How Gene-Splicing is Radically Different fromConventional
Agriculture--Dr. Michael Hansen of the Consumers Union

Web Master Note: A Central Myth upheld by the proponents of Genetic
Engineering is that agricultural biotechnology or gene-splicing is just an
extension of conventional plant breeding. In the article below, a letter
sent in to the Food and Drug Administration as part of an official comment
period on GE foods and crops, Dr. Michael Hansen, one of America's
preeminent critics of genetic engineering, demolishes this myth.

genetic engineering differs from conventional breeding, hybridization, wide
crosses and horizontal gene transfer

Jan. 27, 2000
Michael K. Hansen, Ph.D.
Research Associate
Consumer Policy Institute/Consumers Union

Genetic engineering is not just an extension of conventional
breeding. In fact, it differs profoundly.

As a general rule, conventional
breeding develops new plant varieties by the process of selection, and seeks
to achieve expression of genetic material which is already present within a
species. (There are exceptions, which include species hybridization, wide
crosses and horizontal gene transfer, but they are limited, and do not
change the overall conclusion, as discussed later.) Conventional breeding
employs processes that occur in nature, such as sexual and asexual
reproduction. The product of conventional breeding emphasizes certain
characteristics. However these characteristics are not new for the species.
The characteristics have been present for millenia within the genetic
potential of the species.

Genetic engineering works primarily through insertion of
genetic material, although gene insertion must also be followed up by
selection. This insertion process does not occur in nature. A gene
"gun", a bacterial "truck" or a chemical or electrical treatment inserts the
genetic material into the host plant cell and then, with the help of genetic
elements in the construct, this genetic material inserts itself into the
chromosomes of the host plant. Engineers must also insert a "promoter" gene
from a virus as part of the package, to make the inserted gene express
itself. This process alone, involving a gene gun or a comparable
technique, and a promoter, is profoundly different from conventional
breeding, even if the primary goal is only to insert genetic material from
the same species.

But beyond that, the technique permits genetic material to
be inserted from unprecedented sources. It is now possible to insert
genetic material from species, families and even kingdoms which could not
previously be sources of genetic material for a particular species, and even
to insert custom-designed genes that do not exist in nature. As a result we
can create what can be regarded as synthetic life forms, something which
could not be done by conventional breeding.

It is interesting to compare this advance to the advances
that led to creation of synthetic organic chemicals earlier in the 1900s.
One could argue that synthetic chemicals are just an extension of basic
chemistry, and in certain senses they are. Yet when we began creating new
chemicals that had not previously existed on the earth, or which had only
been present in small quantities, and began distributing them massively, we
discovered that many of these chemicals, even though they were made of the
same elements as "natural" chemicals, had unexpected adverse properties for
the environment and health. Because we had not co-evolved with them for
millenia, many (though by no means all) had negative effects. Among the
serious problems were PCBs and vinyl chloride, which were found to be
carcinogens, and numerous organochlorine pesticides, which were found to be
carcinogens, reproductive toxins, endocrine disruptors, immune suppressors,
etc. After several decades of use, these effects caused such concern that
we passed the Toxic Substances Control Act which required premarket
screening of synthetic organic chemicals by EPA for such effects as
carcinogenicity, mutagenicity and impact on wildlife, and changed our
pesticide rules similarly. There are many ways in which these two
scientific advances are not analogous, but the experience with synthetic
organic chemicals underlines the potential for unexpected results when novel
substances are introduced into the biosphere.

We will discuss three specific ways in which genetic
engineering differs from conventional breeding, and some of the implications
for safety, in more detail. The argument is frequently made that genetic
engineering is not only an extension of conventional breeding, but is more
precise, and therefore safer. We believe that in fact it represents a
quantum leap from conventional breeding, is more precise in one way, but
more unpredictable in others. We will discuss the following key areas of
difference and their implications for unexpected effects: scope of genetic
material transferred/unnatural recombination, location of the genetic
insertions, and use of vectors designed to move and express genes across
species barriers. As a subset of the last category there is the use of
foreign promoters (genetic "on" switches) and foreign marker genes
(particularly genes coding for antibiotic resistance). Finally we will
discuss implications for FDA policy.

