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