Genes on the move

News archive - December 2010

What do Agrobacterium and human beings have in common? One's a soil bacterium and the other's a primate with a very large brain: the scope for sharing anything seems limited. However, both carry out genetic transformations of other life-forms to provide food for themselves.

Put more accurately, the genetic engineers with the big brains have hijacked the gene transfer mechanism of their microscopic counterparts to provide human food.

Well done, humans!


But, our cleverness begs a serious question: can Agrobacterium turn the tables, and hijack human cells, transforming them to provide novel food for itself?

The question of horizontal gene transfer (see SCIENCE - Horizontal gene transfer) from GM food into other life-forms has been considered by regulators, albeit half-heartedly. Attention has always focused on antibiotic resistance genes which are created and inserted as a technical trick to identify which cells have been successfully transformed. This problem can be solved by avoiding use of such genes in the first place, or, by removing them post-transformation (both perfectly possible, just less convenient). Early on, the UK Food Standards Agency commissioned a study on the possibility of gene transfer from two common gut microbes into human gut cells, but found no cause for concern. The view of regulators is that we are exposed to DNA from plants, bacteria and viruses all the time in our food, and so GM DNA isn't going to cause any additional problem.

However, no one's been factoring in Agrobacterium.

Agrobacterium is a specialised plant pathogen. It has the ability to genetically transform many hundreds of plant species to form galls (plant 'tumours') which provide a unique chemical and environmental habitat for the bug. Infection is triggered by wounded plant tissue: the wound exudes plant hormones which attract Agrobacterium and primes it to take control of the plant cells by switching on the genes it needs to insert its tumourigenic DNA.

The regulators' view is that a plant pathogen can't present a problem to animals (including livestock and humans).

To transform plants, genetic engineers replace the gall-causing DNA in Agrobacterium with engineered DNA of their choosing. When plant cells are exposed to the re-jigged and primed Agrobacterium, the bugs obligingly ferry the novel DNA into the cells and insert it into the the plants own DNA. The plant cells are then treated with antibiotics to kill off the bugs before being propagated into whole crops for eventual commercial release. All this is, of course, carried out in laboratories and greenhouses.

So, what's the problem?

Problem number one is that not all Agrobacterium are successfully removed: some will remain on the GM plant and be passed on to future generations. One study, on GM poplars, suggested that 80% of the trees were still harbouring the Agrobacterium used to transform them.

This means that GM crops transfected using Agrobacterium can form a reservoir in the field, not only of artificial DNA, but of artificial DNA plus the vector needed to efficiently insert novel genes into many other plants.

Problem number two is that Agrobacterium-mediated gene insertion is not limited to higher plant cells, but can extend to animal cells. A study using cultured human cervical cancer, kidney and nerve cells demonstrated that Agrobacterium, could insert genes into all of them. Transformation was observed whether or not the bacteria had been primed, and the process of insertion was unexpectedly found to be identical to that for transforming plants cells.

Problem number three is that Agrobacterium-mediated gene insertion can extend to fungi. Since fungi form a large and vital part of the soil ecosystem, and can spread with the greatest of ease, horizontal gene transfer into them is not good news. A study just published has shown that the conditions prevailing at a plant wound-site were sufficient for Agrobacterium to genetically transform a fungus.

Agrobacterium is also known to be able to genetically transform yeast. Like fungi, yeast has an unsurpassed ability to spread, and is a well-known opportunistic pathogen.

What could all these unnatural and unprecedented horizontal gene transfers lead to? The most likely scenario is that a previously unknown, highly atypical, disease emerges which invites in a range of opportunistic pathogens and is ignored for decades because there's no test available for a definitive diagnosis. At worst, we would have little or no immunity to the novel organism, and this would be exacerbated by genetic instability caused by to the presence of the engineered DNA which would make the pathogen fast-changing.

Suspicion has already fallen on an “unknown skin disease” (also referred to as the 'silent' or 'hidden' US epidemic, or inaccurately as 'Morgellons Syndrome'). This disease presents with skin lesions, joint pain and neurological difficulties and is thought to affect over 10,000 individuals in America. The US Center for Disease Control (CDC) has now recognised the epidemic and has initiated investigations into it, but Europe's medical community has not reacted.

Theories about the aetiology of the disease include nano-particles, UFOs, delusional parasitosis, and self-harm. However, there is some evidence of a common history in affected individuals, both of contact with soil and of the presence of Agrobacterium in skin lesions, which has raised interesting possibilities of a GM connection.

OUR COMMENT

The jury's still out regarding the 'unknown skin disease', but it provides a perfect lesson. Have a look at the horrific pictures posted on the Morgellons Research Organisation website. Huge suffering will arise from any new disease before the medical profession begins to recognise it for what it is, and before any research into a cure or symptomatic relief can even begin.

If the 'unknown skin disease' is an evolving Agrobacterium-induced GMO, a cure might be impossible. If the 'unknown skin disease' isn't a GMO, the next 'unknown disease' might well be.

SOURCES

• Agrobacterium & Morgellons Disease, A GM Connection? Institute of Science in Society Report, 28.04.08
• Possible new twist in GM safety debate, University of Bristol Press Release, October 2010
• Tzvi Tzfira and Vitaly Citovsky, 2003, The Agrobacterium-Plant Cell Interaction. Taking Biology Lessons from a Bug, Plant Physiology, November, 133
• Knight C. J., et al., 2010, Investigation Agrobacterium-Mediated Transformation of Verticillium albo-atrum on Plant Surfaces, PLoS ONE 5:10
• Kunic T., et al., 2001, Genetic transformation of HeLa cells by Agrobacterium, PNAS 13.02.01, 98:4
• Minsheng Y., et al., 2006, Survival and escape of Agrobacterium tumefaciens in triploid hybrid lines of Chinese white poplar transformed with two insect-resistant genes, Ecological Society of China, November, 26:11
• Marc Neumann, Introduction to the “Morgellons Syndrome” (2007 – Revised 2010), www.morgellons-research.org
• Netherwood, Technical report on the FSA project “Evaluating the risks associated with using GMOs in human foods, FSA project GO 10008.