2-Plants: Some scientific thoughts on the principle of substantial equivalence
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TITLE: The Promise of Plant Biotechnology -
The Threat of Genetically Modified Organisms
SOURCE: Patrick Brown, University of California
DATE: July 2000
-------------------- archive: http://www.gene.ch/ --------------------
The Promise of Plant Biotechnology - The Threat of Genetically
College of Agriculture & Environmental Science
University of California
Davis, CA 95616
Crop cultivars developed using recombinant-DNA technologies (rDNA
crops) have been rapidly adopted by agricultural producers in the
United States; and until recently, foods derived from these crops
have been tacitly accepted by US consumers. In contrast, many
European consumers have shown a marked resistance to these
technologies, which, in turn, has resulted in the passage of trade
restrictions and of laws that limit the import, growth or use of rDNA
crops throughout much of Europe. The public uproar in Europe, and the
protests surrounding the World Trade Organization meeting in Seattle,
has now raised the awareness of many in the USA and given birth to a
vocal and growing group of concerned consumers.
The intensity of the current debate has surprised many in the
scientific community and has escalated into a highly polarized and
increasingly antagonistic debate. Scientists, and the professional
organizations that represent them, have been publicly supportive of
this technology and often dismissive of public concerns. Most
scientific comment suggests that 'education' is the key to gaining
the needed acceptance, while almost no comment has recognized or
addressed the fears of the public. Those who oppose rDNA technology
interpret the apparent willingness of the US scientific community to
embrace this new technology, while failing to adequately address the
potential risks, as a betrayal of public trust.
Public uncertainty has resulted in the loss of markets, and will
increasingly do so, for the current generation of rDNA crops and
foods. Though this is clearly of substantial economic concern, by far
the most significant consequence of public concern is the threat that
this conflict poses for the entire field of plant biotechnology,
which holds far greater promise of human benefit than that offered by
any existing rDNA crop. The loss of this technology through careless
and premature implementation would be truly devastating to the goal
of developing more abundant and nutritious foods in an
environmentally sensitive fashion.
This issue requires immediate and thoughtful attention from plant
scientists. We must recognize that our knowledge of the processes
that regulate gene incorporation and expression are in their infancy
and that our capacity to manipulate the plant genome is crude. Given
this current lack of understanding it is certainly possible that the
current regulatory safeguards are inadequate and may not be offering
sufficient protection against inadvertent creation of health and
Since the public education and research system is based upon a
foundation of public trust, it is essential that we recognize and
admit the unknowns associated with molecular biology and act with
caution and integrity.
The following text describes some of the uncertainties associated
with rDNA technology and illustrates how the scientific community's
defence of the current generation of rDNA crops represents a
substantial threat to the future of this promising new technology.
Are the Current Generation of rDNA Crops, and the Regulatory System
that approved them, Scientifically Defensible?
In 1989 the National Research Council, following extensive scientific
review, publicly concluded that crops derived from rDNA techniques do
not differ substantially from those derived using traditional
techniques. This conclusion forms the basis for current FDA policy
that regulates the production and use of rDNA crops and foods. This
conclusion is based upon the principle of "substantial equivalence"
which states that the introduction of a gene of known and safe
function into a crop of known characteristics is technologically
neutral, hence the resulting crop can be presumed to be safe and is
not subject to mandatory testing prior to release or use in foods. As
this principle is central to the scientific and regulatory acceptance
of this technology it deserves careful examination.
Is There Equivalence between rDNA and 'Traditional' Sexual Gene
To adequately compare these technologies it is essential that each is
well characterized and understood. The molecular processes that
control gene incorporation and expression following a normal sexual
crossing event, however, are only poorly understood and the extent of
our ignorance is further revealed weekly as new processes involved in
the regulation of gene expression in plants are determined. The
inadequacy of our understanding is well illustrated by the host of
genetic phenomena (such as co-suppression, intron-mediated
enhancement, transcriptional regulation, protein-gene interactions
etc) for which we have essentially no mechanistic understanding. Our
knowledge of these processes is clearly in its infancy and few would
claim that we understand more than a small percentage of the
processes regulating sexual reproduction in plants.