Scope of Gene Transfers

As for the scope of genetic material transferred, genetic
engineering allows the movement of genetic material from any organism to any
other organism. It also offers the ability to create genetic material, and
expression products of that material, that have never existed before.

This radically differs from traditional breeding, which
merely permits the movement of genetic material between different varieties
within species, between closely related species, or closely related genera.
Even hybridization and wide crosses cannot move genetic material much beyond
these limits. The vast bulk of hybrid crops consist of the mating of two
genetically pure lines (i.e. lines that are homozygous for all alleles) of
the same crop to create a line which is heterozygous. Thus, hybrid corn is
simply the crossing of two pure corn varieties to produce a mixed line.
Occasionally, though, in conventional breeding, plant breeders will cross a
wild relative of a crop (usually a different species within the same genus)
in order to transfer particular traits from that wild relative (such as
resistance to a given disease) to the crop. However, hybrids between two
species are also known to occur naturally, although such hybrids are
primarily restricted to plants with certain characteristicsosuch as
perennial growth habitowhich most crop plants lack (Ellstrand et al., 1996).

Wide crosses, also used by breeders, also occur in nature,
but they are rare. When breeders perform wide crosses, they mate two
different genera. While the pollen of species A may successfully fertilize
the egg of species B, the embryo may not be able to naturally survive and
develop into a seedling. The plant breeder, through a technique called
embryo rescue, will remove such an embryo from the original hybrid seed and
put it into a nutritional environment in the laboratory (one containing
various nutrients and plant hormones) and raise it into seedling and adult
plant. While such wide crosses are artificial in one sense (the plant
wouldn't normally germinate or survive to adulthood), they still represent
the mixing of genomes from plants that are fairly closely related and in
which fertilization can occur. Wide crosses will happen between plants from
two different genera within the same family and often the same sub-family.
Wide crosses cannot be achieved with plants from widely different families.
Thus, while wide crosses, as breeders perform them, do not occur in nature,
they represent only a slight stretching of the boundaries of what can occur
in nature. In a sense wide crosses represent a stretching of these
boundaries by inches compared to miles with GE. After all, with GE, one can
mix genes not only from widely different plant families, one can put genes
from any organism on earth, or can create genes which have not existed
before and put them, into plants.

The mixing of genes from very different sources is likely
to introduce new elements of unpredictability. Because conventional
breeding, including hybridization and wide crosses, permits the movement of
only an extremely tiny fraction of all the genetic material that is
available in nature, and only allows mixing, and recombination, of genetic
material between species that share a recent evolutionary history of
interacting together, one would expect that the products of conventional
breeding would be more stable and predictable. The genome is a complex
whole made up in part of genes and genetic elements that interact in complex
regulatory pathways to create and maintain the organism. Any new genetic
material that enters the genome must fit into this complex regulatory whole
or it may end up destabilizing the whole. Think of the genome as a complex
computer program or as an ecological community. When one introduces a new
subprogram within the larger complex computer program, no computer
programmer can reliably predict what will happen. Because of the complexity
of such large programs, a small new subprogram can have unpredictable
effects and may ultimately cause the whole program to crash. With a complex
ecosystem, the introduction of a new species can have a range of effects,
from virtually nothing to a catastrophic effect on the ecosystem; most of
these changes cannot be reliably predicted knowing just the biology of the
introduced species.

