Genetic firewalls

June 2015
Photo Creative Commons
Proteins are made up from chains of standard building blocks termed 'amino-acids'. Amino acids can react with each other to form a chain, and have a side-arm which can be any one of some 24 specific molecules each having its own particular properties. The important properties of the amino-acid side-arms include, for example, size, shape, reactivity, bonding capacity and electrical charges. It's the specific sequence of amino-acid side-chains which dictate the properties of the protein they make up, for example, how it folds into a 3-dimensional shape, what chemicals or chemical groups it can react with or bind to, how easily it can be digested, and its toxicity.
Chemical engineers can create an almost infinite variety of artificial amino-acids by attaching novel side-arms. Unnatural amino-acids aren't any use to natural living organisms, but biotech scientists have hit on them as a basis for terminator technology for their genetically modified organisms (GMOs). The principle is that an essential enzyme (see below) is cleverly redesigned to incorporate a novel amino-acid while still preserving its enzymic function. 

Note. Enzymes are biological catalysts which drive all life-processes in cells; they are large proteins designed to latch onto the reacting substances.
A GMO is then created with a novel gene coding for this novel enzyme. Because the organisms can’t survive without the novel enzyme and can't generate the novel enzyme unless they've been fed the humanly-produced amino-acid, humans have the power of life or death over them.
Earlier this year, two papers were published by American University scientists describing how they had created GM bacteria incorporating such genetic 'firewalls' to contain them. The bacteria are not only dependent on the supply of a novel amino-acid, but have multiple re-coded genes to generate multiple re-coded essential enzymes scattered around their genome. This tactic effectively eliminates the chance of the bacteria reverting to uncontrollable wild-type by horizontal gene transfer from another bacterium, or by mutation of the novel genes, because so many changes would have to occur in parallel.
(COMMENT. The novel bacteria also seem to exhibit a disruption to their mechanism for protein breakdown, which prevents the GMOs from feeding off artificial amino-acids derived from dead relatives in the culture medium around them.)
GM bacteria are being increasingly used in industry to generate chemicals, pharmaceuticals and fuels, and for bioremediation of polluted environments. As the authors point out, the value of their terminator technology will lie in the secure containment of industrial- and environmental-scale bacterial cultures.
In a BBC radio interview, another goal of this line of research was revealed: to mollify anti-GM campaigners concerned about rampant GMOs in their environment. Indeed, the media were very ready to provide the two papers with good coverage. This included a repeat performance of early PR which spoke of "tweaking" DNA, and which seeded confusion between conventional breeding and the direct molecular manipulations of GM. Of course the claimed (but non-existent - see Heinemann) "cheaper seeds, diminishing need for pesticides and higher yield" of GM crops were duly trotted out. 
Much in evidence was an effortless flow from the genetic transformation of a common bacterium (easily achieved by both sets of scientists) to the possibility of a similar terminator technology in higher plants.
The works were hailed as a major step in creating GMOs which will perform an important task and then "die without trace"
Die without trace? Hmmm.
Weird proteins which the GM organisms itself may have problems degrading, and which the environmental microbes Nature uses to decompose matter once the living have finished with it, will tend to hang around long after the GMO itself has gone. Die yes, but without trace, why should they?
Strange that none of the scientists nor their peer reviewers nor the science journalists reporting their work noticed that the headings of both papers refer to "organisms" instead of what they were actually working on which were "bacteria". Setting the stage, perhaps, for confusion about how a technology easily applied to bacteria could flow seamlessly into organisms as complex as higher plants?
The novel amino-acid chosen for development of the terminator technology was selected because it's not toxic. But, what of the novel proteins it's incorporated into? Or any novel changes in the biochemical reactions the novel enzyme participates in?
This terminator technology will only be viable for very high value products because the synthetic amino-acids so far developed cost anything from over $3 per litre of bacterial culture to nearly $300: commercial production would be in the region of thousands of litres. Even if GM plants with the necessary re-coded enzymes and genes could be created, it would be unrealistically expensive to supply the novel amino-acids they would need to live. 
Artificial amino-acids in an open field sound like a serious pollution problem, and also very like a recipe for weird microbes to evolve to make use of the weird proteins.
Nature uses only 24 amino acids to form the protein bases for every one of its uncountable life-forms on the planet. This isn't because Nature lacks imagination or technical flexibility. It's because in a sustainable world all the components of all living organisms must cycle and recycle through the system: a weird protein is an unhealthy dead-end.
Are these GMOs, complete with their super-effective multiple terminator technology, mollifying you into believing they can't cause an environmental or health problem?
  • Daniel J. Mandell, et al., 2015, Biocontainment of genetically modified organisms by synthetic protein design, Nature
  • Alexic J. Rovner, et al., 2015, Recoded organisms engineered to depend on synthetic amino acids, Nature
  • Monte Morin, Creating a 'genetic firewall' for GMOs, Science Now 21.01.15
  • Ian Sample, Scientists create GM organisms reliant on artificial compounds for survival, Guardian 21.01.15
  • Why GM is not the natural solution for future farming, GM Watch 5.02.15
  • Adam Rutherford, Why GM is the natural solution for future farming, Guardian, 31.01.15
  • Jack A. Heinemann, et al., 2014, Sustainability and innovation in staple crops production in the US Midwest, International Journal of Agricultural Sustainability 12:1

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