Scrambling and Gambling with the Genome
By Jeffrey M. Smith, author of Seeds of Deception
Advocates of genetically modified (GM) food often use this popular analogy:
"With genetic engineering, transferring genes from one species‘ DNA to
another is just like taking a page out of one book and putting it between the
pages of another book."
The words on the page of their hypothetical book are comprised of the four
letters, or molecules, of the genetic code, which line up in "base pairs"
along the DNA. The inserted page represents a gene, whose code produces one
or more proteins. The book is made up of chapters, which represent chromosomes-large
sections of DNA.
The analogy makes the process of genetic engineering appear to be as simple
and precise as inserting a new page.
Is It Really That Simplistic?
A groundbreaking report, however, shreds the book analogy. Written by three
UK scientists and published in Biotechnology and Genetic Engineering Reviews,
it reveals that the process of genetic
engineering results in widespread mutations-within the inserted gene, near
its insertion, and in hundreds or thousands of locations throughout the genome.
And these mutations are overlooked by many scientists and regulators. 
The report is an extensive review of research that overturns the central arguments
by biotech advocates-that the technology is precise, predictable, and safe,
and that current studies are adequate. As it turns out, these arguments are
not true at all. On the contrary, this report demonstrates that GM crops represent
a significant gamble to public health and the environment (see www.econexus.info).
Gene Insertion Methods Create Absurd Changes
There are two popular methods for creating GM crops. Both create mutations.
The first method uses Agrobacterium-bacteria that contain circular pieces
of DNA called plasmids. One section of this plasmid is designed to create tumors.
Under normal conditions, Agrobacterium infects a plant by inserting the
tumor-creating portion into the plant‘s DNA.
Genetic engineers, however, replace the tumor-creating section of the plasmid
with one or more genes. They then use the altered Agrobacterium to infect a
plant‘s DNA with those foreign genes.
The second method of gene insertion uses a gene gun. Scientists coat thousands
of particles of tungsten or gold with gene sequences and then shoot these into
thousands of plant cells.
Years ago, sequences that were shot into cells included genes intended for
transfer (gene cassettes) as well as extraneous DNA from the plasmid, used for
creation and propagation of the cassettes in bacteria. These days, many scientists
take the added step of removing the extraneous, mostly bacterial DNA, and coat
the particles with just the cassette.
Scientists speculate that both methods trigger wound responses in the plant
cell, helping its DNA integrate the foreign gene. Only a few cells out of thousands
incorporate the "foreigner" with the gene gun technique.
Per the book analogy, a single, intact, foreign page (gene) is inserted. That‘s
the intention anyway.
In reality, most transformed DNA end up with many copies of foreign genes,
or partial genes and/or gene fragments. Sections of inserted genes are commonly
changed, rearranged, or deleted in the insertion process. Plus, extraneous pieces
of plasmid DNA sometimes intermingle in and around the inserted gene, or scatter
throughout the genome.
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Mutations Near the Site of Insertion
Besides changes made in the inserted material, sections of the plant‘s DNA
near the insertion site are frequently messed up in some way. This effect, called
insertional mutagenesis or insertion mutation, has been known for years. But
it wasn‘t until 2003 that a large-scale systematic analysis was conducted.
Researchers looked at insertions into 112 Arabidopsis thaliana plants-a species
used often in plant research.  Although the study may not accurately reflect
what happens in edible crop plants, it is the only large study at this point.
Selected plants had single copies of the foreign gene, inserted with Agrobacterium.
Eighty of the 112 plants (71%) developed small mutations near the insertion
site. Mutations included deletions of 1-100 base pairs and/or insertions of
1-100 extraneous base pairs. Inserted sequences came from the foreign gene,
extraneous parts of the plasmid, or other parts of the plant‘s DNA.
The remaining 32 plants (29%) acquired large scale insertions, rearrangements,
duplications and/or deletions. In two plants, parts of whole chromosomes broke
off and translocated into another section of the DNA.
Another study using the same plant species also found that a section of DNA
at least 40,000 base pairs long translocated from one chromosome to another.
That long section actually duplicated itself, since it was also found intact
in its original position.  A third study identified a deletion of 75,800
base pairs, which probably contained 13 genes. 
As stated, the above studies used the Agrobacterium insertion method. Astoundingly
few studies analyze insertion mutations with the gene gun method. But the conducted
research consistently demonstrates large scale disruptions of the DNA.