The view that genetic engineering may be more prone to
unexpected outcomes because it creates profound disruption in the normal
interactions of genes is supported by differences in the success rate in
producing viable stable offspring, for genetic engineering versus
conventional breeding. In nature, most offspring are viable; the vast
majority of seeds germinate and produce organisms that survive and
reproduce. In conventional breeding, scientists grow many plants and keep
only a few with the most desirable traits; however the ones they discard are
still almost always normal examples of the species. This is not true for
products of genetic engineering. In the early days of GE, although one
could select cells which contained and expressed the desired trait (due to
the use of marker genes), it was necessary to attempt to grow the engineered
cells into whole plants to determine the overall impacts of the GE. A very
large percentage of the transformed cells either were not viable, were
grossly deformed, or failed to stably incorporate the desired trait, i.e.
failed to produce that trait in the plant in successive generations (Crouch,
personal communication). Some of the malformations may be due to
difficulties with tissue culture of the transformed cells; however
unexpected genetic effects also appear to be a causative factor. In fact,
only one in thousands (or tens of thousands or in some cases even millions)
of attempts achieves the desired results in terms of a seed that
incorporates the desired traits, and expresses them in a useful fashion
generation after generation, and doesn't have undesirable side effects.
Assertions that genetic engineering is a highly precise process therefore
seem misleading.

Location of Gene Insertion

GE can control relatively precisely the trait that is being
inserted into a host plant genome. However it cannot yet control the
location where the trait is inserted into the genome with any precision, nor
guarantee stable expression of the transgene. The process of insertion of
foreign genetic material via GE into the host plant genome and the
expression of such material is called transformation. Transformation is
currently accomplished through several relatively crude methods which are
relatively random in where the genes end up. One transformation method
frequently used consists of a manipulating a bacteria in the genus
Agrobacterium. These bacteria are among the few known which can transfer
their genetic material to another kingdom/phyla. These bacteria cause a
disease in plants (either a tumor-like growth called crown gall disease at
the infection site, or uncontrolled sprouting of roots from the infection
site) by attaching to the plants, transferring bacterial DNA into the plant
and getting that DNA incorporated into the host plant genome.
Agrobacterium-mediated plant transformation involves engineering the
Agrobacterium by deleting the disease-inducing genes, retaining the
bacterial transfer DNA (T-DNA) and inserting the genetic traits/elements to
be transferred. This engineered Agrobacterium, sometimes called a bacterial
"truck" is then just mixed with the desired plant cells and allowed to
transform/infect them. The use of Agrobacterium-mediated transformation
occurs primarily with dicots (non-grass like plants) and is difficult to do
with grains.

The direct gene introduction methods include chemical
treatment or electroporation of protoplasts and use of the "gene gun."
Chemical treatment or electroporation consists of exposing plants to
chemicals or an electrical field that makes the protoplasts' cell membrane
more "porous" facilitating the uptake of DNA from the surrounding medium.
The gene gun is used to "shoot" microscopic particles (such as gold) covered
with DNA into the plant tissues themselves. In all three cases, once the
DNA is in the plant cell it still needs to be incorporated in the host
genome. This is done using genetic elements (T-DNA) from Agrobacterium.
The direct gene introduction methods are often used in transforming cereals
which are fairly resistant to Agrobacterium-mediated transformation.
Furthermore, the direct introduction methods routinely lead to insertion of
multiple copies of the genetic construct either at a single site or in
multiple locations in the host genome. Agrobacterium-mediated
transformation, on the other hand, usually leads to insertions at a single
site in the plant genome. In either case, however, the site or sites are
fairly random. Because the effect of a gene on the whole organisms is
significantly governed by its location, the lack of control over location is
a significant cause of unexpected effects.

In terms of the location of genetic material in traditional
breeding, since it occurs between organisms that share a recent evolutionary
background, it involves the shuffling around of different versions (called
alleles) of the same gene. Furthermore, these genes are usually fixed in
their location on the chromosome by evolution. With GE, the genetic
insertion happens in unpredictable places which can lead to unpredictable
effects. Thus in this key regard, genetic engineering is more random than
conventional breeding.

A clear example of unpredictability was seen in an
experiment performed with Arabidopsis thaliana, a plant in the mustard
family that is frequently used for biological research (Bergelson et al.,
1998). The experiment compared several lines, one developed by conventional
breeding, and two by genetic engineering, that all exhibited the same trait
of herbicide tolerance. Researchers at the University of Chicago induced
herbicide (chlorsulphuron) tolerance (HT) into A. thaliana via a form of
conventional breeding called mutation breeding and via GE. In mutation
breeding, the researchers exposed an ecotype (or variety) of A. thaliana
(ecotype Columbia) to a chemical, ethyl methanesulphonate, that induces
mutations in genes. They then isolated individuals that had a mutant
version of the allele coding for the enzyme acetolactate synthase (Csr1-1)
which conferred resistance to chlorsulphuron. They isolated those
individuals (by spraying the plants with chlorsulphuron; only the resistant
ones survived) and backcrossed them to wild-type A. thaliana ecotype
Columbia for six generations. For the GE plants, they inserted the Csr1-1
gene using a certain vector and created two separate GE lines, i.e. two
separate transformation events. Each line contained insertions of the
Csr1-1 transgene at a single site.

