dsRNA: silencing regulation

July 2013

Photo from Creative Commons by CIMMYT on Flickr

If you've just read RNA-MODIFIED FOOD - July 2013, you'll be aware that this latest GM development carries some serious new risks.

This latest GM fad doesn't introduce novel genes or proteins but creates much trickier transgenic regulatory RNA elements.

Now, you may be wondering whether our regulators are awake to the problems?

Lip-service is frequently paid to the 'precautionary principle', but rarely backed up by action. The prevailing regulatory culture seems to be one in which marketing of novel materials is encouraged to proceed until some proof of harm emerges. Scientific uncertainty is not used as a reason to delay their launch.

GM crops with novel dsRNA have already been approved despite ignorance about the mechanism of their action. For example, the first ever commercial GM crop, the FlavSavr slow-ripening tomato, was discovered many years later to have a dsRNA at the basis of its trait, and more recently a viral-resistant soya has been approved despite the admission that the dsRNA present arises “via a pathway that is still not understood”.

The first stage in all risk assessment is the identification of the hazards. A recent evaluation of the regulation of products containing dsRNA by an international team from New Zealand, Australia and Brazil, concluded that the present approach fails to carry out this first, vital, stage. Examples are described of how the risks have been either identified and then systematically denied, or, have simply never been acknowledged to exist. The need to deal with the risk of unintended side-effects has been routinely side-stepped by using assumption-based reasoning in lieu of scientific evidence.

The first assumption about the risk of dsRNA is that all RNA can be treated as a homogeneous class of chemicals. This enables all RNA to be considered GRAS (generally recognised as safe) because it has always been present in all food and therefore cannot intrinsically raise safety concerns.

Since RNA exists in a multitude of forms, some of which are highly (and catalytically) active, this first assumption derives from a wild and unacceptable generalisation. Like DNA, it is the chemical sequence of the RNA molecule which is responsible for its actions, not its chemical type: like artificial DNA, artificial dsRNA is introduced precisely because of the unique properties of the engineered sequence. Put another way, the sequence has been specifically designed to interfere with normal activity in the cell. In the food plant there could be accompanying, unintended interference which could create novel toxins and allergens, and in the consumer, unintended interference could cause disease.

Despite the obvious absurdity of the reasoning, the assumption that dsRNA is GRAS has even been used to give engineered insecticidal dsRNA a positive risk assessment. The implications of the fact that the sequence had been chosen specifically to damage animal cells was simply ignored.

Other assumptions used to trivialise the risks of dsRNA include the notion that any unintended action in the consumer would be 'transient' in nature (bear in mind that in a staple crop, this 'transient' action would happen every day), and the entrenched view that commercial feeding studies showing acceptable feed conversion rate and animal weight gain in livestock are somehow adequate as a safety test for humans (bear in mind the minimal life-length of all livestock, the heavy use of drugs to keep them 'healthy', and relative rarity of any chance to reproduce).

OUR COMMENT

Watch out for attempts to sneak these RNA-modified plants into your diet as 'non-GM'!

Because the transformation needed to generate dsRNA doesn't involve 'genes' or produce a specific novel protein, it's likely that the products of this technology will fall through regulatory loopholes. At the moment, there's no sign of any regulatory will to close the gaps. That means it's up to the public to create the will to regulate before that 'proof of harm' emerges to force the issue the hard way.

SOURCE:

• 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