environmentally friendly food production, and more

nutritious foods as reasons to move forward. Opponents of biotechnology

argue that not enough is known about the safety of these foods and that

they should be more rigorously controlled.

While confidence in the safety of GM foods is essential to their commercial

success, governments and consumers from different parts of the world

have taken very different positions on their safety and regulation. Some

consumers in Western Europe have shown their opposition to this

technology by destroying GM food crops, and European regulatory entities

have not approved any new GM foods in the past several years. In the

United States, consumers and regulatory agencies, such as the Food and

Drug Administration (FDA), generally support GM foods, with a number of

these foods having been made available for sale in recent years. However,

the debate on the safety of these foods is ongoing and may intensify in the

future as genetic modifications to foods become increasingly complex.

To ensure public confidence in GM foods, the U.S. biotechnology industry

recognized in the early 1990s the need for oversight by FDA, which has

primary responsibility for the safety of most of the nation’s food supply.2

 In

response, FDA published guidelines in 1992 to ensure that companies

developing GM foods worked with the agency in assessing the safety of

these foods. As part of the process, companies test new GM foods to

 1

 Modern agricultural biotechnology is a collection of scientific techniques, such as genetic

engineering, used to modify plants, animals, or microorganisms by introducing desired

traits in them, including characteristics from unrelated species. For example, traits may be

introduced to facilitate pest management and improve yield or nutritional value. In this

report, we will refer to food derived from genetically modified plants as GM foods.

2

 The U.S. Department of Agriculture’s (USDA) Food Safety and Inspection Service is

responsible for ensuring the safety of meat, poultry, and egg products. FDA is responsible

for all other foods, including seafood.

United States General Accounting Office

Washington, DC 20548
Page 2 GAO-02-566 Genetically Modified Foods

assess their safety, including their potential health risks, and submit test

data to FDA for evaluation.3

 As of April 2002, FDA has evaluated 50 GM

foods, many of which have subsequently been placed on the market.

Currently, submission of information to FDA is voluntary, but FDA

published a proposed rule in January 2001 that would make this

submission mandatory.

In light of the continued debate about GM foods, you asked us to (1)

identify the types of potential human health risks associated with GM

foods and experts’ views regarding the adequacy of tests used to evaluate

these risks, (2) describe FDA’s controls for ensuring that companies

submit test data it requests and identify experts’ views of the agency’s

overall evaluations of these foods, (3) describe potential changes in future

GM foods and any associated changes in tests to evaluate them, and (4)

identify experts’ views on the necessity and feasibility of monitoring the

long-term health risks of these foods.

To conduct this work, we reviewed scientific and technical studies and

other literature and spoke with experts in government, academia, private

industry, and consumer groups. We selected these experts in consultation

with officials from the National Academy of Sciences. As agreed with your

offices, we did not assess the potential environmental risks associated

with GM food production. In addition, since there have been no GM

animals evaluated for commercialization, we did not assess their potential

environmental or human health risks. Also, we did not independently

evaluate FDA’s controls for ensuring it receives safety data. Further details

of the scope and methodology of our review are discussed in appendix I.

GM foods pose the same types of inherent risks to human health as

conventional foods: they can contain allergens, toxins, and compounds

known as antinutrients, which inhibit the absorption of nutrients. Before

marketing a GM food, company scientists evaluate these risks—even

though they are not routinely evaluated in conventional foods—to

determine if the foods pose any heightened risks. While some GM foods

have contained allergens, toxins, and antinutrients, the levels have been

comparable to those foods’ conventional counterparts. In evaluating GM

foods, scientists perform a regimen of tests. Biotechnology experts whom

 3

 In general, risk assessment involves several steps, including identifying the hazard (type

of risk) and assessing the level of exposure to the hazard.

Results in Brief
Page 3 GAO-02-566 Genetically Modified Foods

we contacted agree that this regimen of tests is adequate in assessing the

safety of GM foods. While some consumer groups, as well as some

scientists from the European Union, have questioned the ethical or

cultural appropriateness of genetically modifying foods, experts whom we

contacted from these organizations also believe the tests are adequate for

assessing the safety of these foods.

While FDA reports that its evaluation process includes the necessary

controls for ensuring it obtains the safety data needed to evaluate GM

foods, some biotechnology experts state that aspects of its evaluation

process could be enhanced. FDA’s controls include (1) communicating

clearly—through the agency’s 1992 policy statement and subsequent

guidance—what safety data are necessary for its evaluations of GM food

safety; (2) having teams of FDA experts in diverse disciplines evaluate

company submissions for GM foods and request additional safety data, if

necessary; and (3) tailoring the level of evaluation to match the degree of

each submission’s novelty, thereby assuring that staff have time to obtain

necessary safety data. Nonetheless, FDA’s overall evaluation process

could be enhanced, according to some experts, by randomly verifying the

test data that companies provide and by increasing the transparency of the

evaluation process—including communicating more clearly the scientific

rationale for the agency’s final decision on a GM food safety assessment.

In the future, scientists generally expect that genetic modifications will

increasingly change the composition of GM foods to enhance their

nutritional value. For example, one company has modified a type of rice to

contain beta-carotene. In countries where rice is a dietary staple, this rice

may reduce the incidence of blindness caused by vitamin-A deficiency.

Current tests have been adequate for evaluating the few GM foods with

relatively simple compositional changes that FDA has reviewed so far.

New testing technologies are being developed to evaluate the increasingly

complex compositional changes expected. Some scientists view these new

technologies as a potentially useful supplement for existing tests, while

others believe that the technologies will offer a more comprehensive way

of assessing the safety of all changes in GM foods.

Monitoring the long-term health risks of GM foods is generally neither

necessary nor feasible, according to scientists and regulatory officials we

contacted. In their view, such monitoring is unnecessary because there is

no scientific evidence, or even a hypothesis, suggesting that long-term

harm (such as increased cancer rates) results from these foods.

Furthermore, there is consensus among these scientists and regulatory

officials that technical challenges make long-term monitoring infeasible.
Page 4 GAO-02-566 Genetically Modified Foods

Experts cite, for example, the technical inability to track the health effects

of GM foods separately from those of their conventional counterparts. A

recent report by food and health organizations affiliated with the United

Nations also expresses skepticism about the feasibility of identifying longterm health effects from GM foods.

This report contains recommendations to the Deputy Commissioner of

Food and Drugs for enhancing the effectiveness of FDA’s safety

evaluations of GM foods. The recommendations concern the need to

randomly verify test data and increase the transparency of the agency’s

safety evaluations of these foods. In commenting on a draft of this report,

FDA agreed with our recommendations and stated that the

recommendations would increase the transparency of, and public

confidence in, FDA’s evaluations of GM foods. FDA also provided

technical comments which we incorporated as appropriate.

Modern agricultural biotechnology refers to various scientific techniques,

most notably genetic engineering, used to modify plants, animals, or

microorganisms by introducing into their genetic makeup genes for

specific desired traits, including genes from unrelated species. For

centuries people have crossbred related plants or animal species to

develop useful new varieties or hybrids with desirable traits, such as better

taste or increased productivity. Traditional crossbreeding, however, can

be very time-consuming because it may require breeding several

generations to obtain a desired trait and breed out numerous unwanted

characteristics. Genetic engineering techniques allow for faster

development of new crop or livestock varieties, since the genes for a given

trait can be readily introduced into a plant or animal species to produce a

new variety incorporating that specific trait. Additionally, genetic

engineering increases the range of traits available for developing new

varieties by allowing genes from totally unrelated species to be

incorporated into a particular plant or animal variety.

In the 1970s, scientists learned how to extract a specific gene from a DNA

strand and insert this gene into a different organism where it would

continue to make the same protein that it did in its original organism.

Scientists have applied this technology to bacteria, plants, and animals.

For example, as shown in figure 1, scientists produced pest-resistant

plants by identifying a gene responsible for pest resistance in an organism,

isolating and copying the gene, and then inserting it into the target plant’s

DNA. The plant was then tested to determine that the transferred trait

Background
Page 5 GAO-02-566 Genetically Modified Foods

(transgene) was inherited in subsequent generations and that the

“transgenic” plant grew and functioned as well as the conventional variety.

Figure 1: Use of Biotechnology to Create a Pest-Resistant Plant

Biotechnology offers a variety of potential benefits and risks. It has

enhanced food production by making plants less vulnerable to drought,

frost, insects, and viruses and by enabling plants to compete more

effectively against weeds for soil nutrients. In a few cases, it has also

improved the quality and nutrition of foods by altering their composition.

Table 1 summarizes the GM foods evaluated by FDA.
Page 6 GAO-02-566 Genetically Modified Foods

Table 1: GM Foods for Human Consumption Evaluated by FDA

Modified Attribute

Insect

Resistance

Viral

Resistance

Herbicide

Tolerance

Modified

Oil

Plant

Reproductive

Sterility

Delayed

Ripening/

Softening

GM Plant Product—# of Plant

Varieties

Corn—8

Tomato—1

Potato—4

Cotton—2

Squash—2

Papaya—1

Potato—2

Corn—9

Rice—1

Canola—8

Sugar Beet—2

Flax—1

Cottona

—4

Radish—1

Soybean—2

Soybean—1

Canola—1

Corn—3

Canola—3

Radish—1

Cantaloupe—1

Tomato—4

Totalb15 5 28 2 7 5

a

Cotton seed has been used as a protein source in candy.

b

Fifty products have been evaluated, as of April 2002. The total number of modified attributes is 62

because several products were modified with multiple attributes.

Source: GAO analysis of FDA data.