A. thaliana is normally a self-pollinating species with very
low rates of cross-pollination. Thus, it was thought that there would be
virtually no gene flow to other individual A. thaliana plants and thus
virtually no risk of transgenes moving from engineered A. thaliana to
non-engineered neighbors. There were also questions as to whether there
were any ecological differences between conventional breeding and GE
versions. An experiment was designed to test these issues. The experiment
entailed planting 144 plantsoof which 25% were wild type, 25% contained the
HT gene via mutation breeding, and 50% contained the HT gene via GE (25%
from line 1 and 25% from line 2)oand then collecting about 100,000 seeds
from the wild-type plants and looking to see how many carried the HT gene,
i.e. to look at the per-plant outcrossing rate.

The results were quite surprising. The per-plant
outcrossing rate was 0.30% for mutant fathers (i.e. containing the HT gene
from mutation breeding) and 5.98% for transgenic fathers (i.e. containing
the HT gene from GE). Thus, transgenic A. thaliana were 20-fold more
likely, on average, to outcross than ordinary mutants (i.e. those derived
from mutation breeding). Further genetic investigation found that the
outcrossing rates in the two GE lines were very differento1.2% and 10.8%.
Thus, the two GE lines of A. thaliana demonstrated 4-fold and 36-fold higher
rates of outcrossing compared to traditional breeding. Since the HT gene
was the same, the differences between GE and mutation breeding appear to be
associated with the overall process of genetic engineering. The differences
between the two GE lines appears to be due to the difference in location as
to where the insertions happened, as the entire genetic construct was the
same. This experiment clearly shows that a difference exists between
conventional (including mutation) breeding and genetic engineering. In
essence, in the one GE line, the act of genetic engineering had transformed
a species that was normally an inbreeder to an out-crosser.

Another example of an unexpected effect that may have been
due to the location of the insertion occurred in an experiment with yeast
that involved adding not a transgene from another species but inserting
multiple copies of a naturally occurring yeast gene. In that experiment,
the scientists found that a three-fold increase in an enzyme in the
glycolytic pathway, phosphofructokinase, resulted in a 40-fold to 200-fold
increase of methyglyoxal (MG), a toxic substance which is known to be
mutagenic, depending on the yeast line. As the scientists themselves
concluded, "the results presented here indicate that, in genetically
engineered yeast cells, the metabolism is significantly disturbed by the
introduced genes or their gene products and the disturbance brings about the
accumulation of the unwanted toxic compound MG in cells. Such accumulation
of highly reactive MG may cause a damage in DNA" (Inose and Murata, 1995).
The position of the insertion could potentially explain why the same genetic
construct caused from a 40-fold to 200-fold increase in MG concentration,
depending on the different yeast transformation events.

Use of vectors designed to move and express genes across species and
ecological barriers

A third important way genetic engineering differs from
conventional breeding is in its introduction of genes that move and cause
expression of desired traits.

Since traditional (or conventional) breeding involves mixing
of genetic material from species that are sexually compatible/fertile, there
is no need for special genetic elements to facilitate this process; sexually
compatible species already contain such elements. The same is not true with
GE, which utilizes non-sexual means of reproduction and usually entails the
movement of genetic material between species that could rarely, or never,
exchange genetic material in natural conditions. To facilitate this
process, GE makes use of vectors specifically designed to move and express
genes across species and ecological barriers. These vectors consist of
genetic elements and sequences derived from efficient genetic parasites
(viruses, plasmids, mobile elements, etc.) and are specifically designed to
breach species barriers, i.e. to smuggle genes into cells that would
otherwise exclude them and get the genetic material inserted into the genome
of the host plant.

