DNA throws wobblies

April 2011

There is only one predictable thing about transgenic organisms: they will change with time.

However, the way in which they will change is entirely unpredictable.

All GMOs are subject to inescapable destabilising influences. These come from intrinsic structural qualities of their artificial DNA, and, from the natural life-processes within which the artificial DNA must operate. Both act to alter the carefully manufactured DNA cassette, and once destabilised, anything can happen.

The DNA prepared for insertion into cells typically consists of a gene designed to generate the required protein with a 'promoter' at the front end and a 'terminator' at the rear end. The 'promoter' is vital because the artificial gene, outside any natural context to trigger its activity, simply won't do anything: the promoter functions as an independent 'ON' plus 'full-throttle ahead' switch, to make the transgene generate maximum amounts of the required protein. The 'terminator' is vital because it tells the gene where it ends: without it, the DNA downstream from the gene will become part of it and alter the protein produced, for example, to add bits on, remove or rearrange sections, or to change its three-dimensional structure (on which protein function depends).

This functional DNA unit is commonly sandwiched between two 'sticky ends' of DNA designed to enable the whole construct to invade and attach itself to the host genome.

So what's the problem?

Basic problem number one: DNA sequences constructed very easily in a test-tube will tend to carry on, just as easily, re-constructing themselves.

This tendency is exacerbated by many factors. For example, there are known weak points within the DNA construct which are prone to breaking and re-joining in novel ways (one such weak point lies in the most commonly used promoter, the 'Cauliflower Mosaic' viral promoter). Add to this, the lack of any natural connection to the cell's repair mechanisms. The latter are very efficient. They constantly stabilise the organism's own DNA, but may deal differently with artificial DNA.

Basic problem number two: DNA designed to move and invade will tend to carry on moving and invading.

Artificial DNA is known to preferentially attach to sequences of DNA in the host genome which have some similarity in structure to its own. In the fluid state of a living cell, all parts of the genome are in intimate contact with all other parts: there may be no shortage of triggers for unstable parts to rearrange themselves or to move en masse elsewhere. They may even move out of the host organism altogether.

The 'sticky ends' of the DNA construct are routinely copied from pathogenic micro-organisms or viruses (the most commonly used one comes from a bacterium which invades plant cells and causes tumours to form). The artificial invader lodges in the host genome because it has found a site there which it can easily invade. By the same token, it will just as easily move off and invade another site.

The scenario indicated by these two problems alone is of ever-mutating fragments of artificial DNA moving around in the living world, and causing havoc.

There are many more layers of complexity which can be added in. For instance, the presence of multiple stacked transgenes, tissue-specific sections, completely artificial DNA 'glue', left-over bacterial bits from earlier stages in transgene production, marker genes etc.

Every transgenic organism investigated so far has been found to have scrambled DNA both in the artificial construct itself and in the adjacent host DNA, or even, in distant areas of the genome, plus altered gene expression. The vast majority of GMOs have not been investigated at all, even the ones already in our food chain.

The implications of all this for the safety and reliability of our food supply are huge:

• if the transgene changes, the protein it generates will change
• if the 'terminator' DNA is lost, a completely new protein will form
• if the 'promoter' DNA goes A.W.O.L., it will act on any DNA it lands beside to produce an abundance of an unwanted protein or even some very unusual novel material.
• a GMO under stress will be more susceptible to DNA changes: since levels of environmental stress vary from year to year, last years 'safe' GM crop may become this year's health hazard.

The implications for agriculture are equally huge:

• GMOs which breed true are unlikely to be the norm: the sole source of pure, albeit very expensive, GM seed can only ever be the biotech industry
• while regulators focus only on the effects of genetic contamination from the flow of whole, functional artificial genes, the bigger danger is ignored: fragmented artificial DNA constructs will contaminate non-GM crops and disrupt them in unknown ways
• since the identification of genetic pollution requires the DNA sequence to be known before an appropriate chemical 'probe' can be constructed, fragments of artificial DNA constructs will be difficult, or impossible, to trace.

The implications for the wider environment are unthinkable. Man-made DNA shuffling around inside crops and inside the occasional weed will also be shuffling around inside this soil, inside bacteria and inside viruses. Since horizontal gene transfer and recombination is the main route for generating new pathogens, the man-made bits of DNA (promoter, terminators, sticky bits etc.) shuffling around the environment could become the main route for who knows what disease.

And then there's the added scary possibility of horizontal DNA transfers into you.

The biotech industry insists that its products are safe and predictable because “genetic modification of crops has become a precise science in recent years” and “GM plant technology is now about doing something well-defined”. However, given the extent of instability intrinsic to any artificial DNA construct and its transgenic host, you can make up your own mind whether it is reasonable to believe this.

Ask yourself:

Is GM safety just a matter of waiting until the technology is perfected to produce precise, well-defined crops for our food?

Or, is the very concept of GM fundamentally flawed?

(This article is adapted from an article which first appeared on GM-free Scotland in March 2008. View an archived copy of the article here.)

Sources

• Colin Barras, The GM potato war, Daily Telegraph, 23.11.07
• Transgenic Lines Unstable hence Illegal and ineligible for Protection, Institute of Science in Society Press Release 17.03.08 www.i-sis.org.uk/transgenicLinesUnstable2.php
• AK Wilson et al., Transformation-induced Mutations in transgenic Plants: Analysis and Biosafety Implication, Biotechnology and Genetic Engineering Reviews, 23 December 2006, pp209-37, www.bioscienceresource.org.docs/BSR-2-BGERvol23.pdf
• Horizontal Gene Transfer from GMOs Does Happen, Institute of Science in Society Press Release 10.03.08 www.i-sis.org.uk/horizontalGeneTransfer.php