Table 1 shows that the majority of modifications have been aimed at

increasing crop yields for farmers by engineering a food plant to tolerate

herbicides or attacks from pests such as insects and viruses (48 out of 62

modifications). Further, only two food plants have been altered to produce

modified oil: the soybean and canola plants. According to industry

officials, the modified soybean produces healthier oil. They also stated

that the canola plant was modified to have a domestic source for laurate

cooking oil.4

 Because soybean oil is the most commonly consumed plant

oil worldwide, scientists say that the new oil could significantly improve

the health of millions of people.

For three key crops grown in the United States—corn, soybeans, and

cotton—a large number of farmers have chosen to plant GM varieties. In

2001, GM varieties accounted for about 26 percent of the corn, 68 percent

of the soybeans, and 69 percent of the cotton planted in the United States.

These crops are the source of various ingredients used extensively in

many processed foods, such as corn syrup, soybean oil, and cottonseed

oil, and they are also major U.S. commodity exports. The United States

accounts for about three-quarters of GM food crops planted globally.

 4

 Laurate canola oil is a form of canola oil that contains lauric acid, a fatty acid found in

tropical oils. As a result, laurate canola oil can substitute for palm kernel oil which is an

imported tropical oil.
Page 7 GAO-02-566 Genetically Modified Foods

However, the use of biotechnology has also raised concerns about its

potential risks to the environment and people. For example, some people

fear that common plant pests could develop resistance to the introduced

pesticides in GM crops that were supposed to combat them. Further, some

fear that crops modified to be tolerant to herbicides could foster the

evolution of “super weeds.” Finally, some fear that scientists might

unknowingly create or enhance a food allergen or toxin. Therefore, as

biotechnology was being developed, U.S. scientists, regulators, and

policymakers generally agreed that GM plants should be evaluated

carefully before being put into widespread use. As a result, the United

States published a Coordinated Framework for Regulation of

Biotechnology in 1986. This framework outlined the regulatory approach

for reviewing GM plants, including relevant laws, regulations, and

definitions of GM organisms.

Responsibility for implementing the coordinated framework fell primarily

to three agencies: USDA, the Environmental Protection Agency (EPA), and

FDA. Within USDA, the Animal and Plant Health Inspection Service

(APHIS) bears the main responsibility for assessing the environmental

safety of GM crops. The primary focus of APHIS’ review is to determine

whether or not a plant produced through biotechnology has the potential

to harm natural habitats or agriculture. Developers can petition APHIS to

exempt a GM plant from regulation once sufficient and appropriate data

have been collected regarding the potential environmental impact of a GM

plant.

To safeguard the environment and human health, EPA is responsible for

regulating genetic modifications in plants that protect them from insects,

bacteria, and viruses. These protectants are subject to the agency’s

regulations on the sale, distribution, and use of pesticides. EPA must

review and grant a permit for field-testing plants with such protectants on

more than 10 acres of land. Prior to commercialization of a GM plant with

such a protectant, EPA reviews the application for approval of the

protectant, solicits public comments, and may seek the counsel of external

scientific experts.

FDA has primary authority for the safety of most of the food supply. The

Federal Food, Drug, and Cosmetic Act establishes the standard for food
Page 8 GAO-02-566 Genetically Modified Foods

safety as food being in an unadulterated condition.5 FDA established its

basic policy regarding the review of GM foods in its 1992 Policy on Foods

Derived from New Plant Varieties. According to this policy, FDA relies on

companies developing GM foods to voluntarily notify the agency before

marketing the foods.6

 Notification leads to a two-part consultation process

between the agency and the company that initially involves discussions of

relevant safety issues and subsequently the company’s submission of a

safety assessment report containing test data on the food in question. At

the end of the consultation, FDA evaluates the data and may send a letter

to the company stating that the agency has no further questions, indicating

in effect that it sees no reason to prevent the company from marketing the

GM food. In 1997, FDA supplemented its 1992 Policy with the current

Guidance on Consultation Procedures, clarifying procedures for the

initial and final consultations.

In January 2001, FDA issued a proposed rule in the Federal Register that

provides further information on these procedures and, more importantly,

would require pre-market notification by companies. Among the reasons

that FDA cited for this change are concerns expressed by consumers and

public interest groups about the limited transparency and voluntary nature

of the current process. FDA also pointed to the growing power of

biotechnology to create potentially more complex safety issues that could

require more stringent regulatory evaluations. FDA, tentatively, expects to

finalize this rule as early as fiscal year 2003.

 5

 21 U.S.C. § 342. A food is deemed adulterated if, among other things, it contains an added

poisonous or deleterious substance that may render the food injurious to health or if it

contains an unapproved food additive.

6

 FDA has not routinely evaluated the safety of foods derived from new plant varieties that

were produced by traditional breeding. FDA has generally not evaluated these foods

because plant breeders have longstanding established and reliable practices for ensuring

food safety.
Page 9 GAO-02-566 Genetically Modified Foods

All foods, including those from GM plants, pose the same types of inherent

risks to human health: they can cause allergic or toxic reactions, or they

can block the absorption of nutrients. Although some foods from GM

plants have contained allergens, toxins, and antinutrients, scientists agree

that the levels of these compounds have been comparable to those found

in the foods’ conventional counterparts. To reach such a finding, each GM

food is evaluated using a regimen of tests. This regimen begins with tests

on the source of the gene being transferred, proceeds to tests examining

the similarity of the GM food to conventional varieties with known

allergens, toxins, and antinutrients, and may include tests on the safety of

the modified protein from the GM food in simulated digestive fluids. At

every phase, test results are compared to the risk levels found in the food’s

conventional counterpart. If the risk levels are within the same range as

those for the conventional food, the GM food is considered as safe as its

conventional counterpart. Despite the limitations of individual tests,

several experts agree that this regimen of tests has been adequate for

ensuring the safety of GM foods.

According to reports from the Organization for Economic Cooperation and

Development, the Codex Alimentarius,7

 and FDA, foods from GM plants

pose three types of risk to human health: they can potentially contain

allergens, toxins, or antinutrients. These risks are not unique to GM foods.

People have consumed foods containing allergens, toxins, and

antinutrients throughout human history. The small percentage of the

population with food allergies (1-2 percent of adults and 6-8 percent of

children) tries to prevent allergic reactions by avoiding offending foods.

Additionally, people commonly consume toxic substances in foods, but

they usually do so at levels that are considered safe. People also frequently

consume foods containing antinutrients, such as certain proteins that

inhibit the digestion of nutrients in the intestinal tract, but common food

preparation techniques, such as cooking, break down the antinutrients.

Moreover, consumption of a varied diet, in which a person is exposed to

multiple nutrient sources, mitigates the risk of malnutrition from

antinutrients, according to FDA officials and various academicians.

 7

 Codex Alimentarius is the joint food standards program for the United Nations’ Food and

Agriculture Organization and the World Health Organization that was established in 1962.

Its objectives are to help protect the health of consumers and facilitate trade through the

establishment of international food standards, codes of practice, and other guidelines.

GM Foods Share the

Same Types of Health

Risks as Conventional

Foods and Are

Evaluated by Tests

That Appear Adequate

All Foods Share the Same

Three Risks, Which Are

Evaluated in GM Foods
Page 10 GAO-02-566 Genetically Modified Foods

Because conventional foods contain allergens, toxins, and antinutrients,

scientists recognize that food cannot be guaranteed to pose zero risk. The

primary concern with the genetic modification of food with respect to

human health, state industry officials, is the potential for unintentional

introduction of a new allergen, an enhanced toxin, or an enhanced

antinutrient in an otherwise safe food. For this reason, developers

evaluate GM foods to determine if they are as safe as their conventional

counterparts.

An allergic reaction is an abnormal response of the body’s immune system

to an otherwise safe food. Some reactions are life threatening, such as

anaphylactic shock.8

 To avoid introducing or enhancing an allergen in an

otherwise safe food, the biotech food industry evaluates GM foods to

determine whether they are “as safe as” their natural counterparts. For

example, in 1996 FDA reviewed the safety assessment for a GM soybean

plant that can produce healthier soybean oil. As part of a standard safety

assessment, the GM soybean was evaluated to see if it was as safe as a

conventional soybean. Although soybeans are a common food allergen and

the GM soybean remained allergenic, the results showed no significant

difference between its allergenicity and that of conventional soybeans.

Specifically, serums (blood) from individuals allergic to the GM soybean

showed the same reactions to conventional soybeans.

A toxic reaction in humans is a response to a poisonous substance. Unlike

allergic reactions, all humans are subject to toxic reactions. Scientists

involved in developing a GM food aim to ensure that the level of toxicity in

the food does not exceed the level in the food’s conventional counterpart.

If a GM food has toxic components outside the natural range of its

conventional counterpart, the GM food is not acceptable.

To date, GM foods have proven to be no different from their conventional

counterparts with respect to toxicity. In fact, in some cases there is more

confidence in the safety of GM foods because naturally occurring toxins

that are disregarded in conventional foods are measured in the pre-market

safety assessments of GM foods. For example, a naturally occurring toxin

in tomatoes, known as tomatine, was largely ignored until a company in

the early 1990s developed a GM tomato. FDA and the company considered

it important to measure potential changes in tomatine. Through an

analysis of conventional tomatoes, they showed that the levels of

 8

 Anaphylactic shock is a severe allergic reaction that can lead to death.

Allergic Reactions

Toxic Reactions
Page 11 GAO-02-566 Genetically Modified Foods

tomatine, as well as other similar toxins in the GM tomato, were within the

range of its conventional counterpart.

