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 scienceassessing 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 shortshort- and long-term human longconsequences 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



Transposable Elements



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


NonNon-GE Techniques of Genetic Modification 

Mutation Breeding: 

Radiation Mutagenesis Chemical Mutagenesis 

Induced mutagenesis causes random changes in the DNA sequence.


Other Non-GE Techniques of NonGenetic Modification
Simple Selection  Crossing  

Interspecies Crossing

The progeny of cross-breeding cannot crossalways be predicted.

Targeted, Non-Targeted, 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? 

NonNon-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 AntiAnti-nutrients 

The level of dietary exposure 

Exposure to high-level consumers highFood habits related to culture Effect of food preparation/processing

Agronomic Comparison
Agronominc traits are evaluated in the laboratory, greenhouse, and field


Varieties with unusual features are discarded

Not sufficient for identifying all unintended changes

Feeding Trials
Test Animals are Fed Modified Whole Foods or Food Extracts


Compares nutritional quality of GE crop with its conventional counterpart  

Nutrient requirements of animal models Volume of food that can be administered Limited test dosage and exposure time

Food is a Complex Mixture
The use of targeted and non-targeted non(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 PerformancePerformance-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: 

PrePre-market to post-market feedback loop postDietary survey tools 

PerformancePerformance-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 naturallynaturallyoccurring compounds must be improved and expanded 

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