In microorganisms, plasmids are known to move readily
between bacteria. In crop genetic engineering, plasmids are invariably used
and are derived from the tumor-inducing plasmid (the Ti-plasmid) of the
bacterium Agrobacterium, as discussed earlier.

Genetic elements from Agrobacterium are never added to a
plant's DNA through conventional breeding, and are only see in the DNA of
other species in nature in plants infected with crown gall or hairy root
disease, in the infected cells.

Virtually all crop plants derived via GE also contain a
powerful promoter (a genetic regulatory or "on"-switch) from the Cauliflower
mosaic virus (the CaMV 35S promoter), which in nature causes a disease in
plants in the mustard family. Normally, genes in a plant have their own
promoters so that the gene will be turned on at the right time in
development and will be expressed at the right level, i.e. the right amount
of the desired gene product will be produced. A promoter from a plant virus
is used because viruses are genetic parasites that have the capability to
infect a plant cell and hi-jack its cellular machinery to make multiple
copies of itself in a short period of time. The CaMV 35S promoter is used
precisely because it is such a powerful promoter, which leads to
hyperexpression of the transgenes, having them be expressed at perhaps 2 to
3 orders of magnitude higher than of the organism's own genes. The CaMV 35S
promoter effectively puts the transgene(s) outside of virtually any
regulatory control by the host genome as the natural plant promoters for
each gene allow.

Thus, the use of a foreign promoter is needed in GE and is
not found in traditional breeding, including hybridization and wide crosses
and so constitutes a difference between GE and conventional breeding.
Indeed, for most of the genes that are being transferred (gene for herbicide
tolerance, gene for Bt endotoxin), if one used the naturally occurring
promoter for that gene, the plant would never be able to recognize the
inserted gene and express it. Thus, a promoter that works in plants must be
used; hence the reason for the widespread use of a plant viral promoter.
Most promoters that work in plants fail to get the gene expressed at a
high-enough level to do the work; hence the use of the CaMV 35S promoter
(the strongest of the various promoter in the CaMV).

Use of such strong promoters also raise safety concerns.
Since the CaMV 35S is so strong, not only can it affect the introduced
transgenes, it can also affect genes (either turn them "on" or turn them
"off") thousands of base pairs upstream and downstream from the insertion
site on a given chromosome and even affect behavior of genes on other
chromosomes. Consequently, depending on the insertion site, a gene that
codes for a toxin could be turned "on," leading to production of that toxin.

The potential of CaMV to turn genes "on" is of particular
concern because of what we are learning about how plants normally turn many
genes "off," through a phenomenon known as gene silencing. Gene silencing
appears to be a key defense against intrusion of foreign DNA, particularly
from disease-causing organisms, and also regulates normal gene expression.
In the last 5-10 years, scientists have come to realize that genetic
material can in fact move between organisms that are incapable of mating
with each other. Such lateral movement of genetic material is called
horizontal gene flow (vertical gene flow is the movement of genes from
parent to offspring), and occurs in nature more frequently than has been
assumed. Such horizontal gene flow is know to occur in microorganisms;
indeed, it is one of the main ways that antibiotic resistance or
pathogenicity is passed around among bacteria. Furthermore, numerous
viruses can insert themselves into host genomes.

Until recently, such horizontal gene flow was considered
rare or non-existent in plants. In 1998, scientists reported evidence that
genes from a fungus had invaded 48 out of 335 genera of land plants surveyed
and that such movement occurred on some 32 separate occasions (Cho et al.,
1998). They extrapolated these genes had invaded higher plants via
horizontal transfer over 1,000 times and that such a "massive wave of
lateral transfers is of entirely recent occurrence" (Cho et al., 1998:
14244). Just a couple of months ago, a paper in the November 19, 1999 issue
of the Proceedings of the National Academy of Sciences demonstrated that
sequences from a previously unidentified tobacco pararetrovirus had
repeatedly integrated themselves into tobacco chromosomes (Jakowitsch et
al., 1999). Prior to this study, plant viral sequences were thought to
integrate rarely, if at all, into host genomes.