Antinutrients are naturally occurring compounds that interfere with

absorption of important nutrients in digestion. If a GM food contains

antinutrients, scientists measure the levels and compare them to the range

of levels in the food’s conventional counterpart. If the levels are similar,

scientists usually conclude that the GM food is as safe as its conventional

counterpart. For example, in 1995 a company submitted to FDA a safety

assessment for GM canola. The genetic modification altered the fatty acid

composition of canola oil. To minimize the possibility that an unintended

antinutrient effect had rendered the oil unsafe, the company compared the

antinutrient composition of its product to that of conventional canola. The

company found that the level of antinutrients in its canola did not exceed

the levels in conventional canola.

To ensure that GM foods do not have decreased nutritional value,

scientists also measure the nutrient composition, or “nutrition profile,” of

these foods. The nutrient profile depends on the food, but it often includes

amino acids, oils, fatty acids, and vitamins. In the example previously

discussed, the company also presented data on the nutrient profile of the

GM canola and concluded that the significant nutrients were within the

range of those in conventional canola.

Companies that may wish to submit new GM foods for FDA evaluation

perform a regimen of tests to obtain safety data on these foods. FDA’s

1992 policy on safety assessments of GM foods describes the data the

agency recommends it receive to evaluate these foods. Figure 2 provides

an example of the regimen of tests. This regimen usually includes an

analysis of

• the source of the transferred genetic material, specifically whether the

source of the transferred gene has a history of causing allergic or toxic

reactions or containing antinutrients;

• the degree of similarity between the amino acid9 sequences in the newly

introduced proteins of the GM food and the amino acid sequences in

known allergens, toxins, and antinutrients;

 9

 Amino acids are the “building blocks” of the proteins in the body. Besides building cells

and repairing tissue, the proteins form antibodies to combat invading bacteria and viruses,

build DNA and RNA, and carry oxygen throughout the body.

Antinutrient Effects

Companies Use a Regimen

of Tests to Ensure GM

Food Safety
Page 12 GAO-02-566 Genetically Modified Foods

• data on in vitro digestibility (i.e., how readily the proteins break down in

simulated digestive fluids)

• the comparative severity of individual allergic reactions to the GM product

and its conventional counterpart as measured through blood (serum)

screening—when the conventional counterpart is known to elicit allergic

reactions or allergenicity concerns remain; and

• data on any changes in nutrient substances, such as vitamins, proteins,

fats, fiber, starches, sugars, or minerals due to genetic modification.

Occasionally, the regimen of tests also includes animal studies for toxicity.

As shown in figure 2, the tests provide evidence at key decision points to

direct which tests are subsequently performed. Tests on the source of the

newly expressed protein, amino acid sequence similarity, and digestibility

are typical for both allergenicity and toxicity assessments, while serum

screening is used only for allergenicity assessment. Also, while the

complete regimen is not necessary for every GM food safety assessment,

companies often perform extra tests in the regimen to corroborate the

results of previous tests.
Page 13 GAO-02-566 Genetically Modified Foods

Figure 2: Example of the Regimen of Tests Used for Safety Assessments of GM

Foods

Source: GAO’s analysis of FDA documents.

Notes:

Figure 2 represents typical tests undertaken by a company in the safety assessment of a GM food.

The figure is not meant to be a comprehensive illustration that is used in every safety assessment.

Antinutrients are tested as a subset of toxicity. In addition, they are often measured with a simple

nutrition/composition profile.

If a company transfers genetic material from an allergenic source and undertakes serum screening

tests, it does not have to go though serum screening again if in vitro digestibility tests uncover a

similarity to an allergen. At such a point, it would be assessed by amino acid sequence similarity and

in vitro digestibility tests for potential toxicity.
Page 14 GAO-02-566 Genetically Modified Foods

If a company reaches the “Stop (or consult)” decision point, then there are food safety concerns about

allergenicity or toxicity issues. At this point, FDA’s 1992 policy statement says the company should

consult with FDA. However, this usually means the company will discontinue development of the GM

product because of allergenicity or toxicity concerns. A company may consult with FDA if there were

changes in the nutrition/composition profile that were intended.

Animal studies are occasionally conducted as an extra test for potential toxicity.

Using allergenicity as an example, if a company transfers a gene from a

source that is not an allergen, the company evaluates the amino acid

sequence of the GM protein. If the GM protein has an amino acid sequence

similar to that of known allergens, the company initiates further, more

specific allergenicity testing. The company would undertake in vitro

digestibility tests to see if the GM protein was broken down in simulated

digestive fluids. If there were any concerns about the speed with which the

GM protein was broken down, the company would use serum-screening

tests to support or refute the results of the digestibility tests when serums

are available. If the serum screening yields results showing that the GM

protein does not react with antibodies in serum, then the company

concludes the GM protein does not raise allergenicity concerns. The

results from this regimen of tests provide the weight of evidence necessary

to determine the safety of a GM food.

Examining the source of the transferred genetic material is the starting

point in the regimen of tests for safety assessments. According to a

scientist from a biotechnology company, two principles of allergenicity

assessment underlying the regimen of tests contribute to adequate safety

assessments: scientists (1) avoid transferring known allergenic proteins

and (2) assume all genes transferred from allergenic sources create new

food allergies until proven otherwise. If the source contains a common

allergen or toxin, industry scientists must prove that the allergenic or toxic

components have not been transferred. However, as a practical matter,

biotechnology companies repeatedly state that if the conventional food is

considered a major food allergen,10 they will not transfer genes from that

source. Accordingly, experts from FDA and the biotechnology industry

agree that the probability of introducing a new allergen, enhancing a toxin,

or enhancing an antinutrient is very small.

The next step involves a comparison between the amino acid sequences of

the transferred proteins of the GM food plant and those of known

allergens, toxins, or antinutrients. If scientists detect an amino acid

 10 Major food allergens are dairy milk, eggs, fish, peanuts, shellfish, soybeans, tree nuts, and

wheat.

Source of the Transferred

Genetic Material

Amino Acid Sequence

Similarity
Page 15 GAO-02-566 Genetically Modified Foods

sequence in a GM food identical or similar to one in an allergen, toxin, or

antinutrient, then there is a likelihood that the GM food poses a health

risk. Overall, sequence similarity tests are very useful in eliminating areas

of concern and revealing areas for further evaluation.

In vitro digestibility tests are a primary component of all GM food safety

assessments. These tests analyze the breakdown of a GM protein in

simulated human digestive or gastric fluids. The quick breakdown of a GM

protein in these fluids indicates a very high likelihood that the protein is

not allergenic or toxic. Safe dietary proteins are almost always rapidly

digested, while allergens and toxins are not.

If a gene raises allergenicity concerns, a company can include serum

screening tests in its safety assessment of a GM food. Serum screening is

used only for allergenicity assessment. Serum screening involves

evaluating the reactivity of antibodies in the blood of individuals with

known allergies to the plant that was the source of the transferred gene.

Antibody reactions suggest the presence of an allergenic protein. Serum

screening tests are valuable because they can expose allergens whose

presence was only suggested in amino acid sequence similarity tests.11

Since there are neither abundant, appropriate stored serums nor many

suitable human test subjects, these tests cannot always be used.

Scientists also create a nutritional and compositional12 profile of the GM

food to assess whether any unexpected changes in nutrients, vitamins,

proteins, fibers, starches, sugars, minerals, or fats have occurred as a

result of the genetic modification. While changes in these substances do

not pose a risk of allergenicity, toxicity, or antinutrient effects to human

health, creating a nutritional and compositional profile further ensures

that the GM food is comparable to its conventional counterpart.

 11 Clinical tests to corroborate the results of serum screening include skin prick tests and

double-blind placebo-control food challenges. Skin prick tests involve scratching the skin

of individuals with food allergies to determine if the new GM product elicits allergic skin

reactions. Double-blind placebo-control food challenges aim to eliminate possible

psychosomatic reactions of allergic individuals by giving them either a test product or a

control product.

12 “Compositional” refers to the concentration of nutrients and other key substances in a

plant, since the concentration of nutrients—not just the presence—is important in

assessing unexpected changes.

Digestibility Tests

Serum Screening

Nutritional and Compositional

Profile
Page 16 GAO-02-566 Genetically Modified Foods

Biotechnology companies occasionally use animal studies to confirm the

results of prior toxicity tests. For the most part, these studies have

involved feeding extraordinarily high doses of the modified protein from a

GM food to mice. The doses of the modified protein are often hundreds to

thousands of times higher than the likely dose from human diets.

Scientists perform these studies to determine if there are any toxic

concerns from the GM food.

Animal studies also have the potential to predict allergenicity in humans,

although scientists have not yet identified an animal that suffers from

allergic reactions the same way that humans do. The brown Norway rat

has provided the closest approximation to human allergic reactions to

several major food allergens. However, animal models—as predictors of

allergenic responses in humans—are not scientifically accepted at this

time.

Biotechnology experts whom we contacted from a consumer group, FDA,

academic institutions, research institutions, the European Union and

biotechnology companies said that the current regimen of tests has been

adequate for assessing the safety of GM foods.13 All but one expert

considered the regimen of tests to be “good” or “very good” for ensuring

the safety of GM foods for public consumption, and the remaining expert

viewed the tests as “fair.” While the experts noted that individual tests

have limitations, most experts agreed that results from the regimen of

tests provide the weight of evidence needed for scientists to make an

accurate assessment of risk. 14

A distinction made by an academician and regulatory officials is that the

available tests do not guarantee absolute safety of GM foods, but

comparable safety. There is no assurance that even conventional foods are

completely safe, since some people suffer from allergic reactions, and

conventional foods can contain toxins and antinutrients. Because they

 13 Some consumer groups, as well as some scientists from the European Union, have

questioned the ethical or cultural appropriateness of genetically modifying foods.

