GEO Watch | Scientists analyze threats posed by new GMO technology, RNAi

Adhominal | Courtesy of Space Collective

Moderator’s Note: The last time I
reported on emerging genetic engineering (GE) technologies, the Monsanto Co.
had just revealed it was working on a third generation technology based on
microRNA – please see the post of August
6, 2014. Now, Monsanto and other ‘Gene Giants’ are a step closer to
implementing use of RNA interference as a way to solve persistent and worsening
problems associated with evolving resistance by pests and weeds to their
current GMO Bt and herbicide resistance technologies.

All this is being done – no surprise – without independent third
party scientific assessment of environmental and human heath risks. I am
reposting an important analysis of the risks posed by RNAi as seen through the
lens of three scientists who are respected colleagues in their fields – Dr.
Jack Heinemann, Judy Carmen, and Dr. Sarah Agapito.

The technology operates on the basis of a “gene silencing”
interference protein that can be sprayed or engineered into the plant. As the
authors note:

Double-stranded RNAs can “silence” genes. For example, a small
double-stranded RNA molecule has been developed based on a fragment of the dvsnf7 gene.
This can kill western corn rootworms when the molecule is added to their food,
or when it is expressed (by GM) in the corn plants, which the worms eat.

This technology, the authors further suggest, has not been
adequately studied or understood and the human health implications could be
quite serious.  As the authors further
conclude:

Double-stranded RNA produced in plants can be taken up by people
through food, as shown in studies last year. Insects also take up RNA through
food, which is why manufacturers are patenting dietary-based insecticides.

Once again, the EPA (Environmental Protection Agency), the USDA
(US Department of Agriculture), and the FDA (Food and Drug Administration) are
failing to evaluate and curb the deployment of these technologies without an
adequate predictive ecology of their potential impacts. This technology is so new and untested that the Obama Administration as created a review panel to develop recommendations on how to evaluate risks.

This brief but insightful analysis was originally published on April 15, 2013 in The
Conversation, a blog on science and technology musings by scientists
and known for its “academic rigor with journalistic flair”. It is shared by
that sites Creative Commons license, and all readers and followers can repost
without direct permission but with acknowledgement of the source.

Securing the safety of
genetic modification

Jack HeinemannProfessor of Molecular Biology and Genetics at University of
Canterbury Judy CarmanAdjunct Associate Professor, Health and the Environment at
Flinders University Sarah AgapitoPhD Student at Universidade Federal de Santa Catarina

Most genetically modified (GM) crops are based on moving DNA from one organism to another to
introduce a new protein. Now a growing number of genetically modified crops are
based on intentionally changing RNA.
However this new technology may prove to be risky business.

Ed Kwong artwork courtesy of Cargo Collective

RNA world

RNA or ribonucleic acid is the neglected stepsister of DNA, but
it is quickly becoming the Cinderella of biotechnology.

DNA (deoxyribonucleic acid) is the material basis of the genome
of most organisms, it’s what encodes our genes. RNA is the second stage of a
process that produces proteins in cells. It’s the messenger and is normally
single-stranded. However, when it’s double-stranded, RNA is sometimes also a
molecule that can turn genes on off.

The RNA molecules used in genetic modification are known as
double-stranded RNAs. These RNA molecules are already being explored for a
number of uses.

A number of companies are planning to engineer plants with
double-stranded RNAs to kill pests. Some are also planning to make sprays that
carry RNA into the cells of weeds.

Double-stranded RNA is being tested as a feed supplement to make
bees resistant to viruses, or to kill bee mites.

And GM plants with nutritional characteristics altered through
the introduction of novel double-stranded RNAs are already being grown for the
human food supply.

RNA: the “new DNA” of genetic modification

Most traits in existing commercial genetically modified
organisms are due to the introduction of one or more proteins by modifying DNA.
But new modifications are based on the double-stranded RNA molecules that
regulate production of proteins.

