Beware non-genetic engineering!

November 2011

The Human Genome. Picture from Wikimedia Commons
The foundation of commercial GM technology is the concept that one gene gives rise to one protein. A gene is a precise sequence of DNA which forms a 'blueprint' for the creation of a protein. DNA expresses itself by producing a precise sequence of (chemically-related) RNA. RNA provides the 'blue-print' for the manufacture of the protein after which it is quickly destroyed. From a regulatory point of view, DNA per se can't possibly be harmful unless it expresses itself, RNA per se can't possibly be harmful because it disappears, and the protein can easily be manufactured and safety-tested in isolation.

By ignoring the inconvenient layers of complexity at all levels of DNA expression, the biotech industry has exploited this simplistic model very lucratively. In particular, the industry has exploited ignorance. In a living cell, the genes form only some 2% of the total DNA. Ignorance about the function of all the remaining DNA was dealt with by pronouncing it 'junk'.

The unlikelihood of a cell wasting so much of its resources to create unnecessary 'padding' was simply set aside.


More recently, the first major level of complexity surrounding DNA expression began to be unravelled. 'Junk' DNA produces short RNA sequences which interact in various ways with the RNA-protein manufacturing process. Added to this was the discovery that plants have a biochemical mechanism to amplify the production of short RNAs to make multiple copies available.

The discovery of short RNAs made the one-gene-one-protein model a nonsense, but nevertheless biotech industry eyes lit up at the discovery. Here was a way of switching off genes in a crop plant! A door opened to a host of possibilities: unwanted components such as allergens and natural toxins could be avoided by knocking a single gene, desired components such as nutrients or useful industrial materials could be persuaded to accumulate by knocking out a single gene, male-sterile plants for hybrid breeding could be created by knocking out one of the genes needed for pollen production. Better still, plants could be designed to generate short insect RNAs designed to disable vital insect genes and kill pests.

The beauty of short RNA engineering for industry was quickly grasped. Their production wouldn't entail the energy-drain on the GM crop plants which has bedeviled the generation of artificial proteins. PR problems which have consistently dogged genetic engineering could be sidestepped because no novel genes would be inserted into the plant. Regulatory hurdles would evaporate because the engineered plants wouldn't produce any novel protein.

Unfortunately, the idea of 'one short RNA knocks out one gene' is even more simplistic than the 'one gene one protein' paradigm.

Cross-talk between short RNAs is even greater than cross-talk between genes. Short RNAs not only block single gene expression, but have a wide-ranging regulatory role including interacting with other short RNAs, and the ability to alter their function in response to environmental factors. They are implicated in cellular dysfunction and disease processes, and can permanently (heritably) alter DNA expression. At the cellular level, short RNAs modulate critical changes such as differentiation into specialised cells, natural cell death, proliferation, immune responses and tissue identity (their role in cancer development is inescapable). Most worrying, short RNAs are increasingly being shown to play a major part in cell communication. This they can do because, unlike the protein-blueprint RNA which is rapidly degraded, short RNAs can be stabilised by molecular configuration and by packaging within a protective membrane. Past experience of how regulators have handled food plants transformed to produce RNA does not inspire confidence that they will take safety considerations seriously.

Historically, regulators waved through the first GMO crop, a DNA-transformed tomato, with little attention to safety. The 'FlavSavr' tomatoes were created using 'antisense' gene technology in which no novel protein is generated. Antisense technology is a type of RNA interference, but doesn't involve short RNA. It might, nevertheless, be used as a precedent to by-pass all meaningful safety testing.

Industry and regulators might also try to cling to the assumptions that short RNAs don't constitute a food safety concern because they will be destroyed by cooking and digestion, and because they will be species-specific and, therefore, inactive in the 'wrong' organisms.

However, a team of scientists has just blown the above assumptions well and truly apart.

Experiments using animal models and, where possible, human subjects has found that dietary short RNAs not only survive cooking and digestion, but are absorbed, circulate in the blood stream and enter mammalian tissues (including milk) and vital organs. Some 30 species of short RNA were consistently present in human blood and maintained at elevated levels. The research team also demonstrated that at least two common plant short RNA species are active in mammalian liver cells where they alter fat metabolism to reduce low-density lipoproteins (considered 'bad' lipids associated with cardio-vascular disease). In other words, short RNAs from plants are not passive, transient dietary materials, but are emerging as routine components of the blood serving important physiological purposes.

Recognising the possibility that short RNAs are an essential micro-nutrient, the authors expressed their confidence that “other people will find more exogenous plant microRNAs that can pass through the (gastro-intestinal) tract and also have effects on the host physiology”.

OUR COMMENT

The demonstrated health-promoting effects of the short RNAs are likely to be the tip of a very large nutritional iceberg. The demonstration of disease-promoting effects of short RNAs may not be far behind (that is, providing scientists are allowed to search for them).

Reportedly, the race is already on between the crop biotech giants to produce commercial insect-resistant crops using short RNA technology.

The range of potential harmful effects from any artificial short RNAs in our food as appalling.

Besides cell dysfunction and cancer, short RNAs have the potential to leave a permanent “imprint on the genetic map of the human race” (Auer).

Although they are small molecules, short RNAs are subject to mutation and variation in structure which could have wide-ranging effects on health and disease. Their presence in food can only be tracked using sophisticated and expensive tests.

If you value your health don't be conned into the notion that engineered DNA is OK so long as it isn't a gene: it could be much, much worse.


SOURCES
  • Scott Kilman, Monsanto Corn Plant Losing Bug Resistance, Wall Street Journal, 29.08.11
  • Cristina Luiggi, Plant RNAs Found in Mammals, The Scientist, 20.09.11
  • Carol Auer and Robert Frederick, 2009, Crop improvement using small RNAs: applications and predictive ecological risk assessment, J. Tibtech
  • Lin Zhang et al., 2011, Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA, Cell Research
  • Belinda Martineau, First Fruit, 2001, ISBN 0-07-140027-3

2 comments:

  1. Thank you for sharing this information.
    It will really helpful to solve my confusion

    Process $ Chemical Engineering

    ReplyDelete
  2. Really interesing, a new point of view of dangers of GM stuff.

    ReplyDelete

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