The recognition that genetic material can move laterally
between species, along with the recognition in recent years that DNA is not
as fragile as previously thought and can persist for extended periods of
time in a variety of habitatsoaquatic, terrestrial, etc.ohas lead to
increasing research on the mechanisms that organisms use to prevent the
intrusion of foreign DNA. After all, since genomes are complexly regulated
wholes, work with other complex systems has shown that intrusion of new
elements can lead to destabilization of that whole. Indeed, normal
development in a plant requires an exquisite coordination of genes, with the
right set being turned on at the proper moment in development. The plant's
regulatory system should have a mechanism to ensure that unwanted
disruptions of such an elaborately coordinated system are prevented or

Such defenses have been found to exist, and consist of
pre-integration and post-integration (i.e. before and after the foreign DNA
has been incorporated into the host chromosome) mechanisms (Traavik, 1998).
The pre-integration mechanisms include preventing the DNA from entering the
cell or digesting the foreign DNA (with nucleases) that enters the cell.

The post-integration mechanisms consist of forms of "gene
silencing." Gene silencing was initially discovered in transgenic plants
and was initially thought to occur only in the case of transgenes. It is a
significant impediment to genetic engineering because it leads to
instability. A review of this topic in 1994 stated this succinctly:
"While there are some examples of plants which show stable expression of a
transgene these may prove to be the exceptions to the rule. In an informal
survey of over 30 companies involved in the commercialization of transgenic
crop plants, which we carried out for the purpose of this review, almost all
of the respondents indicated that they had observed some level of transgene
inactivation. Many respondents indicated that most cases of transgene
inactivation never reach the literature" italics added (Finnegan and
McElroy, 1994: 883).

Gene silencing can occur by preventing either transcription
(making a messenger RNA [mRNA] copy of a DNA sequence) or translation
(making a protein from the mRNA); the former occurs in the nucleus, the
latter in the cytoplasm. Hypermethylation of genetic material is one
mechanism associated with preventing transcription (Matzke and Matzke, 1995)
while formation of aberrant RNA molecules, with occasional DNA methylation,
is the main mechanism for posttranscriptional silencing (Scheid et al,

Indeed, transgene silencing is becoming a frequently observed
phenomenon. Although not completely understood, a number of factors have
been shown to affect transgene inactivation including insertion of multiple
copies of the transgene, hyperexpression of transgenes (e.g. due to use of
CaMV 35S promoter) and environmental factors (Srivastava et al., 1999).
High numbers of copies of the transgene and presence of multiple insertion
sites lead to a much higher incidence of gene instability. Since these are
characteristics of direct gene transfer methods, which are commonly used on
cereals, we should expect a higher probability of problems in such crops.

Perhaps the first, and most well studied, example of such unstable
transgene silencing was seen in work done in Germany with petunias that were
engineered with a single gene from corn to produce a new salmon red flower
color (Meyer et al., 1992). After transforming the petunias, the scientists
worked with a line that contained a single copy of the inserted gene at a
single insertion site (i.e. the most stable situation). Some 30,000
transgenic petunias carrying a single gene conferring the salmon red flower
color phenotype were grown outside and observed for differences. Initially,
the scientists were looking for mobile elements (so-called "jumping genes"
or transposons) that were naturally occurringosuch mobile elements would
"jump" into the color gene disrupting it and leading to a different
coloroand thought to occur at frequencies of 1 in a 100 to 1 in 100,000.
The unexpected result was the finding that significant numbers of the plants
were either weakly colored, white, had variegated colors or different
sectors of the flower being different colors. Since petunias produce up to
50 flowers over the course of the growing season, any changes in individual
plants can be easily seen. Furthermore, the number of non-salmon red
flowers increased during the season. At the beginning of the season, the
percentage of flowers with various color patterns were as follows: salmon
red, 91.6%, weakly colored, 7.6%, sectored colored, 0.3%, variegated, 0.2%,
and white, 0.3%. By the end of the season the figures were 37.6%, 60.9%,
1.1%, 0.2% and 0.2%, respectively. The change in color was linked both to
the age of the plant and to environmental circumstances as wellothere was a
three-week period near the end of the growing season with particularly hot
days and bright sun. Analysis at the molecular level revealed that the bulk
of the non-salmon red flowers exhibited methylation of the promoter (which
was the CaMV 35S) associated with the transgene.

