Brian EllisBiotechnology Laboratory - UBCMay 02, 2001

Health Canada is mandatedto ensure that the Canadianpublic is not put at risk fromfood or health care products

HC must assess all novel foods

From other geographic regions

From new manufacturing processes

Origins of Novel Foods

From plant breeding

History of safe human consumption?

Contains known toxicants?

Assessment of Novel Foods

Nutritional value altered?

Plant Breeding

Development and evaluationof new genotypes

1. Create variation

2. Select

3. Repeat….

1. creates new allelic combinations within a species genome

2. samples mutational / recombinational changes

Classical Plant Breeding

Progeny Evaluation

SEXUAL CROSSES

Existing varieties

Distantly related speciesInduced mutants

Closely-related species

LandracesSelections

products of plant breedingare 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 elementsadded to parental variety

Do a comprehensive (and slowand expensive) food safety assessment ?

The conundrum….

…or assume that the genetic background is benign,

The conundrum….

assess traits directly related to the transgene, and

establish “substantial equivalence”

comparison of the GMO productwith the conventional

Substantial Equivalence

assesses differences between them

focuses on the transgene and on hallmarks of conventional genotype

Strengths

Substantial Equivalence

Focuses on most likely impacts

Uses established methodologies

Weaknesses

Substantial Equivalence

Assumes linear responses to genetic change

Uses targeted rather than global analytical methodologies

Differential gene expression in the Arabidopsis hypocotyl

wildtypeein 4 mutant

S. Regan, Carleton U.

Cellular systems are highly integrated at all levels

PLEIOTROPY

Plant metabolism is extraordinarilyplastic - adapted to creation of new metabolites

Fiehn et al, Nature Biotechnology (2000)

Metabolic shifts induced by single-gene changes

in Arabidopsis thalianadgd-1

sdd-1

Assume that pleiotropic effectswill occur in GMO organisms

Strengthening Substantial Equivalence

Develop and adopt global profiling methodologies

Focus safety assessment on revealed differences