Approaches to Assessing

Unintended Health Effects of

Genetically Engineered Foods
Understanding the Science
Behind the Approach

Ann L. Yaktine, Ph.D.

Institute of Medicine
The National Academies
The USDA, FDA, and EPA asked the National
Academies to convene a committee of experts
to:

 Outline science-based approaches for

assessing or predicting unintended health
effects of genetically engineered foods, and

 Compare the potential for unintended effects

of GE foods with those derived from
conventional and other methods of genetic
modification.
Safety of Genetically Engineered
Foods: Approaches to Assessing
Unintended Effects
 The Task to the Study Panel
 Focus on mechanisms by which
unintended changes in composition of
food occur as a result of various breeding
and propagation methods
 Assess the extent to which these
mechanisms are likely to lead to significant
compositional changes in food
 Assess methods to detect unintended
changes in food in order to determine
potential human health effects
 Identify appropriate scientific questions
and methods for determining unintended
changes in food from GE organisms
 Outline methods to assess the potential
short- and long-term human
consequences of such changes
 The study focused on scientific
approaches and methodology used
to predict and assess unintended
effects.
Defining the Science
What is Genetic Engineering?
One type of genetic modification that
involves an intended targeted change
in a gene sequence to achieve a
specific result through the use of
recombinant DNA (rDNA) technology.
 rDNA Techniques
 Microbial Vectors
Electroporation
Microinjection
 Transposable Elements

ATGCCAAGCA

TCAA
TCAA ATGCCAAGCA TCGATAGCGCAAAACTAA
Genetic engineering is targeted, that is, the
gene sequence is specific and the insertion
site is known.

CATATTCTC

ATGCCAAGCA TCGATAGCGCAAAACTAA
Non-GE Techniques of Genetic
Modification

 Mutation Breeding:

 Radiation Mutagenesis

 Chemical Mutagenesis
Induced mutagenesis causes random
changes in the DNA sequence.

ATGCCAA GCA CATATTCTC TCGA AGCGCAAAACTAA

Other Non-GE Techniques of
Genetic Modification

 Simple Selection
 Crossing

 Interspecies Crossing
The progeny of cross-breeding cannot
always be predicted.
 Targeted, Non-Targeted, and
Conventional Methods of Genetic
Modification All Have the Potential
to Produce Unintended Effects.
 Genetic Engineering (Targeted Genetic
Modification)

 Impact of expressing proteins from an

unrelated species?
 Brazil nut gene into soybean

 Effects of new proteins operating through

unexpected pathways?
 Non-targeted Genetic Modification
 Cannot predict outcome due to random
changes to the gene sequence

 Conventional Crossing
 Expression pattern of new traits cannot
always be predicted
 Lenape potato
Why is predicting an unintended effect
difficult?
 Mechanisms of genetic engineering
overlap with those of other types of
genetic modification.

 Techniques used to alter the genetic

composition of an organism are
mechanistically different.
It is unlikely that all methods
of either genetic engineering
or conventional breeding will
have equal probability for
unintended effects.
It is more likely that the product
of the modification rather than
the process itself will produce an
unintended effect.
What Scientific Approaches Can Be
Used to Identify Compositional
Changes in Food that May Lead to
an Unintended Effect?
 Targeted Quantitative Analysis

 Profiling (Untargeted) Analysis

 Targeted Analysis
 Predefined
Compounds
 Amino acids
 Lipids
 Vitamins
 Other nutrients,
toxicants, allergens
 Isolated for Analysis
 Quantified
 Profiling Analysis
 Multiple Compounds
in a Sample
 Compounds
Identified and
Quantified:
 Electrophoretic
separation
 Spectrometry
 Genomic, proteomic,
etc.
 Profiling:
Genomics and Proteomics
 Genomic technology can measure the
level of thousands of transcripts
simultaneously
 Proteomic analysis detects and quantifies

individual or groups of proteins

 Toxicity Testing

 Agronomic Comparisons

 Feeding Trials
Application, Validation, and
Limitations of Tools for
Identifying and Predicting
Unintended Effects
 Any adverse health effect from
unintended compositional changes
will be a consequence of:
 The inherent toxicity of the compound
 Allergens
 Toxins/toxicants
 Anti-nutrients

 The level of dietary exposure

 Exposure to high-level consumers
 Food habits related to culture
 Effect of food preparation/processing
 Agronomic Comparison
Agronominc traits are evaluated in the
laboratory, greenhouse, and field

APPLICATION LIMITATION

 Varieties with unusual  Not sufficient for

features are discarded identifying all
unintended changes
 Feeding Trials
Test Animals are Fed Modified Whole Foods
or Food Extracts

APPLICATION LIMITATIONS

 Compares nutritional  Nutrient requirements

quality of GE crop of animal models
with its conventional  Volume of food that
counterpart can be administered
 Limited test dosage
and exposure time
Food is a Complex Mixture

The use of targeted and non-targeted

(profiling) methods to assess the
safety of genetically modified foods is
increasing, however, there are
limitations to our ability to interpret
and utilize the information generated.
The complexity of food composition
challenges the ability of modern
analytical chemistry and bioinformatics
to identify compositional changes and
determine their biological relevance.
Looking to the Future
Although the array of analytical and
epidemiological techniques has increased,
gaps remain in our ability to:

 Identify compositional changes that result

from genetic modification
 Determine the biological relevance of such
changes to human health
 Devise appropriate scientific methods to
predict and assess unintended effects
 Recommendations from the Study
Develop and employ:

 Standardized Sampling Methodologies

 Validation Procedures

 Performance-based Techniques for Targeted

Analysis and Profiling

 Integrated Database of Food Composition from

Industrial and Regulatory Agency Sources
 Standardized Sampling
Methodologies
Should include:

 Comparison of modified foods to unmodified

varieties developed under a variety of
environmental conditions

 Comparison of modified foods to commonly

consumed commercial varieties
 Validation Procedures
The tracking potential of all
genetically modified foods should be improved ,
including:

 Pre-market to post-market feedback loop

 Dietary survey tools

 Performance-Based Techniques for
Targeted Analysis and Profiling
 Scientific methods to detect unintended
compositional changes must be continually
scrutinized for accuracy, validity, and application

 Current databases of novel and naturally-

occurring compounds must be improved and
expanded
 Acknowledgements

The Institute of Medicine and the Division of

Earth and Life Sciences, The National
Academies
The Committee to Identify and Assess
Unintended Effects of GE Foods on Human
Health, Dr. Bettie Sue Masters, Chair