According to the Econexus report, "The vast majority of insertion events
created via particle bombardment [gene gun] are extremely complex, with multiple
copies of transgenic DNA inserted at a single insertion-site."1 They contain
large amounts of extraneous DNA, multiple fragments of the foreign gene, and/or
small or large fragments of plant DNA interspersed with the inserted genes.
In one study, scientists found 155 separate breaks indicating recombinations
of the inserted genetic material. 
As per the Econexus report, in rare cases where only a single copy of the foreign
gene is inserted, they still "turn out to contain fragments of superfluous
DNA and/or they appear to be associated with large deletions and/or rearrangements
of the target plant DNA."
One study on gene gun insertion revealed that DNA of an oat plant contained:
The full sequence of the foreign gene plasmid
A small stretch in which oat DNA was mixed up with foreign plasmid DNA
A partial copy of the plasmid, plus
Another section with oat and plasmid sequences scrambled together.
Analysis also indicated that the plant‘s DNA on either side of the insertion
contained rearrangements or deletions. And, there were two other insertions
elsewhere in the DNA. One contained a rearranged section of the plasmid (296
base pairs), scrambled plant DNA on either side, and the deletion of 845 base
The study employed DNA sequence analysis, the most thorough method for evaluating
insertion mutations. In practice, it is rarely used.
Instead, genetic engineers traditionally rely on the less precise Southern
blot test, which picks up only major changes in DNA sequence. When this test
was applied to the oat DNA above, it indicated the presence of only a single
intact inserted gene, and failed to identify two other insertions and all the
mutations and fragments.
So on the whole, biologists who create GM plants have no idea of the extent
to which their creations may produce unintended side effects due to scrambled
"Location, Location, Location" -- Not Just True in Real Estate
Neither gene insertion method is able to "aim" the foreign gene into
a particular location in the DNA. Furthermore, scientists rarely conduct experiments
to find out where exactly the inserted genes end up.
But in the real estate of the DNA, location is vital. The functioning
of the foreign gene can change dramatically depending on where in the genome
it is located. The side effects of gene insertion can be significantly influenced
by location as well.
Although only an estimated 1-10% of plant DNA makes up the genes, Agrobacterium
insertions end up inside functioning gene sequences 35%-58% of the time. (The
percentage for gene guns is unknown.) Genes are also inserted in other areas
that influence gene expression. In either case, insertions can significantly
disrupt the normal functioning of the plant‘s genes.
One reason insertions end up inside genes so often is that for the foreign
genes to function, they need to locate in the regions of the host DNA that are
"active," that allow for gene expression. To learn which inserted
genes end up in active portions, scientists typically add an antibiotic resistant
marker (ARM) gene to the genetic cassette.
After insertion, scientists apply antibiotics to all the cells to kill those
without a functioning ARM gene in their DNA. Since the active region of the
DNA is also where the plant‘s functioning genes are located, those that survive
this selection process are more likely to have foreign genes lodged inside the
Mutations All Over the DNA Landscape
Once genes are inserted into a plant cell‘s DNA, scientists typically grow
the cell into a fully functioning plant using a method called tissue culture.
Unfortunately, this artificial method of plant propagation results in widespread
mutations throughout the genome.
In fact, tissue culture is sometimes used specifically to create mutations
in plant DNA. These mutations can influence the crops‘ height, resistance to
disease, oil content, number of seeds, and many other traits. ,
Genetically modified cells that undergo tissue culture can have even more mutations
throughout the genome than cultured non-GM cells. It is unclear why gene insertion
has this effect, but scientists speculate that it may, in part, come from unsuccessful
insertions or insertions of small fragments.
The process of gene insertion combined
with tissue culture typically results in hundreds or thousands of mutations,
including small deletions, substitutions, or insertions in the genetic code.
The changes are vast. Two studies suggested that 2-4% of the genome of a GM
plant was different than non-GM controls.,
Furthermore, estimates are based on detection methods that miss many mutations
such as short deletions and insertions and most base pair substitutions. Thus,
the actual degree of gene disruption is probably greater.
These genome-wide mutations are found in every GM plant analyzed. Astoundingly,
these types of mutations are not even evaluated in commercially released GM
If the original GM plant is crossed (mated) with other lines repeatedly, many
of these small, genome-wide mutations are corrected. It is unknown, however,
how many mutations still persist in food crops. And the propagation of certain
species, like the GM potato that was on the market years ago, probably did not
undergo any outcrossing. So it is likely to contain all of the mutations created
during insertion and tissue culture.