Double-stranded RNAs can “silence” genes. For example, a small
double-stranded RNA molecule has been developed based on a fragment of the dvsnf7 gene.
This can kill western corn rootworms when the molecule is added to their food,
or when it is expressed (by GM) in the corn plants which the worms eat.

Although the mechanisms for this are still being described,
there are already a number of GM crops based on this principle. It is also
probable that all commercial GM crops produce unintended regulatory RNA
molecules that have not been tested as part of the routine risk assessment.

Worse, one double-stranded RNA can produce unintended secondary
RNA molecules that have different sequences and therefore potentially different
targets. These can arise in the modified plant or in the cells of those who eat the modified
plant.

Not just food: double-stranded RNA
(dsRNA)

is already used in other consumer
products.

Image source: http://www.larifans.lv/en/    

We are concerned that what happens to pest insects and nematodes
that eat these RNA molecules can also happen to other insects, wildlife and
people. An increase or decrease in cell proteins can have important effects on
our health. These effects vary depending on the protein, and the cells, organs
or tissues to which the double-stranded RNA is delivered.

Small changes in the DNA sequence can change the spectrum and
number of potentially affected genes. That is why in our view a risk assessment
needs to consider each novel RNA created specifically, whether
deliberately or inadvertently.

Risk assessment

The risks of double-stranded RNA have not been systematically
evaluated by any regulatory agency we know of, and there are no standard safety
testing procedures.

In a recent issue of Environment International we published peer-reviewed research looking at risk
assessments done by three different regulators affecting three countries. In
all cases the regulators didn’t assess the risk of new double-stranded RNA molecules.

In Australia and New Zealand, a genetically modified plant is
subject to an environmental risk assessment if it is to be used in a field
trial or released for cultivation. A food safety assessment if it is to be used
in food or animal feed.

Food Standards
Australia New Zealand assesses GM plants that are safe for use as
food. Seven plants approved by Food Standards have been deliberately modified
to produce double-stranded RNAs.

Various GM wheat varieties have been assessed for field trial by
the Australian Office of the Gene Technology
Regulator. These use the same double-stranded RNA technology.
Neither regulator, to our knowledge, has assessed a GM plant for unintentionally
created double-stranded RNAs.

Exposure incorrectly assessed

Double-stranded RNA produced in plants can be taken up by people
through food, as shown in studies last year. Insects also take up RNA through
food, which is why manufacturers are patenting dietary-based insecticides.

In another study a naturally produced double-stranded RNA was
found to alter gene
expression in mouse livers. Double stranded RNA could also alter
gene expression in human tissue culture cells.

Until now regulators have rejected the possibility that people
can be exposed to double-stranded RNA through food. There has therefore been no
research into the safety of these molecules. In short, regulators avoid
assessing potential safety issues by saying there were no risks to start with.

Were the regulators right but for the wrong reasons?

Various commentators
have argued since RNA is already in the food we eat, it must be safe. Without
evidence this reasoning is far from reassuring.

Only a small number of plants have been bred with intended
changes to double-stranded RNA. And most of these have been withdrawn from
sale, are not grown on commercial scales, or are in boutique crops such as
Hawaiian papaya.

The amount of these RNAs in food now is unknown but is probably
very small. Thus the argument of safety from existing experience is, at best,
speculative. And it fails to account for unintended double-stranded RNAs.

If there are no experiments, we won’t know if double-stranded
RNAs have an adverse impact or no impact. While we test food to some extent,
there are no studies of other important sources of exposure such as inhalation.
And critically, these studies are not on humans: even small differences between
our genomes and those of the animals used in tests might have large
consequences.

If we are to safely produce products that might contain novel
double-stranded RNA molecules, there needs to be routine bioinformatics and transcriptomic
testing.

The
power of RNA should be used for the betterment of all. On the way, it should
not become the snake oil of the 21st Century or the cause of avoidable
catastrophes.