14 According to FDA officials, they are aware of only one example—involving the Brazil

nut—of GM food development where an allergen-producing gene was transferred. In this

case, the regimen of tests used in safety assessments for GM foods successfully identified

the presence of the allergen-producing gene before the product was ever submitted for

FDA review. The company subsequently discontinued research, development, and testing

of the food.

Animal Studies

According to Experts, GM

Food Safety Tests Have

Been Adequate
Page 17 GAO-02-566 Genetically Modified Foods

have been consumed for many years, though, conventional foods are used

as the standard for comparison in assessing the safety of GM foods, and

experts note that the available tests are capable of making this

comparison.

While experts agree that the available regimen of tests is adequate for

safety assessments, there are limitations to individual tests. For example,

there are limitations to the acceptability of amino acid sequence similarity

test results, in part because there is not agreement on what level of amino

acid similarity indicates a likelihood of allergenicity and, therefore, the

need for additional testing. Industry scientists assert that as long as amino

acid sequences in a protein are less than 50 percent identical to those in

known allergens, then the protein should not raise concerns. On the other

hand, a scientist associated with a consumer group, as well as a report

from the United Nations’ Food and Agriculture Organization, believe a

more conservative level, such as less than 35 percent identical, is

appropriate. Thus, experts from industry and consumer groups suggest

that reaching agreement on this parameter would increase the consistency

with which these tests are applied.

In vitro digestibility tests also have limitations because they can yield

inaccurate results when performed under inappropriate parameters, such

as improper digestive fluid pH levels. 15 If a GM food protein is tested at a

pH level representative of intestine digestion, yet the protein in real life is

digested at a different pH level in the stomach, then the results of the test

are not valid for reaching conclusions on the GM food’s likely effect in

humans. FDA officials note that there is growing acceptance that the

proper pH level for digestive stability tests is the pH level of the human

stomach. As a result, experts from industry and consumer groups suggest

that reaching agreement on the parameters in digestive stability tests—

such as proper pH ranges—would help ensure that they are performed

properly.

Information on acceptable testing procedures (including parameters) is

available from a variety of sources. For instance, AOAC International16

documents standardized tests and test procedures, such as test procedures

for examining nutrient levels in a GM food. Other groups, such as the

American Oil Chemists’ Society and the American Association of Cereal

 15 The pH level indicates the degree of acidity or alkalinity.

16 This organization was formerly known as the Association of Official Analytical Chemists.
Page 18 GAO-02-566 Genetically Modified Foods

Chemists also have information on official tests and test procedures.

However, there is no centralized source of information on these

procedures. Although FDA maintains a Web site with guidance for

consultations, the Web site does not contain information about acceptable

testing procedures.

According to FDA, it has the necessary controls to ensure it obtains the

safety data needed for its GM food evaluations. In examining a selection of

submissions, we found that companies adhered to FDA’s recommended

procedures for the type of data to be submitted. However, biotechnology

experts state that the agency’s overall evaluation process could be

enhanced by randomly verifying the test data that companies provide and

by increasing the transparency of the evaluation process—including more

clearly communicating the scientific rationale for the agency’s final

decision on GM food safety assessments. FDA believes that making these

changes would enhance the public’s confidence in the agency’s evaluation

process.

According to agency officials, FDA has several management practices that,

in aggregate, constitute internal controls.17 The officials state that these

practices effectively ensure FDA obtains the data necessary for evaluating

the potential risks of GM foods. These practices include:

• communicating clearly what safety data are important to FDA’s

evaluations of GM food safety,

• having teams of FDA experts representing diverse disciplines perform the

evaluations, and

• tailoring the level of evaluation to match the degree of each GM food’s

novelty.

One key indication of the effectiveness of these practices is FDA’s ability

to determine when data are inadequate and to specify the additional data

important to a complete evaluation. In the cases we examined when the

 17 Standards for Internal Control in the Federal Government (GAO/AIMD-00-21.3.1,

Washington, D. C.: November 1999) defines internal controls as an integral component of

an organization’s management that provides reasonable assurance that effectiveness and

efficiency of operations and compliance with applicable laws and regulations are being

achieved.

FDA Believes That It

Obtains Necessary

Safety Data for GM

Food Evaluations, but

FDA’s Overall

Evaluation Process

Could Be Enhanced

FDA Believes Its

Management Practices Are

Generally Effective in

Ensuring It Obtains the

Data Necessary for Its

GM Food Evaluations
Page 19 GAO-02-566 Genetically Modified Foods

company’s initial submission of data was insufficient, FDA was able to

specify and obtain additional data from the company.

For a GM food, the evaluation process, known as a consultation, generally

lasts between 18 months and 3 years, according to FDA officials. In what

FDA calls the “initial” phase of the consultation, FDA and company

officials discuss what safety data will be needed for a GM food

submission. In the next or “final” phase, the company prepares a detailed

report summarizing this data and submits it to FDA. After receiving and

evaluating the report, FDA officials prepare a “memo to file.” This memo is

the formal document in which FDA summarizes and evaluates everything

the company has submitted. Consultation is complete when FDA

determines that it has no further questions regarding the safety of the GM

food and informs the company of this conclusion in a letter signed by the

director of the FDA’s Office of Food Additive Safety. Receiving such a

letter is generally helpful to companies in marketing their product.

In FDA’s 1992 policy statement and its subsequent 1997 guidance, the

agency clearly states what information companies should submit for FDA

to assess the safety of GM foods. Specifically, the 1992 statement includes

several risk assessment decision trees that provide a step-by-step

approach to testing. FDA recommends that companies follow this

approach in their assessments of GM foods. Using this approach,

companies must show whether any allergens, toxins, or antinutrients have

been introduced or enhanced. FDA’s 1997 guidance builds upon the 1992

policy statement by describing in more detail the process, procedures, and

time frames pertaining to the initial and final consultations.

FDA officials stated that the principles embodied in their 1992 policy

statement guided the consultations for the 50 GM foods evaluated so far

and that companies have closely adhered to these principles. In examining

five submissions,18 we found that companies adhered closely to the 1992

policy statement. For example, a 1996 submission for a GM soybean19

shows step-by-step adherence to the allergenicity decision tree established

 18 The five submissions reviewed are representative of the three main types of GM plants

evaluated as of April 2002: pest-resistant plants, herbicide-tolerant plants, and plants having

modified oils. Specifically, we reviewed submissions for a pest-resistant corn; an herbicidetolerant sugar beet and soybean; and high oleic-acid soybean oil and laurate canola oil.

19 This GM soybean was engineered to contain a substantially higher percentage of oleic

acid.

FDA Guidance Describes

Safety Data Needed
Page 20 GAO-02-566 Genetically Modified Foods

in the 1992 policy statement. Extensive data submitted by the company

enabled FDA to conclude that it had no unanswered questions about the

safety of the soybean. Later submissions involving an herbicide-tolerant

sugar beet and pest-resistant corn also showed a close adherence to the

1992 policy statement.

Evaluations of GM food safety submissions must include concurrence

from every member of a highly qualified team known as the Biotechnology

Evaluation Team.20 The 1997 guidance states that the evaluation teams

generally will be composed of a consumer safety officer (who serves as

the project manager), molecular biologist, chemist, environmental

scientist, toxicologist, and nutritionist. The guidance also states that the

evaluation teams may be supplemented with additional expertise on a

case-by-case basis. According to agency officials, these experts are

qualified to perform what is effectively a peer review21 of each submission.

Consumer safety officers, who generally have doctorates in relevant

disciplines, including molecular biology, cell biology, or immunology,

chair the teams. According to FDA officials, in addition to their scientific

credentials, the consumer safety officers know what is needed for the

administrative record for each submission. This knowledge encompasses

the laws and regulations, such as the Federal Food, Drug, and Cosmetic

Act, as well as specific pertinent procedures, such as FDA’s 1992 policy

statement. According to FDA officials, the combination of scientific and

administrative expertise makes the consumer safety officers effective

leaders of the teams.

FDA officials indicated that each member of an evaluation team reviews

the entire file for a given GM food submission. These officials viewed this

as another strength of the evaluation process. In particular, they stressed

that the final evaluation is not a “piecemeal” evaluation in which, for

example, the toxicologist receives only the toxicological data to review.

Rather, each team member receives and examines all the data that the

company has submitted. Further, team members must document in writing

the results of all key interactions with a company throughout the course of

 20 Within FDA, the Center for Food Safety and Applied Nutrition oversees the

Biotechnology Evaluation Teams for consultations on human food. FDA’s Center for

Veterinary Medicine oversees teams for consultations involving GM animal feed.

21 Peer review is the critical evaluation of data, analysis, or documents by professional

colleagues. It is the traditional method of quality control in science.

GM Food Evaluations Are

Conducted by Multidisciplinary

Teams
Page 21 GAO-02-566 Genetically Modified Foods

the evaluation; this documentation is then available for the whole team to

evaluate. Lastly, the entire team must concur with the final draft of the

memo to file, which is usually prepared by the consumer safety officer.

In summary, FDA officials told us that the expertise of the Biotechnology

Evaluation Team members coupled with the multiple reviews of

information enables the team to adequately evaluate safety assessments

and determine if and when more data is needed.