This result, which was quite unexpected, clearly demonstrates that
the transgene are unstable and prone to being switched off or turned down.
It also demonstrates the important effect of the environment as the flower
color changed over time; by the end of the season over 62% of the flowers no
longer exhibited the full salmon red color. Thus, there appears to be
greater instability in the transgene expression over time, depending on both
the age of the plant and environmental conditions.

Since this study, more work on gene silencing has been done. The
newer work has also shown that "gene silencing" is not restricted to
transgenes, but is found to occur naturally under certain conditions. The
current scientific thinking is that gene silencing evolved for three
purposes: to regulate normal gene expression; to inactivate foreign DNA
that comes from pathogens; and to prevent genetic eventsosuch as movement of
"jumping genes" (transposons)owhich may disrupt the normal structure and
function of the genome. In an overall sense, gene silencing serves to
protect a genome from being disrupted by external or internal forces. Since
it serves as a mechanism for detecting and destroying foreign genetic
material, it's not surprising that gene silencing happens so frequently in
GE. Thus, for GE to work, the genetic engineer must use all sorts of
mechanisms to attempt to overcome the plant's natural defenses. That's the
reason for the use of powerful genetic elements from viruses (promoters and
enhancers), pathogenic bacteria, and mobile elements (e.g. transposons).

Given the inherent unstability of transgenes and the
phenomenon of gene silencing, which can be influenced by environmental
conditions, we would expect to see problems associated with transgene
stability in the field. The unpredictable influence of the environment may
explain what went wrong in Missouri and Texas with thousands of acres of
Monsanto's glyphosate tolerant cotton and Bt cotton, respectively. In
Missouri, in the first year of approval, almost 20,000 acres of this cotton
in malfunctioned. In some cases the plants dropped their cotton bolls, in
others the tolerance genes were not properly expressed, so that the GE
plants were killed by the herbicide (Fox, 1997). Monsanto maintained that
the malfunctioning (a result of gene unstability) was due to "extreme
climatic conditions." A number of farmers sued and Monsanto ended up paying
millions of dollars in out-of-court settlements. In Texas, a number of
farmers had problems with the Bt cotton in the first year of planting. In
up to 50% of the acreage, the Bt cotton failed to provide complete control
(a so-called "high dose") to the cotton bollworm (Helicoverpa zea). In
addition, numerous farmers had problems with germination, uneven growth,
lower yield and other problems. The problems were widespread enough that
the farmers filed a class action against Monsanto. Just a few months ago,
Monsanto settled the case out of court, again by paying the farmers a
significant sum (Schanks [plaintiffs attorney], personal communication).

Horizontal gene flow is the closest thing to genetic engineering in
nature. However it appears that only a limited number of microorganisms can
insert DNA into plants, and that plants have evolved defenses against this.
Further, each insertion is a one-time event, whereas with GE, rather than a
single mutant individual appearing, the environment is flooded with many
many transformed plants, containing DNA from sources that bacteria would
never naturally carry. Again, GE is a quantum leap from the natural
phenomenon. The simultaneous introduction of the CaMV promoter gene, to
override silencing, destanbilizes the engineered genome

Another significant differences between conventional breeding and GE
is the virtually ubiquitous use of marker genes that code for antibiotic
resistance. Such marker genes are needed to facilitate identification of
the fairly rare cases where genetic transformation has been successful. The
widespread use of genes that code for resistance to antibiotics raise the
potential question as to whether such genes be horizontally transferred to
bacteria rendering them resistant to the antibiotic in question.