The Serious Consequences of Mutations
Mutations and extraneous insertions carry risk. They can permanently turn genes
on or off, alter their function, and/or change the structure or function of
the protein that they create.
A single mutation can influence many genes simultaneously. The insertion process
Cause the over-production of toxins, allergens, carcinogens, or anti-nutrients
Reduce the nutritional quality of the crop
Change the way that the plant interacts with its environment.
Because of our limited understanding of DNA, even if we knew which parts were
disrupted, we don‘t necessarily know the consequences.
In addition, the insertion of bacterial plasmid DNA into plant DNA creates
another serious risk.
Similarities in the genetic sequence between the plasmid and the DNA of human
or animal gut bacteria or soil bacteria might significantly increase the likelihood
of horizontal gene transfer -- meaning that plant genes may transfer into the
DNA of the soil or gut bacteria.
The only human feeding study on
genetic engineering confirmed that the genes inserted into GM soybeans do transfer
into the bacteria inside human intestines.
Advocates of biotechnology often defend the safety of their products by claiming
that modern methods of plant breeding other than genetic engineering are used
on a wide scale, have a history of safe use and create comparable mutations.
The Econexus report reveals that everything about this argument is pure speculation
and is not supported by scientific literature. There is no evidence
that these modern methods are used widely, are consistently safe, or create
mutations of the same kind or frequency as genetic engineering.
In reality, many biotech scientists are unaware of the massive quantity of
mutations that are generated by the GM transformation process (gene insertion
and tissue culture).
In fact, the regulatory agencies that approve GM foods operate as if the insertion
process has no impact on safety. , They don‘t require extensive evaluation
of the mutations. Therefore the extent of these in approved GM food crops has
not been identified.
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The few studies that were conducted revealed many significant problems. GM
varieties contain truncated or multiple fragments of the inserted gene and extraneous
or scrambled DNA. The protein produced by the foreign genes can also be truncated,
altered, or fragmented.
Many significant differences between GM and non-GM crops have been observed,
which may result from the insertion process.
An approved GM squash, for example, contains 68 times less beta-carotene
and four times more sodium than non-GM squash.
One GM corn variety contained a fragment from a gene that was supposed
to be inserted into a different GM variety.
GM soybeans have much higher levels of a potential allergen and anti-nutrient.
But GM crops are tested for only a handful of nutrients or known toxins,
and therefore the true impact of gene mutations is not known.
Furthermore, GM plants are grown in huge
quantities. Undetected alterations may result in harm to the environment or
human health on an unprecedented scale. With so little known about the impact
of gene insertion and with so much at risk, applying genetic engineering to
food and crops is a huge gamble.
Let‘s Revise That Book Analogy, Shall We?
With genome scrambling in mind, let‘s revise the book analogy as follows:
The DNA is like a large book with the letters consisting of the four molecules
that make up the genetic code. Located throughout the book are special one-
to two-page passages, called genes, which describe characters called proteins
(including enzymes). The book is divided into chapters called chromosomes.
When a single foreign page (gene) is inserted through the process called genetic
engineering, the book goes through a profound transformation.
There are typos throughout, in hundreds or thousands of places.
Letters are switched here and there.
Words and sentences are scrambled, deleted, repeated or reversed.
Long and short passages from one part of the book may be relocated or
repeated elsewhere, and bits of text from entirely different books show
up from time to time.
As you get close to the inserted page, things get really strange. The
story becomes indecipherable. The text includes random letters and sections
of inserted foreign text, and several pages are missing.
The inserted page may actually be multiple identical pages, partial pages,
or small bits of text.
Sections are misspelled, deleted, inverted, and scrambled.
As a result of changes in the story line throughout the book, several characters
(proteins) act differently, sometimes switching roles from heroes to villains,
or vice versa. It all makes you wonder about the comment made by the biotech
advocate as he handed you the volume, "It‘s just the same old book, only
with a single page added."
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Jeffrey M. Smith is the author of the new publication Genetic
Roulette: The Documented Health Risks of Genetically Engineered Foods,
which presents 65 risks in easy-to-read two-page spreads. His first book, Seeds
of Deception, is the top rated and #1 selling book on GM foods in the
He is the Executive Director of the Institute for Responsible
Technology, which is spearheading the Campaign for Healthier Eating in America.
Go to www.seedsofdeception.com
to learn more about how to avoid GM foods.
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© Copyright 2005 by Jeffrey M. Smith. Permission is granted
to reproduce this in whole or in part.