According to agency officials, FDA’s practice of varying its level of

evaluation based on the degree of novelty of the GM food submission

allows it to devote resources where they are most needed, thus assuring

that Biotechnology Evaluation Teams have time to obtain necessary safety

data. FDA’s evaluation of one company’s GM tomato provides an example

of a detailed evaluation of a novel submission that went through both the

initial and final consultations. Specifically, the Biotechnology Evaluation

Team requested extensive detail from the company on the modification of

the tomato, which involved the insertion of one gene to delay ripening and

another gene to show that this trait was transferred. FDA’s documentation

of its evaluation presented background information on these

modifications, a point-by-point evaluation of the company’s food safety

assessment, and FDA’s conclusion that the tomato was not significantly

different from conventional tomatoes.

By contrast, FDA officials stated that evaluations of company submissions

for GM foods similar to GM foods previously evaluated by the agency

(such as a virus-resistant squash and various herbicide-tolerant corns)

required fewer agency resources because these submissions skipped the

initial consultation and proceeded to the final consultation. In fact, FDA’s

1997 guidance states that a company might skip the initial consultation

and go directly to the final consultation by submitting its final report.

According to FDA officials, this skipping often occurs when a company

has made multiple submissions for similar GM foods involving only minor

variations from one case to the next. Having once gone through the full

consultation process for a specific genetic modification, such a company

is familiar with the kinds of safety information that FDA expects and thus

can proceed directly to preparing a final report for similar cases. FDA’s

documentation of its evaluation of such submissions can be less detailed.

According to FDA officials, in cases in which the agency determines that

the data submitted by a company are insufficient, the company has always

cooperated with FDA by performing additional tests and/or submitting the

data needed. FDA officials described three types of situations where they

FDA Tailors Its Evaluation to

Match the Degree of Novelty in

Each Submission

FDA Believes It Obtains

Complete, Consistent Data
Page 22 GAO-02-566 Genetically Modified Foods

have requested additional data and companies have responded: (1) the

absence of a reliable or “validated” method for performing a test; (2)

reliance on a prevailing scientific “assumption” that, when tested at FDA’s

request, was proven incorrect; and (3) inconsistent or incomplete data in

the final reports.

The first situation involved the lack of a reliable method for testing

tomatine, a naturally occurring toxin in tomatoes. The company that

encountered this problem was inexperienced in analytical chemistry, and

the laboratory with which it was working did not have an acceptable

method. In evaluating the measurements of tomatine submitted by the

company, FDA officials found these data unconvincing. As a result, FDA

officials suggested that the company find a more appropriate method. In

response, the company obtained a suitable method from another

laboratory and later provided FDA with new data that the agency found

convincing.

The second situation is illustrated by FDA’s evaluation of a GM tomato

altered to delay ripening. In this submission, the company assumed that

only a certain segment of DNA was transferred. FDA asked the company

to prove the accuracy of this assumption. Testing by the company then

revealed that additional DNA had been transferred. This discovery led to

more thorough analysis of the genetic modifications, including additional

efforts to ensure that the transfer of extra DNA did not cause unintended

changes.

In the third situation, FDA noted discrepancies in the data in final reports

involving GM cotton, rice, and canola and requested the relevant

companies to correct the information, which they did.

Biotechnology experts state, and FDA agrees, that its overall evaluation

process for assessing the safety of GM foods could be enhanced by

• verifying the GM food-related test data that companies provide, and

• increasing the transparency of the evaluation process.

Biotechnology experts from consumer groups and academia state that

FDA’s evaluation process could be enhanced if the agency validated

companies’ test results on proposed GM products by reviewing raw data

(e.g., the actual, unverified test results). Further, FDA believes that

occasional reviews of the raw data developed by companies would further

enhance the credibility of, and public confidence in, the overall safety data

FDA Evaluations of GM

Foods Could be Enhanced

FDA Could Validate Company

Safety Data
Page 23 GAO-02-566 Genetically Modified Foods

that companies submit. In addition, we believe occasional data verification

by a federal agency is necessary to (1) identify the risk of the agency’s

receiving faulty data from external sources and (2) ensure that no one

agent is allowed to control every key aspect of a safety assessment.22

FDA officials stated that they do not believe it is necessary for the agency

to routinely review raw data for two reasons. First, the risk of incurring

criminal penalties for deliberately submitting false data to FDA provides a

significant degree of deterrence. Second, FDA’s evaluation process

constitutes a peer review of the safety data that will generally detect any

problems.23 However, these officials added that an occasional review of

raw data, performed on a random basis, would further help ensure the

reliability of FDA’s evaluation of these foods, and thus enhance public

confidence in the agency’s evaluation process.

Officials from a major biotech company described three types of GM food

safety data developed for each submission and available for FDA’s review:

(1) raw data, (2) refinements and comprehensive interpretations of the

raw data, and (3) summaries of these interpretations. According to these

officials, FDA has reviewed the summaries, and in some instances the

comprehensive interpretations, but has not reviewed the raw data. These

officials note, and FDA officials concur, that nothing prevents FDA from

reviewing these raw data. In general, these raw data are readily available

from companies. The company officials also note that EPA has

occasionally reviewed raw data in its safety assessments of GM plants

regarding their environmental effects. Moreover, FDA officials stated the

agency reviews raw data in its safety assessments of new drug

applications.

Experts from consumer groups and academia have stated that the

transparency of the agency’s evaluation process for GM foods could be

enhanced if FDA described more clearly the scientific rationale for its

safety decisions in its memo to file. FDA agrees. Guidelines issued by the

 22 U.S. General Accounting Office, Internal Control Management and Evaluation Tool

GAO-01-1008G (Washington, D.C.: August 2001).

23 Among other factors not directly linked with internal controls, FDA officials pointed out

that the majority of requests for access to GM food submissions through the Freedom of

Information Act come from competitors, who, according to these officials, would likewise

be quick to detect a problem with the data. Scientists, consumer groups, and other

interested parties have also asked for access to these submissions. However, the data

reviewed by these groups does not include the raw data.

FDA Could Increase the

Transparency of Its Evaluations
Page 24 GAO-02-566 Genetically Modified Foods

Office of Management and Budget on the quality of information

disseminated by federal agencies state that transparency is important in

reviews of technical information and that these reviews should be

conducted in an open and rigorous manner.24 Yet critics have stated that

FDA’s current memos to file do not adequately communicate the scientific

rationale for the decisions. Some consumer groups have pointed out the

brevity of some of the memos and described them as “perfunctory”

summaries of company data that provide little or no insight into FDA’s

evaluation of the data. Likewise, the Council for Agricultural and Science

Technology, a group of universities and companies established to provide

a more scientific basis for analyzing and prioritizing agricultural issues,

stated that FDA does not adequately clarify in its memos to file the basis

for its decisions on GM food submissions. Our review of memos to file for

the 50 GM food products evaluated by FDA as of April 2002 confirms that

these memos do not clearly explain the scientific rationale for FDA’s

decisions.

In response to these concerns, FDA officials note that the memos to file

had originally been created for FDA’s internal use rather than as public

documents. Thus, they were not designed to provide detailed rationales of

FDA’s decisions on GM food submissions. In addition, FDA officials said

that some memos are brief because they record decisions on GM foods

that are very similar to previously evaluated GM foods. However, FDA

officials acknowledge that FDA could do more to inform the public of the

basis for their decisions. For example, FDA could include comments in the

memos to file that better reflected the context of the evaluation (for

instance, its similarity to previous evaluations), the adequacy of the tests

performed by the company, and the level of evaluation provided by FDA.

For those memos to file on submissions for GM foods that are similar to

GM foods previously evaluated, FDA could make reference to earlier,

similar submissions having a more detailed memo to file.

 24 Guidelines for Ensuring and Maximizing the Quality, Utility, and Integrity of

Information Disseminated by Federal Agencies (Office of Management and Budget,

Washington, D. C.: January 2002).
Page 25 GAO-02-566 Genetically Modified Foods

Scientists expect future GM foods to include modifications of plant

composition that may enhance the nutritional value of these foods but may

also increase the difficulty of assessing their safety. While current tests

have been adequate for evaluating the small number of relatively simple

compositional changes made so far, some scientists believe that new

testing technologies under development may be needed to assess the

safety of these more complex GM foods. Scientists have diverging views

on the potential role of these new technologies: some view them as a

useful supplement to existing tests, while others view them as a new, more

comprehensive way to assess the safety of all changes in GM foods.

However, the lack of technical standards for these new technologies and

proof of their reliability prevents their current use.

Until now, most genetic modifications of plants have been aimed at

increasing or protecting crop yield. These modifications have generally

focused on the portions of plants, such as cornstalks, that are not

consumed by humans. However, many scientists believe that the current

wave of yield-related modifications will expand to include a new wave of

genetic modifications involving compositional changes in the foods to

enhance their nutritional value. For example, “golden” rice is a GM food

under development that was modified to contain beta-carotene, a

precursor of vitamin A.25 Golden rice may help to reduce the incidence of

blindness in countries where rice is a dietary staple and malnutrition is

common. Also under development are compositional changes that will

increase the levels of vitamin E in foods. Plants are the primary source of

this vitamin, which is believed to have cancer-preventing properties, but

plants generally contain it in relatively low concentrations. A gene

controlling vitamin E production was transferred recently to a member of

the mustard plant family, which subsequently exhibited a nine-fold

increase in this vitamin. According to a recent report,26 incorporation of

this gene into major crops such as soybeans, canola, and corn is probably

not far in the future.

In addition to increasing nutrients in GM foods, scientists are working to

reduce the presence of allergens, toxins, and antinutrients. For example,

 25 The human body converts beta-carotene into vitamin A if the body is deficient in

vitamin A.