Genetic engineering clearly differs from conventional
breeding in several ways. Conventional breeding relies primarily on
selection, using natural processes of sexual and asexual reproduction.
Genetic engineering utilizes a process of insertion of genetic material, via
a gene gun or other direct gene introduction methods, or by a specially
designed bacterial truck, which does not occur in nature. Genetic
engineering can insert genetic material from any life form into any other;
conventional breeding generally can only work within a species, or at most,
within closely related genera, as when they do wide crosses. Conventional
breeding relies on mixing characteristics from different populations within
a species and then selecting from a plants natural complement of genetic
elements. However genetic engineering relies on inserting genetic elements,
and they end up in random locations, which can disrupt complex gene
interactions. Many of the products exhibit unexpected effects.

Genetically engineered plants almost always contain a viral
promoter gene, the "on"switch for the gene inserted; genetic material from
Agrobacterium, which facilitates transfer of the genetic construct into a
plant's genome; and in most cases a bacterial antibiotic marker gene. These
are never deliberately introduced in products of conventional breeding.

There are thus key identifiable scientifically documentable
differences between genetic engineering and conventional breeding, both in
the process, and in the genetic makeup of the product. Indeed, in any
situation in which DNA is recoverable, the presence of engineered DNA can be
identified in the product.

Whether these differences are "significant" or
"insignificant", however, is a value question and a philosophical question,
not a scientific question. We see genetic engineering as a quantum leap
from conventional breedingoas different from it as nuclear power generation
is from a coal-fired plant. In our view traditional breeding is humankind's
attempt to manipulate natural breeding processes for our own benefit. But
this attempt, while wildly successful in one sense (the creation of all the
major crop plants from weedy wild relatives), has only mildly pushed the
barriers of genetic material transfer. GE, on the other hand, does away
with all such barriers in the natural world, permitting scientists to
manipulate genetic materials in a way that was inconceivable before.

A number of scientists, particularly ecologists, see the
differences as we do. However other scientists, particularly molecular
biologists maintain it is a continuum. In the end, it is a matter of
values, judgment and opinion as to who is correct. While science can inform
this debate, this is not a question science can answer. Indeed, it can well
be argued that there is no one right answer as to whether this difference is
"significant" or not.

In terms of a FDA decision about labeling, this debate about
how "significant" the difference is should be irrelevant. If there is a
documentable difference between two foods, or two processes, and consumers
care about the difference, then under the Food Drug and Cosmetic Act FDA has
the authority to require labeling and should do so. It does not matter if
it is a small difference or a large difference. Nor does it matter whether
consumers are "right" or "wrong" to care about this difference.

Labeling would not be a deviation from previous FDA policy.
Indeed, the failure to require labeling is a deviation from previous FDA
policy. The difference between frozen peas and fresh peas, one could easily
argue, is much less than the difference between genetically engineered peas
and conventional peas. The frozen and fresh peas can be genetically
identical. The frozen peas may even be nutritionally superior, even as
consumers choose fresh peas thinking fresh is better. Yet FDA appropriately
requires labeling about the difference, and allow consumers to make their
own choices about what to buy, even if those choices are a "mistake",
leaving it to the marketplace to educate consumers about pluses and minuses
of each type of product. It should do the same for any food produced by,
or derived from food produced by, a process that inserts genetic material
using a gene gun, a specially-designed vector, or a comparable method.

Additional reasons to label include helping consumers manage
food allergies and sensitivities and allowing the public health community to
track and identify any unexpected effects. These are discussed in more
detail in Consumers Union's comments to FDA on Docket No. 99N-4282.

The science is also clear that this unique and identifiable
process of genetic engineering creates a new and unique potential for
unexpected effects, due to the unique nature of the material being
inserted, from a genome which has not previously interacted with the host
genome, due to lack of control over the location at which the gene is
inserted, and due to the introduction the CaMV "promoter" gene, which
overrides the existing genetic programming. FDA therefore has an
obligation to require mandatory reviews of all genetically engineered food
before it goes on the market, and develop ways to screen for unexpected
effects which could have health consequences.

There are also predictable risks, such as potential risks of
toxins, allergens and nutritional changes and antibiotic market genes, which
FDA should address. These are discussed further in our comments to the

The details of what that safety review entails should be
developed through a further process of notice and comment.


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