Principles of Plant Genetics and Breeding

272 CHAPTER 15
Concept of substantial equivalence in the
regulation of biotechnology
A major challenge facing regulatory agencies the world
over is in deciding what constitutes a meaningful difference
between a conventional crop cultivar and its genetically
modified derivative. The concept of substantial
equivalence originates from the general position taken
by regulators to the effect that conventional cultivars
and their GM derivatives are so similar that they can
be considered “substantially equivalent”. This concept,
apparently, has its origins in conventional plant breeding
in which the mixing of the genomes of plants
through hybridization may create new recombinants
that are equivalent. However, critics are quick to point
out that this is not exactly what obtains with genetic
engineering. In conventional breeding, the genes being
reshuffled between domesticated cultivars have had the
benefit of years of evolution during which undesirable
traits have been selected out of most of the major crops,
though the use of a wild relative for breeding purposes
could introduce genes potentially detrimental to human
health. In contrast, the genes involved in GM crop production
have been introduced into unfamiliar genetic
backgrounds.
The traditional method of evaluating new cultivars
from breeding programs is to compare them with the
existing cultivars they would replace, if successful. To
this end, evaluations include gross phenotype, general
performance, quality of product, and chemical analysis
(especially if the goal of the breeding program is to
improve plant chemical content). It is expected (or at
least hoped) that the new cultivar will not be identical to
the existing cultivar, because of the investment of time
and effort in breeding. Nonetheless it is not expected
that the new cultivar would produce any adverse effects
in users of the product. On the other hand, there are still
genes detrimental to human health in wild relatives used
for breeding, and, in principle, mutagenic methods used
to generate diversity in breeding programs could also
cause changes that impact food safety or quality.
In 1995, the World Health Organization (WHO)
released a report in which the concept of substantial
equivalence was endorsed and was promoted as the basis
for safety assessment decisions involving genetically
modified organisms and products. Since then, the concept
has attracted both supporters and opponents. Some
feel that, as a decision threshold, the concept is vague,
ambiguous, and lacks specificity, setting the standard of
evaluation of GM products as low as possible. On the
other hand, supporters believe that what is intended is
for regulators to have a conceptual framework, not a scientific
formulation, that does not limit what kinds and
amounts of tests regulators may impose on new foods.
The concept of substantial equivalence has since been
revisited by the Food and Agricultural Organization
(FAO) and WHO and amended. It appears that opposition
to the use of this concept as a regulatory tool would
be minimized if a product is declared substantially
equivalent after rigorous scientific analysis has been conducted
to establish the GM product poses no more
health or environmental risk than its conventional counterpart.
Of course the cost of such an evaluation may
prohibit the use of biotechnology varieties unless there
are great benefits from their use.
Issue of “novel traits”
Sometimes, conventional plant breeding may introduce
a “novel trait” into the breeding program through wide
crosses or mutagenesis. This notwithstanding, the new
cultivar produced is still considered substantially equivalent
to other cultivars of the same crop. On the other
hand, even though the presence of a transgene in a GM
cultivar is considered to be an incorporation of a “novel
trait”, the GM product and the conventional product
differ. The novel traits incorporated in the major commercially
produced GM crops are derived from nonplant
origins (mainly from microorganisms). Secondly,
only a single gene separates a GM product from its
derivative. In conventional breeding, the desired genes
are transferred along with numerous other unintended
genes.
The question then is whether the more precise gene
transfer of genetic engineering means that a GM crop
and its traditional counterpart differ only in the transgene
and its products. If this were so, a simple linear
model would be adequate to predict the phenotype of a
GM organism. Unfortunately, because of the role of the
environment in gene expression, and the complex interactions
that occur in a biological system, linear models
are seldom adequate in predicting complex biological
systems. Further, it is known that single mutations often
produce pleiotropic effects (collateral changes) in the
organism. Similarly, collateral effects of a transgene have
been demonstrated in transgenic salmon carrying the
transgene coding for human growth hormone, in which
researchers found a range of phenotypes. Also, it is
important to mention that the altered phenotypes may
appear at particular growth times in the growth cycle of
the organism, or in response to specific environmental