Further, most of what is known of gene transfer using traditional and
rDNA techniques illustrates the profound manner in which they differ.
Traditional crossing involves the movement of clusters of
functionally linked genes, primarily between homologous chromosomes,
and including the relevant promoters, regulatory sequences and
associated genes involved in the coordinated expression of the
character of interest in the plant. The molecular regulation of this
process and the biochemical and evolutionary significance of these
controls is poorly understood.
In contrast to traditional techniques, current rDNA technologies
(those used in all currently approved rDNA crops) involve the random
insertion of genes in the absence of normal promoter sequences and
associated regulatory genes. As there are very few examples of plant
traits in which we have identified the associated regulatory genes,
the introduction of a fully 'functional' gene using rDNA techniques
is currently not possible. R-DNA techniques also involve the
simultaneous insertion of viral promoters and selectable markers and
facilitates the introduction of genes from incompatible species.
These genetic transformations cannot occur using traditional
approaches - which further illustrates the profound manner in which
these processes differ.
Genetic material can be moved within and between species by the
poorly understood processes of gene transposition. Though the
occurrence of this phenomenon in traditionally bred plants is
superficially equivalent to rDNA techniques (which involve the random
insertion of "artificial transposons"), the mechanisms governing this
process and the significance of transposition in traditional gene
transfer are unknown. Given our profound lack of understanding of
these processes it is impossible to compare sensibly the two
processes. Indeed, it can be argued that gene transfer via rDNA
techniques resembles the process of viral infection far more closely
than it resembles traditional breeding.
In summary, it is clear that gene transfer using rDNA techniques is
substantially different from the processes that govern gene transfer
in traditional breeding. The extent to which these processes differ
will become increasingly clear as we gain a better understanding of
the processes governing gene movement, expression and regulation.
The presumption of "Substantial Equivalence" - the basis for current
regulatory principles - is profoundly flawed and scientifically
Do rDNA Techniques offer Greater Precision?
One of the much-touted benefits of r-DNA techniques is the capability
to introduce only a discrete and well-defined number of genes into
the new cultivar whereas a traditional crossing event introduces
thousands of genes. This ability to control the types and numbers of
genes introduced speeds the introduction of a gene of interest by
eliminating the need for extensive backcrossing to the elite parent.
Many have suggested that this approach is fundamentally more
"precise" than traditional breeding techniques and have argued that
the technique is consequently "safer".
The ability to introduce a precisely defined compliment of genes
using rDNA techniques, however, is not equivalent to the introduction
of a precisely defined and biologically integrated character. Whereas
the incorporation of a new character using traditional techniques
occurs in a fully functional and appropriately regulated manner, rDNA
gene introduction is more or less random, and does not involve
introduction of the regulatory sequences normally associated with
that gene. Traditional techniques, therefore, result in greater
"biological precision" than random gene insertion using rDNA
The FDA policy statement further suggests that it is highly unlikely
that rDNA techniques will result in the inadvertent production of
allergens or toxic compounds and that once incorporated into the
genome, the introduced gene functions like all other genes in the
genome. These statements are offered in support of the premise that
rDNA experiments are more predictable than traditional breeding
approaches. This presumption is, however, clearly contradicted by a
large volume of scientific literature and experimental experience
that illustrates the propensity of rDNA techniques to produce
unexpected and often lethal perturbations. Indeed metabolic and
phenological perturbations are very frequently observed following
transformation events and a high percentage of transformants show
profound growth aberrations. Indeed the propensity of random gene
introduction to cause metabolic disruption is well documented and
actively used to probe gene function.
While extreme aberrations can be easily selected out, it is also
highly likely that undetected biochemical perturbations remain
following essentially all transformation events. Since it is not
standard practice to screen transformants there is clearly a
potential for biochemically abnormal transgenic plants to persist.
