RNA-modified food

July 2013

Image of biotechnology from Creative Commons / United Soybean Board on Flickr

Up until now, all major commercial GM crops have been created by inserting artificial genes. 'Genes' are stretches of DNA (see definitions below) which the cell uses to create specific proteins.

So far, the novel proteins in GM crops have fallen into only two categories: they have either been enzymes which confer tolerance to a weed-killer (such as 'Roundup'), or have been analogues (adapted look-alikes) of bacterial proteins (such as 'Bt') which kill crop pests.

'New' GM crops now entering the market are simply an extension of these older ones: they have been 'stacked' with combinations of the same genes. Typical biotech crops available to farmers have tolerance to more than one herbicide, and produce several different insecticides.

COMMENT This sort of GM tactic will, ultimately, be self-limiting. Accelerated weed-tolerance to the favoured herbicides, accelerated insect-resistance to the novel insecticides, and constitutional constraints on how much foreign protein a plant can be made to churn out while remaining healthy will make it unsustainable.

However, genes, Roundup-resistance and Bt insecticides are old-hat. Biotech science has moved on.

Genetic engineers have turned their attention away from creating genes and novel proteins, to the much more vast field of non-gene DNA.

DNA which doesn't have a direct role in protein synthesis plays a very major role in directing operations in the cell. To do this, such DNA produces short stretches of chemically-related 'RNA' (see definitions below) referred to, collectively, as regulatory RNA.

Regulatory RNA consists of a host of relatively small molecules which come in a huge variety of sizes, nucleic acid sequences, configurations, reactivity and changeability. They're active in all fundamental cellular processes, and can be catalytic in action (tiny amounts can induce extensive changes). They pass easily from cell to cell, potentially spreading throughout the organism no matter where they're first formed. Their functions (so far identified) are to control and co-ordinate DNA expression, protein activity, and each other; in other words they determine what happens when and where in the cell. It can be self-replicating and can create other forms of RNA. The actual active RNA molecules produced in cells vary with cell type, cell maturity, exposure to infection, environmental insults etc. To add an even more interesting dimension to this picture, the majority of RNA molecules don't follow the 'rules' of DNA/RNA chemistry you'll find in textbooks. 

RNA Interference (RNAi)

If you're interested in the mechanisms of this complex system here's a useful animation.

(Or you can view it at http://www.nature.com/nrg/multimedia/rnai/animation/index.html)

Growing interest has focused on one particular configuration of regulatory RNA. This has stretches which are paired up with complementary RNA sections, and is therefore referred to as 'double-stranded' RNA, or 'dsRNA'.

The dsRNA molecule is stabilised by its double-strand. It may have active regions or may be converted to an active form. In its active form it can react with complementary areas of DNA making the DNA unable to function. If the DNA is a gene, the gene will be 'silenced'. Note. dsRNA can also activate genes

Gene-silencing technology has already been used, for example, to delay ripening in fruit by blocking a key gene in the ripening process, or to combat plant viruses by blocking a key gene in viral replication, or to alter plant oil composition by blocking a key gene in the synthesis of undesirable oil types. There's a huge commercial potential in such novel crops.

There's also an enormous potential for harmful by-products and side-effects.

In the plant, there's every likelihood that lab-made dsRNA will find complementary areas to disrupt on other DNA and RNA molecules besides the gene it's supposed to silence. This means novel toxins and allergens could arise in food, and such a crop with novel materials could be susceptible to pathogens and pests never seen before.

There's no reason for a novel dsRNA made by a plant to be active only in plants just because it was produced by one. Moreover, even if the dsRNA is produced in a part of the plant not harvested for food, it can easily spread systemically and end up in the parts eaten.

dsRNA can resist cooking and digestion. It is known to circulate in the bodies of animal and human consumers. Inside a cell, there's every likelihood it will find complementary areas on RNA or DNA molecules to disrupt. Silencing of one of our vital genes or biochemical pathways could have lethal consequences, especially in children. Unhealthy changes in our gut flora would be likely first side-effect.

Just to add to the problem, science is showing that unintended and unpredictable novel dsRNA can arise in any organism whose DNA has been disrupted by old-fashioned genetic transformation. In fact, many GMOs ultimately fail because they generate dsRNA to neutralise the foreign DNA.

OUR COMMENT

If you thought GM food was a threat to your health, things just got a whole lot worse.

The potential for disease and heritable genetic changes in humans and animals fed novel dsRNA, and for sudden and catastrophic crop failure in plants producing novel dsRNA is not only huge, it's completely unpredictable. Only long-term and very detailed scientific feeding studies will reveal such problems.

The safety-testing needed for RNA-modified food is exactly the same at that need for protein-modified food, and any other novel food coming out of the lab.

It's time to demand the development of meaningful and comprehensive testing protocols: these must be long-term, multi-generational, include all major tissues and organs, must check for endocrine effects; they must then be followed up with clinical studies and a realistic system for monitoring the consuming population.

Definitions:

• DNA is a chain of various nucleic acid (NA) molecules attached to a back bone of deoxyribose (D) molecules.
• RNA is like DNA except that the back bone is ribose (R)
• The biological action of DNA and RNA lies in the sequence of the different kinds of nucleic acid molecules it contains

SOURCES:

• Jack A. Heinemann et al., 2013, A comparative evaluation of the regulation of GM crops or products containing dsRNA and suggested improvements to risk assessments, Environment International 55
• Jack A. Heinemann, Evaluation of risks from creation of novel RNA molecules in genetically engineered wheat plants and recommendations for risk assessment, Expert opinion, 28.08.12
• Judy A. Carman, Expert Scientific Opinion on SCIRO GM Wheat Varieties, September 2012
• Sandra Finnie, Scientists want assurances new GMO is safe, Straight Furrow, 4.04.13
• Dr. Mae-Wan Ho, RNA Interference “Complex and Flexible”, Institute of Science in Society Report, 22.05.13
• New GM technique not assessed for safety: dsRNA, GM Watch 21.03.13
• Dr. Mae-Wan Ho, New GM Nightmares with RNA, Institute of Science in Society Report, 29.04.14