26 Pew Initiative on Food and Biotechnology, Harvest on the Horizon: Future Uses of

Agricultural Biotechnology, Washington, D. C., September 2001.

Future Changes in GM

Foods May Alter Their

Composition and

Require New Testing

Technologies for

Assessing Safety

Experts Foresee

Compositional Changes
Page 26 GAO-02-566 Genetically Modified Foods

scientists have genetically modified wheat, one of the major allergenic

foods, to stimulate a gene that diminishes wheat’s allergenic properties.

Scientists are also seeking ways to reduce toxic substances, such as

alkaloids in potatoes, by inserting genes that block their production.

Preliminary findings have indicated that GM potatoes produced fewer of

these alkaloids. Likewise, some plants, especially cereals and legumes, are

nutritious foods but contain varying amounts of antinutrients. Genetic

modifications are being explored to reduce these antinutrients.

If adopted, FDA’s proposed rulemaking mandating the testing of all GM

foods prior to commercialization will represent a timely response to this

new wave of GM foods. For example, the preamble to the rule notes that

some of the new ingredients in GM foods will significantly differ from

ingredients that have a history of safe use. The rule also notes that

products derived from this advanced biotechnology will present more

complex safety and regulatory issues than those seen to date. The

proposed rule concludes that nontraditional strategies for evaluating food

safety will become the norm as the use of biotechnology expands. FDA

officials explained that “nontraditional strategies” could include new

technologies under development such as those described in the next

section.

Some scientists believe that testing technologies being developed but not

yet widely applied to GM foods may be useful in assessing the safety of

compositional changes and detecting unintended effects.27 In contrast to

current tests that examine the human health effects of transferred genes

and other relevant components on a highly selective basis, the new

technologies will examine essentially all of the components—such as

DNA, proteins, and metabolites28—in conventional and GM plants

simultaneously to detect any differences. These new technologies include

 27 Unintended effects involve the accidental creation of an allergen, enhancement of a toxin

or antinutrient, or unintentional alteration of the nutritional profile of a food. Unintended

effects can also involve changes in crop yield and growth rates.

28 Metabolites are small molecules in living cells. These small molecules include vitamins

(with potential benefits for human health) and alkaloids (a major source of toxicity in

plants). Their “smallness” is defined in contrast to generally much larger molecules such as

proteins.

New Testing Technologies

May Be Useful in

Addressing Compositional

Changes
Page 27 GAO-02-566 Genetically Modified Foods

• gene chips that use thousands of droplets of DNA on glass chips to

identify gene sequences and determine the expression level or abundance

of the genes;

• proteomics which can analyze up to 100,000 proteins simultaneously; and

• metabolic profiling that can analyze the 2,000 to 3,000 metabolites in

people and 3,000 to 5,000 metabolites in plants.

In essence, these new technologies combine huge increases in automated

computing power with traditional testing technologies to identify

differences between conventional and GM foods in ways that would have

been impossible even a few years ago.

A university scientist further explained the contrast between the current

and new technologies by noting that traditional tests focus on known

toxins and nutrients in a “targeted” approach, whereas new technologies

use a “non-targeted” approach to increase the chance of detecting

unintended effects of genetic modifications such as the creation of a toxin.

According to this scientist, the latter approach has particular applicability

to second-generation plants with extensive modifications, which may be

more likely to have unintended effects. For example, a scientist with a

consumer group stated that the new technologies may be useful in

detecting unintended effects that traditional tests, such as those for

digestibility, are not likely to identify. Other scientists expressed the need

for caution and additional information to determine the potential role of

these new technologies.

Gene chips consist of grids of thousands of droplets of DNA on small glass

surfaces. The chip-based DNA can bind with the DNA or RNA being tested

to determine which genes are present or are being activated. Used in

conjunction with DNA and RNA databases under development at various

universities and other research institutions, this testing technique has

yielded insights into areas such as the ripening process of tomatoes and its

relation to toxins and nutrients. The major advantage of gene chips over

conventional testing techniques is that they allow small-scale analysis of

thousands of genes at the same time in a precise and quantitative manner.

According to a university scientist, researchers are determining the extent

to which this technology may be effective in assessing GM food safety.

Proteomics is a biotechnology technique used to identify many proteins

simultaneously in a given organism. Using chemical analyses and

computers, proteomics goes beyond plant studies focusing on DNA and

RNA, which do not provide information on the actual creation of the

proteins. Proteomics has been introduced successfully in medical

Gene Chips

Proteomics
Page 28 GAO-02-566 Genetically Modified Foods

disciplines such as oncology, where it has helped to identify proteins

associated with cancer, but it has not yet been used to evaluate the safety

of GM foods for two reasons. First, there are a large number of proteins

that need to be analyzed in any given plant. Second, the function of

proteins in a plant may change depending on their interaction with

different cells and tissues. According to a university scientist, researchers

are working to expedite the analysis of proteins in plants.

Metabolic profiling uses chemical analyses and computers to obtain a

simultaneous, detailed look at all of the small molecules (metabolites) in a

given GM plant to determine the extent to which these molecules have

changed in comparison to a conventional plant, if at all. According to

scientists at one company involved in developing metabolic profiling, this

technique can determine whether a specific, intended change in a small

molecule has been achieved. It can also identify any unintended changes

in other small molecules—changes such as increased alkaloids, which are

a major source of toxicity in plants. If the profiling finds no unintended

changes in these molecules, then it offers a reasonable certainty that the

genetic modification has not led to any changes with potentially adverse

health consequences. In general, metabolic profiling has not yet been used

commercially. However, scientists working with this technique believe

that it may play a potentially important role as a safety screening tool for

companies developing complex, compositionally altered GM foods in the

future. In addition, scientists state that it shows promise in the health care

field in assessing the safety of future new drugs.

Despite progress in developing and applying gene chips, proteomics, and

metabolic profiling, technical limitations currently prevent their use to

assess the safety of GM foods. Biotechnology experts told us that internal

standards must be developed for the methods and chemicals used in these

new technologies and that the reliability of these technologies must be

proven. For example, in gene chip testing, experts state that

standardization of the thousands of genes represented on the chips is

essential to improve the quality of this technology. Further, experts state

that the chemical analysis used in proteomics needs to be enhanced to

improve its reliability.

Beyond these technical challenges, however, lies a more fundamental

problem. Because these new technologies are more sensitive, they may

identify a flood of differences between conventional and GM food

products that existing tests could not detect. Not all of these differences

will stem from genetic modification. Some of the differences will stem

Metabolic Profiling

Challenges to Adopting

New Testing Technologies
Page 29 GAO-02-566 Genetically Modified Foods

from the tremendous natural variations in all plants caused by factors such

as the maturity of the plants and a wide range of environmental

conditions, such as temperature, moisture, amount of daylight, and unique

soil conditions that vary by region of the country. For example, there can

be a tenfold difference in the level of key compositional elements, such as

nutrients, depending on the region in which soybeans are grown. Thus,

according to a biotechnology company expert, it will be difficult to

differentiate naturally occurring changes from the effects of deliberate

genetic modifications.

Industry and university scientists have expressed strong concerns about

the problem of interpreting the potential significance of these differences.

They believe that the new technologies will be of limited value unless

baseline data on the natural variations of nutrients and other

compositional values for each of the major food crops can be developed.

However, experts disagree on the difficulty of developing this baseline.

Some experts, including those at FDA, assert that developing the baseline

will be difficult because of the extreme sensitivity of plants to

environmental variations. Other experts, especially those pioneering the

new techniques, state that a baseline can definitely be established in the

next few years.

Some companies have started to respond to the need for baseline

information. New developments in technology have begun to provide an

encyclopedic database on natural variations in plants and on the variations

resulting from deliberate genetic modification. For example, using

metabolic profiling, one company has analyzed approximately 150

characteristics, such as the size and rate of growth, of individual plants.

The company has also examined about 12,000 genes in one species of

plant—a member of the mustard family—and analyzed the consequences

of eliminating or stimulating particular genes. About one million mustard

plants of this type have been analyzed in this line of research. Even with

the development of baseline data and the detection of differences,

scientists will still need to evaluate the significance of these differences

for human health. Appendix II provides more information regarding

advancements in the development of baseline information and the

experimental use of metabolic profiling to assess the safety of GM foods.
Page 30 GAO-02-566 Genetically Modified Foods

Scientists and federal regulatory officials we contacted generally agreed

that long-term monitoring of the human health risks of GM foods through

epidemiological studies29 is not necessary because there is no scientific

evidence suggesting any long-term harm from these foods. These scientists

and officials also stated that it would be very difficult, if not impossible, to

develop a process for monitoring the long-term health risks of GM foods

because of the technical challenges in developing such a system. A recent

report by the United Nations also expresses skepticism about the

feasibility of identifying long-term health effects from GM foods.

The scientists and federal regulatory officials generally agreed that

because there is no scientific evidence that GM foods cause long-term

harm, such as increased cancer rates, there is no plausible hypothesis of

harm. Researchers need such a hypothesis in order to know what problem

to search for, test, and potentially measure. For example, in the

Framingham Heart Study of Massachusetts, researchers hypothesized that

there were biological and environmental factors that contributed to

cardiovascular disease. Using this hypothesis, researchers were able to

design a study that established a relationship between the levels of

cholesterol and the risk of heart disease. The resulting effort, comprising

more than 10,000 participants over two generations (more than 50 years),

developed groundbreaking information on the major risk factors

associated with heart disease, stroke, and other diseases. For example,

researchers found that a lifestyle typified by a faulty diet, sedentary living,

or unrestrained weight gain exacerbated disease risk factors and

influenced the occurrence of cardiovascular problems.

