Brian Ellis
Biotechnology Laboratory - UBC
May 02, 2001
Health Canada is mandated
to ensure that the Canadian
public is not put at risk from
food or health care products
HC must assess all novel foods
Origins of Novel Foods
From other geographic regions
From new manufacturing processes
From plant breeding
Assessment of Novel Foods
History of safe human consumption?
Contains known toxicants?
Nutritional value altered?
Plant Breeding
Development and evaluation
of new genotypes
1. Create variation
2. Select
3. Repeat….
Classical Plant Breeding
1. creates new allelic combinations
within a species genome
2. samples mutational /
recombinational changes
Induced mutants
Distantly related species
Closely-related species
Selections
Landraces
Existing varieties
SEXUAL CROSSES
Progeny Evaluation
products of plant breeding
are generally regarded
as safe
“barley is barley is barley”
•  long history
•  highly selected
How do GMO genotypes
fit within this model?
derived from known (GRAS)
germplasm
very few new genetic elements
added to parental variety
The conundrum….
Do a comprehensive (and slow
and expensive) food safety
assessment ?
The conundrum….
…or assume that the genetic
background is benign,
assess traits directly related to
the transgene, and
establish “substantial equivalence”
Substantial Equivalence
comparison of the GMO product
with the conventional
assesses differences between them
focuses on the transgene and on
hallmarks of conventional genotype
Substantial Equivalence
Strengths
Focuses on most likely impacts
Uses established methodologies
Substantial Equivalence
Weaknesses
Assumes linear responses to
genetic change
Uses targeted rather than global
analytical methodologies
Differential gene expression in the Arabidopsis hypocotyl
ein 4 mutant
-15
-10
wildtype
-5
0
5
10
15
S. Regan, Carleton U.
PLEIOTROPY
Cellular systems are highly
integrated at all levels
Plant metabolism is extraordinarily
plastic - adapted to creation of
new metabolites
Metabolic shifts induced by single-gene changes
in Arabidopsis thaliana
dgd-1
sdd-1
Fiehn et al, Nature Biotechnology (2000)
Strengthening
Substantial Equivalence
Assume that pleiotropic effects
will occur in GMO organisms
Develop and adopt global
profiling methodologies
Focus safety assessment on
revealed differences