This is further exacerbated through the use of tissue culture and
embryo rescue etc. which can be used to "rescue" metabolically
altered transgenic plants that might otherwise have been eliminated
during early plant growth. Whether or not these same perturbations
occur following traditional breeding is unknown. Lack of knowledge,
however, is not proof of safety.
The metabolic perturbations caused by rDNA gene introduction may
result in production of toxic compounds. Many plant species have the
capacity to produce toxic compounds which, under natural conditions,
serve to protect against animal and insect predation as well as
contributing to disease resistance mechanisms. In certain species,
such as those in the Solanum family, there are many well-
characterized and highly unpalatable or toxic compounds. It is very
likely that the majority of the genes involved in the formation of
these toxic and unpalatable compounds are still present (though not
expressed) in modern tomato and potato. Given the random nature of
rDNA gene insertion, and the use of a promiscuous viral promoter
sequence, the potential clearly exists that tomato could be induced
to produce a toxin as a result of an rDNA gene transfer. Whether this
would occur with the same frequency following traditional sexual
breeding is unknown. The presumption that it cannot occur is clearly
Clearly the assumption that a transformed crop is exactly the sum of
the original crop and the introduced gene is not acceptable. RDNA
techniques are profoundly different from traditional breeding methods
and are well known to cause unexpected metabolic perturbations. The
principle of substantial equivalence is not scientifically
justifiable; hence we can make no a priori assumption of the safety
of any rDNA manipulation.
Do rDNA Techniques Provide an Acceptable Level of Risk?
The preceding discussion clearly demonstrates that the risks
associated with rDNA technology cannot be determined given current
understanding of gene expression. Nevertheless it has been argued
that risk is a normal part of technological advancement and that
acceptance of this risk is warranted in the instance of rDNA crops.
While it is true that we accept risks as a normal part of life, most
of the risks we accept are defined by experience and are understood
before they are taken. Some risks are also taken because the rewards
are perceived to outweigh the risks. Traditional breeding has on the
whole been an acceptable risk with 10,000 years of experience, and a
trust in the motives of those producing the new cultivars.
Many, however, are not yet prepared to accept the risks of rDNA
technologies. This is in part due to a lack of understanding of the
risks, the minimal benefit of the current crop of GMOs, and a
mistrust of the motives of those selling the technology. Given the
current state of our knowledge of this technology and the nature of
the GMOs currently available, this lack of public trust is entirely
reasonable. Public acceptance will require convincing demonstration
of safety and the development of crops with a more direct benefit to
The concerns expressed by many are further validated by the current
generation of GMOs that have been incorporated into the food system
without adequate public consultation and scientific scrutiny. The
current generation of GMO crops do not provide any tangible public
benefit, have not contributed to reduced food costs, and have no
confirmed ecological benefit. This is well illustrated by the two
most prevalent types of GMOs in use in the US.
Insect-resistant crops containing the gene encoding the Bacillus
thuringiensis toxin have been planted widely in the US. This
transgenic technique promises to reduce the use of pesticides and
reduce growers' costs. While reduction in pesticide use is an
admirable goal there are significant grounds to question the
appropriateness of the current generation of Bt-producing crops and
to question the haste with which these crops were released for
The current generation of Bt crops utilize a single Bt gene rather
than the complex of Bt genes that are available. There is widespread
agreement amongst scientists that this use of a single Bt gene will
increase the speed with which pest resistance will develop. To help
alleviate the development of insect resistance the USDA and Monsanto
now advise growers to plant refuge areas to ensure non-resistant
insects persist under the premise that this will reduce the rate of
resistance development. While this is theoretically sound there is
insufficient ecological data to determine optimal size of these
refuges or to estimate how effective they will be.
