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Unintended Effects of Genetic Manipulation
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Posted: September 2014

Why GM Bacteria Haven’t Succeeded in the Real World:
It’s the Context, Not Only the Genes

The paradigmatic idea behind genetic modification is that genes control the formation of an organism’s characteristics, so that by introducing new genes you can alter the organism and it takes on new characteristics. In the 1980s, when genetic modification of organisms was beginning, there were great hopes that GM bacteria—“superbugs”—could be used to break down an array of pollutants in the environment. Many such GM bacteria have been developed in the laboratory, but with few exceptions, the real world applications have not materialized.

The main problem is that the engineers did not reckon with the fact that organisms are not just the consequence of genetic instructions and that the whole organism is actively involved in relating to the complex and changing context of the natural environment. The idea that one could, through the addition of a few genes, “manufacture” and control bacteria in real-world environments was naive.

Biotechnologists have been able to develop genetically modified bacteria that break down an astounding array of chemicals that would otherwise be very resistant to degradation. There are GM bacteria that break down camphor, octane, salicylate, naphthalene, various petroleum components, chloroaromatic compounds, and more. The problem turned out to be that, while GM bacteria performed well under laboratory conditions, they did not do well in complex real-world environments: “only in very few cases has the use of a GMO turned out to be much better than the performance of its natural, non-manipulated counterpart” (Cases and de Lorenzo 2005).

One important reason for this has been the choice of bacteria: “the strains and bacterial species that most frequently appear in traditional [laboratory] enrichment procedures are not the ones performing the bulk of biodegradation in natural environments—and may not even be good as bioremediation mediators” due to some of their physiological characteristics (Cases and de Lorenzo 2005). As Victor de Lorenzo, head of the Systems and Synthetic Biology Program at the National Center for Biotechnology in Spain, recently wrote (de Lorenzo 2014):

Changing the instructions (the DNA) is not sufficient for ensuring that the whole biological system duly obeys the orders coming from [DNA]. ... It seems that the physiology of the host, of which metabolism is the key component, has a say in whether the directions from DNA are to be implemented or not.

In addition, the heterogeneous texture of natural bacterial environments leads to the development of distinct populations that differ genetically from one another and that “diverge quickly from the original inoculum” (2005). The bacteria containing the transgenes may disappear altogether in this process. Even in controlled supportive environments there is the phenomenon of “catalytic fatigue” in which the activity of the introduced gene decreases over time (2014).

Summing up the difficulties in using GM bacteria as a means to degrade pollutants in the environment, Cases and de Lorenzo write in their review article (2005):

We have plenty of genetic tools—yet we are still far from dominating the construction of GMOs for in situ [that is, in natural environments] bioremediation. What then appeared to be a simple DNA cut and paste exercise appears now framed within a complex network of intracellular and intercellular metabolic and regulatory interactions that cannot be tackled with traditional genetic approaches.

All this shows how problematic the gene-centered paradigm that rules genetic engineering is. The apparent foundations of this paradigm have for some time now been crumbling, based on the plethora of findings in basic research in molecular biology (see the Biology Worthy of Life project). But genetic technologies are still by and large based on it. While the failure of the approach shows itself most drastically in bacteria, which are extremely context sensitive and physiologically adaptive, plants and animals are also flexible and context-sensitive—even when they are viewed and manipulated as genetic machines.

de Lorenzo, V. (2014). “From the Selfish Gene to Selfish Metabolism: Revisiting the Central Dogma,” Bioessays vol. 36, pp. 226-35. doi:10.1002/bies.201300153

Cases, I. and V. de Lorenzo (2005). “Genetically Modified Organism for the Environment: Stories of Success and Faliure and What We Have Learned From Them,” International Microbiology vol. 8, pp. 213-22.

Copyright 2014 The Nature Institute.

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