Without a plausible hypothesis such as that used in the Framingham study,

most scientists we contacted said that epidemiological studies on GM

foods would not provide any useful information. Two of these scientists

also noted that the primary ways in which foods might cause long-term

harm are through (1) proteins that remain stable during human digestion,

thereby retaining the potential to exert adverse effects such as a toxic

reaction, and (2) detrimental changes in nutrients and other food

components. However, for all 50 GM food plants reviewed by FDA as of

April 2002, the genetically modified proteins in those foods that potentially

 29 Epidemiological studies assess various factors influencing the occurrence, distribution,

prevention, and control of disease, injury, and other health-related events in a defined

human population. These studies often run for 20 years or more, involve thousands of

people, and cost millions of dollars.

Experts Maintain That

Long-Term Monitoring

of GM Foods Is

Neither Necessary nor

Feasible

There Is No Plausible

Hypothesis Suggesting

Long-Term Harm from GM

Foods
Page 31 GAO-02-566 Genetically Modified Foods

could be cause for concern have been shown in tests to be rapidly

digested. Further, the two GM food plants reviewed that produced

modified oils—soybean and canola—had nutritional profiles that were

similar to or better than their conventional counterparts. As discussed

previously, the soybean oil was modified to be more nutritious than

conventional soybean oil. The canola oil was modified to contain a higher

level of laurate, which would allow it to substitute for imported tropical

oils, such as palm kernel oil. However, industry determined that the total

intake of laurate in the diet would not change significantly by substituting

the improved canola oil for the tropical oil. Accordingly, industry officials

stated, and FDA officials concurred, that long-term studies of health

effects of this oil would not be needed.

Scientists and federal regulatory officials also stated that there are

substantial technical challenges that make long-term monitoring of the

health effects of GM foods virtually impossible. The challenges cited

include the following:

• Conducting long-term monitoring would require both an experimental

group that has consumed GM foods and a control group. The control

group would consist of people who could confirm that they do not eat GM

foods. In countries such as the United States, where labeling is not

required for GM foods, reliably identifying such control groups would be

virtually impossible.

• Even if GM foods were labeled in the United States, it would be very

difficult to separate the health effects of GM foods from those of their

conventional counterparts, since to date there has been very little

nutritional difference between these foods. Further, over long periods of

time, there would be practical challenges in feeding both the experimental

and controls groups diets comprising large amounts of GM food, such as

soybeans or corn, and their conventional counterparts.

• Since the long-term human health effects of consuming most foods are not

well understood, there is no baseline information against which to assess

health effects caused by GM foods.

• Changes in human food consumption patterns, specifically the addition

and removal of various foods, add new variables to the diet and compound

the difficulty of conducting long-term monitoring. The fairly recent

introduction of the kiwi fruit (to which some individuals are allergic) and

the reduction of the use of cotton seed (to which some individuals have

also been allergic) as a protein source in candy or breads illustrate the

challenges in monitoring food consumption patterns when conducting a

Technical Challenges Make

Long-Term Monitoring

Infeasible
Page 32 GAO-02-566 Genetically Modified Foods

20-to-30 year epidemiological study.

A report issued in June 2000 by the United Nations’ Food and Agriculture

Organization and World Health Organization supports the scientists’ and

regulators’ views about the infeasibility of identifying long-term health

effects from GM foods.30 The report states that, in general, very little is

known about the potential long-term effects of any foods, and that

identification of such effects is further confounded by the great variability

in the way people react to foods.31 The report also states that

epidemiological studies are not likely to differentiate the health effects of

GM foods from the many undesirable effects of conventional foods, which

according to scientists include the effects of consuming cholesterol and

fats. Accordingly, the report concludes that the identification of long-term

effects specifically attributable to GM foods is highly unlikely.

Given the challenges to long-term monitoring, federal regulatory officials,

as well as some U.S. and European scientists, state that the best defense

against long-term health risks from GM foods is an effective pre-market

safety assessment process.

Biotechnology experts believe that the current regimen of tests has been

adequate for ensuring that GM foods marketed to consumers are as safe as

conventional foods. However, some of these experts also believe that the

agency’s evaluation process could be enhanced. Specifically, FDA could

verify companies’ summary test data on GM foods, thus further ensuring

the accuracy and completeness of this data. In addition, the agency could

more clearly explain to the public the scientific rationale for its evaluation

of these foods’ safety, thereby increasing the transparency of, and public

confidence in, FDA’s evaluation process. By addressing these issues,

FDA’s assurance to consumers that GM foods are safe could be

strengthened.

To enhance FDA’s safety evaluations of GM foods, we recommend that the

Deputy Commissioner of Food and Drugs direct the agency’s Center for

Food Safety and Applied Nutrition to

 30 FAO/WHO (2000b) Safety Aspects of Genetically Modified Foods of Plant Origin. Report

of a Joint FAO/WHO Expert Consultation on Foods Derived from Biotechnology (Geneva,

Switzerland, May 29 –June 2, 2000).

31 According to scientists we contacted, this especially includes foods containing allergens.

Conclusions

Recommendations for

Executive Action
Page 33 GAO-02-566 Genetically Modified Foods

• obtain, on a random basis, raw test data from companies, during or after

consultations, as a means of verifying the completeness and accuracy of

the summary test data submitted by companies; and

• expand its memos to file recording its decisions about GM foods to

provide greater detail about its evaluations of the foods, including the level

of evaluation provided, the similarity of the foods to foods previously

evaluated, and the adequacy of the tests performed by the submitting

companies.

We provided FDA with a draft of this report for review and comment. In its

written comments, FDA stated it believes that its current process for

evaluating bioengineered foods provides appropriate oversight but agreed

that enhancements can be made. Specifically, concerning the need to

randomly review raw safety data, FDA agreed that occasional audits

would provide additional assurance to the public that pre-market

decisions about bioengineered foods are based on sound science and that

safety and regulatory issues are resolved prior to commercial distribution.

Concerning the expansion of its memos to file, the agency agreed that

providing greater detail on its decisions about the safety of GM foods

would enhance public understanding and confidence in the evaluation

process. The agency noted that actions in its proposed rule—titled

Premarket Notice Concerning Bioengineered Foods (66 FR 4706, January

18, 2001)—are relevant to our recommendations. FDA explicitly states it

will evaluate whether to adopt occasional audits as it evaluates comments

on its proposed rule. Since FDA officials told us that some of its proposed

rule changes in the Federal Register have taken years to implement, we

believe that the public’s interests would be served by implementing our

recommendations separately from the proposed rule approval process.

FDA also had general comments about the terms and definitions used in

discussing agricultural biotechnology. FDA stated that our draft report

avoided many of the pitfalls in terminology and in general was written in a

manner that will be understandable to the public. However, the agency

believes the use of terms such as “Genetically Modified Food” in the title

and “GM food” in the text can be misleading and such foods are more

commonly referred to as bioengineered foods. While perhaps the scientific

community refers to these foods as bioengineered, the lay public is more

familiar with the term genetically modified foods. Accordingly, we have

continued to use the term genetically modified, which is defined on page

one of our report.

Agency Comments
Page 34 GAO-02-566 Genetically Modified Foods

Separately from its written comments, FDA provided us with some

technical changes, which we incorporated into the report where

appropriate. FDA’s written comments are presented in appendix III.

We performed our review from July 2001 through May 2002 in accordance

with generally accepted government auditing standards. (See app. I for our

objectives, scope, and methodology.)

We are sending copies of this report to congressional committees with

jurisdiction over food safety programs, the Deputy Commissioner of Food

and Drugs, the Director, Office of Management and Budget, and other

interested parties. We will also make copies available to others upon

request. In addition, the report will be available at no charge on the GAO

Web site at http://www.gao.gov.

If you or your staff have any questions about this report, please call me at

(202) 512-3841. Key contributors to this report are listed in appendix IV.

Lawrence J. Dyckman

Director, Natural Resources and Environment
Appendix I: Objectives, Scope, and

Methodology

Page 35 GAO-02-566 Genetically Modified Foods

Representatives John Baldacci and John Tierney asked us to (1) identify

the types of potential human health risks associated with genetically

modified (GM) foods and experts’ views on the adequacy of tests used to

evaluate these risks, (2) describe the Food and Drug Administration’s

(FDA) controls for ensuring that companies submit test data it requests

and identify experts’ views on the agency’s overall evaluations of these

foods, (3) describe potential changes in future GM foods and any

associated changes needed in tests to evaluate them, and (4) identify

experts’ views on the necessity and feasibility of monitoring the long-term

health risks of these foods.

In addressing our review objectives, we interviewed representatives from

U.S. consumer groups, academic and research institutions, federal

regulatory agencies, and the biotechnology industry. We also E-mailed a

set of questions to experts representing a variety of positions on

biotechnology issues. We selected these experts in consultation with

officials from the National Academy of Science’s National Research

Council. These experts included scientists from the Center for Science in

the Public Interest, the Union of Concerned Scientists, the Biotechnology

Center of the University of Illinois, the Health Sciences Center of Tulane

University, FDA, the Aventis Corp., the DuPont Corp., the Monsanto Corp.,

and Paradigm Genetics, Inc. In addition, we analyzed reports, policy

documents, or issue papers from the Center for Science in the Public

Interest, the Consumer Federation of America, the Union of Concerned

Scientists, the Council for Agricultural Science and Technology, the

National Academy of Sciences, the Pew Initiative on Biotechnology, the

Environmental Protection Agency, FDA, the Biotechnology Industry

Organization, the Institute of Food Technologists, the Codex

Alimentarius,1

 and the National Institute for Quality Control of Agricultural

Products at the Wageningen University and Research Center of the

Netherlands. We did not assess the potential environmental risks

associated with GM food production. In addition, since there have been no

GM animals evaluated for commercialization, we did not assess the

potential environmental or human health risks associated with them.