The current generation of Bt crops also utilize antibiotic resistance
as the selectable marker and rely upon viral promoters to ensure high
degrees of expression. This clearly introduces a risk associated with
a promoter designed to be free of regulatory controls, it excites
those who see viral and antibiotic-resistance genes as threatening,
and it ensures that the Bt protein is distributed uniformly
throughout the plant. The uniform presence of the Bt protein enhances
the likelihood of resistance development and ensures that the protein
is present throughout plant development and is present in the pollen.
The death of Monarch larvae was a direct consequence of the presence
of active Bt toxin in the pollen.
While some have questioned the scientific relevance of this study it
did illustrate the inherent flaws in this cultivar.
Methods exist (or will soon exist) that make the use of viral
promoters and antibiotic resistance markers unnecessary. There is no
justification for the expression of Bt in the pollen, and the release
of cultivars with a single Bt gene is certain to hasten resistance
development. In the absence of data to support the refugia concept
there is very little to prevent the development of widespread insect
tolerance of Bt.
Clearly the release of the first generation of Bt-containing crops
was premature and based upon flawed scientific principles. Regulatory
and scientific support for this cultivar is clearly questionable.
The other dominant type of GMO in use today is the Roundup-Ready
varieties of cotton, soybean and corn. Not only do these cultivars
contain many of the same questionable genes as those in Bt crops, but
also they have the additional propensity to contribute to the
development of herbicide-resistant weed species for which the
consequences are poorly understood. Roundup-Ready crops are also of
questionable ecological value and build a long-term dependence on the
use of the herbicide Glyphosate.
Not insignificantly, the overtly 'corporate' nature of these crops
and the dependence they build on high cost and ecologically
questionable technologies has resulted in widespread suspicion of the
motives of those promoting these cultivars.
It is abundantly clear that the current generation of GMOs were
developed using an untested and unsophisticated technology and were
released prematurely to ensure early returns on corporate investment.
Clearly this does not represent a sound justification for the release
and widespread use of these crops.
Perhaps one of the most profoundly flawed justifications of GMOs is
illustrated in the often-cited refrain "GMO foods have been widely
available in the marketplace for the past 5 years and not one
incident of harm to public health has been documented". Since every
introduced gene is inserted into a different genetic location, and
every gene differs in functions and interactions within the genome,
and as every species can be expected to 'react' differently to the
gene introduction process, it is clear that the safety of one GMO is
in no way predictive of the safety of another. In many respects the
claim of safety by association is no more valid than the claim that
the safety of aspirin predicts the safety of all future drugs.
The real threat to the future of plant biotechnology is the
irresponsible and premature releases of the first generation of GMOs
that are full of unsound scientific assumptions, rife with careless
science, and arrogantly dismissive of valid concerns. The current
generation of GMOs provide little real benefit except corporate
profit and marginally improved grower returns, while at the same time
introducing a host of poorly studied human and ecological risks. Not
surprisingly, many have questioned the value of these crops and the
integrity of those who support their use.
Given these issues and the overall lack of knowledge of rDNA
technology it can only be concluded that the current FDA regulations
guiding the release and testing of GMOs is inadequate. It can further
be concluded that the technology is inadequately developed to ensure
its safety. In the absence of a sound scientific basis to predict the
full consequences of rDNA crop development, we must either subject
all new crops to a rigorous testing program that considers all
potential health, social and environmental concerns or halt further
release of rDNA crops until a firm scientific understanding of the
biological principles is attained.
As scientists it is our responsibility to recognize that we do not
yet have sufficient knowledge of the process to use it safely. We
must work towards addressing all of the concerns explicit in the
current generation of crops, and must support a rigorous testing
program to ensure the safety of all GMO foodstuffs in the interim. To
date many in the scientific community have been unwilling to
rationally consider the concerns surrounding the current GMOs and
have wrongly considered that a defence of GMOs is a prerequisite to
protect the science of plant biotechnology. Nothing could be further
from the truth or more threatening to the future of this technology.
To find out more about how the FDA in the US has blatantly ignored
the advice of its own scientists in assessing such risks see:
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