To identify the types of potential health risks of GM foods, we analyzed

and synthesized information from the interviews, E-mail question

responses, and documents regarding these risks. To identify tests

 1

 Codex Alimentarius is the joint food standards program for the United Nations’ Food and

Agriculture Organization and the World Health Organization that was established in 1962.

Appendix I: Objectives, Scope, and

Methodology
Appendix I: Objectives, Scope, and

Methodology

Page 36 GAO-02-566 Genetically Modified Foods

commonly used by industry to assess GM food safety, we examined

several FDA evaluations of GM food. In examining these evaluations, we

also analyzed how FDA addresses any potential limitations in these tests

and what guidance FDA provides to industry regarding scientifically

acceptable tests. In our E-mail questions, we also asked the experts to

describe any limitations to these tests, and then analyzed and synthesized

their responses, particularly regarding test-specific limitations and

suggestions for improving the tests. In addition, we asked whether there

were any limitations to FDA’s guidance on acceptable tests. We then

synthesized their responses, including suggestions for improving FDA’s

guidance.

To describe FDA internal controls for ensuring that companies submit

safety test data requested by the agency, we interviewed FDA officials and

reviewed agency documents about the functions of these internal controls,

specifically (1) FDA’s 1992 Policy on Foods Derived from New Plant

Varieties and its 1997 Guidance on Consultation Procedures that

describe what safety data companies should submit; (2) the qualifications

and roles of the FDA Biotechnology Evaluation Teams responsible for

evaluating these submissions; and (3) FDA’s practice of matching its level

of evaluation to the degree of novelty of the GM food submitted. Further,

we compared the safety data specified in FDA’s 1992 policy with data

provided by companies in five GM food submissions and analyzed the

extent of the companies’ adherence to FDA’s recommended procedures

for safety assessments.2

 We contacted officials at the Department of

Health and Human Services’ Office of Inspector General to determine if

they had reviewed FDA’s internal controls. (They had not.) We did not,

however, independently verify the adequacy of FDA’s internal controls. To

identify experts’ views on the agency’s overall evaluations of GM foods, we

interviewed consumer groups, industry officials, and other experts,

analyzed their views and concerns—including any suggestions for

improving FDA’s evaluation process—and reviewed related literature. For

each concern identified with the process, we obtained FDA’s response and

then determined the extent to which FDA’s response effectively addressed

the concern or suggested a need for additional action by FDA. Further, we

examined Office of Management and Budget and GAO guidance and

policies relevant to these concerns.

 2

 The five submissions reviewed are representative of the three main types of GM plants

evaluated as of April 2002: pest-resistant plants, herbicide-tolerant plants, and plants having

modified oils.
Appendix I: Objectives, Scope, and

Methodology

Page 37 GAO-02-566 Genetically Modified Foods

To describe the potential changes in future GM foods and associated

changes needed in the tests to evaluate them, we interviewed scientists

and regulators on the likely changes in GM foods and new testing

approaches under development. We also focused several of our E-mail

questions on this topic and analyzed the responses. In addition to E-mail

respondents, we contacted experts from biotechnology companies

concerning research on new, more complex GM foods as well as new

testing approaches that may supplement or replace existing tests. We

synthesized these respondents’ and experts’ views on likely changes to GM

food and the value and challenges of using these new testing approaches.

Further, we reviewed the relevant scientific literature for discussions of

anticipated changes in GM foods and information on specific tests under

development. We also met with scientists developing one of these new

testing approaches to understand its potential value for assessing GM food

safety.

To identify the views of experts on the necessity and feasibility of

monitoring the long-term health risks of GM foods, we asked respondents

to our E-mail questions for an assessment of whether such an effort is

necessary or feasible and then analyzed their responses. Further, we

reviewed a variety of documents concerning the necessity and feasibility

of long-term monitoring, including a recent joint United Nations’ Food and

Agriculture Organization and World Health Organization report, as well as

a recent report by the National Institute for Quality Control of Agricultural

Products at the Wageningen University and Research Center of the

Netherlands. We also discussed the topic with other regulatory officials

connected with monitoring food safety. In particular, we discussed

whether the long-term effects of GM foods could be separated from other

factors that may influence human health.

Finally, we submitted a draft of this report for technical review by

scientists from industry, academia, and a consumer group, and we

incorporated their comments as appropriate.

We conducted our review from July 2001 through May 2002 in accordance

with generally accepted government auditing standards.
Appendix II: Potential Use of Metabolic

Profiling to Compare a GM Plant to Its

Conventional Counterpart

Page 38 GAO-02-566 Genetically Modified Foods

Metabolic profiling could be used as a safety-screening tool for GM foods.

Specifically, as shown in figure 3, special software has allowed one

company to graph the metabolic profile of one variety of mustard plants

and analyze the effects of genetic modifications. In the figure, the vertical

axis in each graph provides a list of different small molecules, or

metabolites, in mustard plants from this variety. The horizontal axis

measures variation or deviation from the metabolite levels in this

conventional variety. The vertical line in the middle of each graph

represents the average value for a range of small molecules, or

metabolites, in this conventional variety. In this example, the company

analyzed thousands of conventional plants from this variety to come up

with a range of naturally occurring metabolite levels. The company then

used the averages of these ranges to generate the vertical line in the

middle of the graphs. The points plotted with squares represent the levels

of small molecules in GM mustard plants. Points appearing to the right of

the center vertical line indicate increased levels of specific small

molecules, while points appearing to the left indicate decreased levels.

The graphs in figure 3 illustrate three scenarios: graph (a) shows a GM

mustard plant with small molecule levels nearly identical to its

conventional counterpart; graph (b) shows a GM mustard plant with a few

easily measurable decreases; and graph (c) represents a GM mustard plant

with many significant differences from the small molecule levels of its

conventional counterpart.

Appendix II: Potential Use of Metabolic

Profiling to Compare a GM Plant to Its

Conventional Counterpart
Appendix II: Potential Use of Metabolic

Profiling to Compare a GM Plant to Its

Conventional Counterpart

Page 39 GAO-02-566 Genetically Modified Foods

Figure 3: Metabolic Profiling of Three GM Mustard Plant Varieties in Comparison

with Baseline Data from Their Conventional Counterparts

Note:

Standard deviation is a measure of the probability that an observed value will be different from the

average value.

Graph (a)
Appendix II: Potential Use of Metabolic

Profiling to Compare a GM Plant to Its

Conventional Counterpart

Page 40 GAO-02-566 Genetically Modified Foods

Graph (b)
Appendix II: Potential Use of Metabolic

Profiling to Compare a GM Plant to Its

Conventional Counterpart

Page 41 GAO-02-566 Genetically Modified Foods

Source: Paradigm Genetics, Inc.

If baseline data on normal ranges of variation, such as those developed for

the mustard plants, can be made available for all GM food crops,

companies might use this type of testing to develop safety data. For

example, in graph (a), the absence of significant changes in the small

molecules would strongly indicate that no significant changes had resulted

from the genetic modification. Hence, a change in the risk of allergenicity,

toxicity, or antinutrients would be very unlikely. In the case represented

by graph (b), the software could determine which small molecules have

changed. Then, traditional testing techniques such as toxicity testing,

could be used to determine if the altered small molecules would have any

Graph (c)
Appendix II: Potential Use of Metabolic

Profiling to Compare a GM Plant to Its

Conventional Counterpart

Page 42 GAO-02-566 Genetically Modified Foods

effect on human health, plant growth, or crop yield. In the case shown in

graph (c), scientists would probably not proceed with development and

commercialization of the GM food in the absence of extensive evaluations

for allergens, toxins, or antinutrients, due to the significant differences in

small molecules between it and its conventional counterpart.
Appendix III: Comments from the Department

of Health and Human Services

Page 43 GAO-02-566 Genetically Modified Foods

Appendix III: Comments from the

Department of Health and Human Services
Appendix III: Comments from the Department

of Health and Human Services

Page 44 GAO-02-566 Genetically Modified Foods
Appendix III: Comments from the Department

of Health and Human Services

Page 45 GAO-02-566 Genetically Modified Foods
Appendix IV: GAO Contacts and Staff

Acknowledgments

Page 46 GAO-02-566 Genetically Modified Foods

Lawrence J. Dyckman, (202) 512-5138

James R. Jones, Jr., (202) 512-9839

In addition to the individuals above, Nathan J. Anderson, Dennis S. Carroll,

Kurt W. Kershow, and Cynthia C. Norris made key contributions to this

report.

Appendix IV: GAO Contacts and Staff

Acknowledgments

GAO Contacts

Staff

Acknowledgments
Related GAO Products

Page 47 GAO-02-566 Genetically Modified Foods

International Trade: Concerns Over Biotechnology Challenge U.S.

Agricultural Exports GAO-01-727. Washington, D. C.: June 15, 2001.

Biotechnology: Information on Prices of Genetically Modified Seeds in

the United States and Argentina GAO/T-RCED/NSIAD-00-228.

Washington, D. C.: June 29, 2000.

Biotechnology: Information on Prices of Genetically Modified Seeds in

the United States and Argentina GAO/RCED/NSIAD-00-55. Washington,

D. C.: January 21, 2000.

Related GAO Products

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